WO2024060326A1 - Antibody combination and system for detecting prognosis of nasopharyngeal cancer, and use - Google Patents
Antibody combination and system for detecting prognosis of nasopharyngeal cancer, and use Download PDFInfo
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- 206010061306 Nasopharyngeal cancer Diseases 0.000 title claims abstract description 41
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
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Definitions
- the invention belongs to the field of biomedicine, and specifically relates to an antibody combination, system and application for predicting the prognosis of nasopharyngeal cancer.
- Nasopharyngeal carcinoma is a unique head and neck tumor that is common in southern China and is also known as "Guangdong tumor.” Nasopharyngeal carcinoma occurs in the nasopharynx, has an insidious onset, and is usually diagnosed in the middle or late stages.
- nasopharyngeal cancer is closely related to Epstein-Barr virus infection.
- EB virus infection is very common in the population. It is reported that more than 95% of adults around the world carry EB virus.
- Many studies have shown that EB virus is related to nasopharyngeal cancer, gastric cancer, malignant lymphoma and other tumors. For this reason WHO classifies it as a class I carcinogen.
- EBV Almost all nasopharyngeal cancer patients are EBV positive. After EBV infects the host, it enters the latent infection phase and the replication and division phase.
- the latent infection phase mainly expresses EBV-related nuclear antigen and latent membrane protein
- the cleavage and replication phase mainly expresses the virus. capsid antigen, early intracellular antigen, early membrane antigen and late-associated antigen.
- EB virus lurks in nasopharyngeal carcinoma tumor cells. It is activated from the latency period into the lysis cycle and releases a large number of virus particles, which may be recognized by antibodies secreted by surrounding plasma cells. Therefore, antibodies in nasopharyngeal carcinoma can not only recognize viral particles and eliminate EBV-positive tumor cells, but also have the potential to predict disease status.
- the traditional method is to detect EB virus-related antibody titers in the peripheral blood of patients with nasopharyngeal carcinoma, which is different from the activity status of EB virus in tumors. Direct detection of antibody titers in tumor tissue may better reflect the disease state.
- one object of the present invention is to provide an antibody or antibody combination for predicting the prognosis of nasopharyngeal carcinoma.
- Another object of the present invention is to provide a system for predicting the prognosis of nasopharyngeal carcinoma.
- Another object of the present invention is to provide the application of the antibody combination for predicting the prognosis of nasopharyngeal carcinoma.
- the present invention provides an antibody combination for detecting the prognosis of nasopharyngeal carcinoma, the antibody combination includes at least one of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4.
- the above eight antibody components can be used to predict the prognosis of nasopharyngeal cancer alone or in any combination.
- the present invention also provides the use of the antibody combination in preparing a reagent for determining the prognosis of nasopharyngeal carcinoma.
- the present invention also provides the use of reagents for quantifying the antibody combination of the present invention in the preparation of nasopharyngeal cancer prognosis determining reagents.
- the reagent used to quantify the antibody combination of the present invention is a reagent for quantifying antibody heavy chain mRNA or protein.
- the reagent can also be other reagents, chips or other methods that can reflect the expression level of marker mRNA or protein.
- the present invention also provides a system for predicting the prognosis of nasopharyngeal cancer, which includes:
- Antibody heavy chain quantification device which is used to determine the expression amount of the heavy chain of the antibody combination according to claim 1;
- a data analysis device that calculates and determines the prognosis of nasopharyngeal cancer based on the expression amount of the antibody heavy chain
- a result output device is used to output the calculated prognostic result.
- the expression level can be the expression level determined by different methods, preferably the expression level after dimensionless processing, to facilitate data analysis and processing.
- the antibody heavy chain quantitative device includes reagents, chips, detection devices, and kits for quantitatively detecting marker mRNA or protein expression levels.
- the expression level of the antibody heavy chain is obtained by quantifying the gene mRNA or protein expression level of the antibody heavy chain.
- reagents for quantitatively detecting marker mRNA at the gene level include, but are not limited to, expression chips, mRNA sequencing devices, qPCR gene detection devices, and Nanostring technology gene detection devices.
- Methods for quantifying marker proteins at the protein level include, but are not limited to, enzyme-linked immunoreaction (ELISA), radioimmunoassay (IRA), immunohistochemical staining, Western blotting, electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS) /MS) etc.
- ssGSEA Gene Set Enrichment Analysis
- the expression level of IGHD when the expression level of IGHD is lower than 2.985, it is judged as high risk, and when it is higher than 2.985, it is judged as low risk.
- IGHAl when the expression level of IGHAl is lower than 756.34, it is judged to be high risk, and when it is higher than 756.34, it is judged to be low risk.
- IGHA2 when the expression level of IGHA2 is lower than 560.23, it is judged to be high risk, and when it is higher than 560.23, it is judged to be low risk.
- IGHG1 when the expression level of IGHG1 is lower than 9570.435, it is judged to be high risk, and when it is higher than 9570.435, it is judged to be low risk.
- IGHG2 when the expression level of IGHG2 is lower than 560.23, it is judged to be high risk, and when it is higher than 560.23, it is judged to be low risk.
- IGHG3 when the expression level of IGHG3 is lower than 558.075, it is judged to be high risk, and when it is higher than 558.075, it is judged to be low risk.
- IGHG4 when the expression level of IGHG4 is lower than 437.92, it is judged to be high risk, and when it is higher than 437.92, it is judged to be low risk.
- the present invention can predict the clinical prognosis of nasopharyngeal cancer patients, help implement individualized treatment for patients, and improve survival benefits.
- Figure 1 shows the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in tumors in patients with nasopharyngeal carcinoma who were divided into high and low groups according to the EB virus titer in their plasma ( Above, A); According to the intratumoral EBV titer of nasopharyngeal cancer patients, the patients were divided into high and low groups. The expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in the tumor. (below, B).
- Figure 2 shows that NPC patients are divided into a high group and a low group according to the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4, and the Kaplan-Meier (KM) survival curve analysis shows the difference in progression-free survival between the two groups of patients; wherein, (A) IGHM, (B) IGHD, (C) IGHA1, (D) IGHA2, (E) IGHG1, (F) IGHG2, (G) IGHG3, (H) IGHG4.
- nasopharyngeal cancer tumor tissue samples were collected through nasopharyngoscopy before treatment, and mRNA transcriptome sequencing was performed on each sample to obtain the transcriptome of each sample. Gene expression profiling.
- EBV copy number in the peripheral blood and tumor tissue of these 59 patients was measured, and the patients were divided into two groups, high and low EBV, using 1000 copies/mL and the median value as the limits respectively.
- Figure 1 shows the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in tumors in patients with nasopharyngeal carcinoma who were divided into high and low groups according to the EB virus titer in their plasma ( Above, A); According to the intratumoral EBV titer of nasopharyngeal cancer patients, the patients were divided into high and low groups. The expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in the tumor. (below, B).
- the left side is a patient with high EBV (i.e., EBV titer ⁇ 1000 copies/mL)
- the right side is a patient with low EBV (i.e., EBV titer ⁇ 1000 copies/mL)
- the ordinate is the value after TPM (Transcripts Per Million) normalization (+0.001) and logarithm.
- ROC receiver operating characteristic
- the eight antibody heavy chains IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 can be used as prognostic factors in patients with nasopharyngeal carcinoma and have good prognostic value.
- the following criteria can be used: when the expression level of IGHM is lower than 182.125, it is judged to be high risk, and when it is higher than 182.125, it is judged to be low risk; when the expression level of IGHD is lower than 2.985, it is judged to be high risk, and when it is higher than 2.985, it is judged to be high risk.
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Abstract
Provided is an antibody combination for detecting the prognosis of nasopharyngeal cancer. The antibody combination comprises at least one of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4. Provided are use of the antibody combination and a system for predicting the prognosis of nasopharyngeal cancer. By determining the expression levels of heavy chains of the antibody combination, clinical prognosis prediction can be carried out on a patient with nasopharyngeal cancer, which facilitates the implementation of individualized treatment and the improvement of a survival benefit.
Description
本发明属于生物医药领域，具体涉及一种用于预测鼻咽癌预后的抗体组合、***及应用。The invention belongs to the field of biomedicine, and specifically relates to an antibody combination, system and application for predicting the prognosis of nasopharyngeal cancer.
鼻咽癌是一种独特的头颈部肿瘤，好发于华南地区，也被称之为“广东瘤”。鼻咽癌发病于鼻咽部，起病隐匿，诊断时多为中晚期。Nasopharyngeal carcinoma is a unique head and neck tumor that is common in southern China and is also known as "Guangdong tumor." Nasopharyngeal carcinoma occurs in the nasopharynx, has an insidious onset, and is usually diagnosed in the middle or late stages.
目前鼻咽癌的发病机制尚未完全明确，国内外各项研究均表明鼻咽癌与EB病毒感染密切相关。EB病毒在人群中的感染非常普遍，据报道全球约有95％以上的成年人携带有EB病毒，多项研究表明EB病毒与鼻咽癌、胃癌、恶性淋巴瘤等多种肿瘤相关，为此WHO将其归为I类致癌物。几乎所有的鼻咽癌患者均为EB病毒阳性，EB病毒感染宿主后，进入潜伏感染期和复制***期，其中潜伏感染期主要表达EB病毒相关核抗原和潜伏膜蛋白，裂解复制期主要表达病毒壳抗原、早期细胞内抗原、早期膜抗原及晚期相关抗原。在鼻咽癌肿瘤组织内EB病毒潜伏在鼻咽癌肿瘤细胞内，从潜伏期被激活进入裂解周期，释放大量的病毒颗粒，可能被周围浆细胞分泌的抗体所识别。因此，鼻咽癌内的抗体既可以识别病毒颗粒，清除EB病毒阳性的肿瘤细胞，也具有潜在预测疾病状态的能力。At present, the pathogenesis of nasopharyngeal cancer has not been fully understood. Various domestic and foreign studies have shown that nasopharyngeal cancer is closely related to Epstein-Barr virus infection. EB virus infection is very common in the population. It is reported that more than 95% of adults around the world carry EB virus. Many studies have shown that EB virus is related to nasopharyngeal cancer, gastric cancer, malignant lymphoma and other tumors. For this reason WHO classifies it as a class I carcinogen. Almost all nasopharyngeal cancer patients are EBV positive. After EBV infects the host, it enters the latent infection phase and the replication and division phase. The latent infection phase mainly expresses EBV-related nuclear antigen and latent membrane protein, and the cleavage and replication phase mainly expresses the virus. capsid antigen, early intracellular antigen, early membrane antigen and late-associated antigen. In nasopharyngeal carcinoma tumor tissue, EB virus lurks in nasopharyngeal carcinoma tumor cells. It is activated from the latency period into the lysis cycle and releases a large number of virus particles, which may be recognized by antibodies secreted by surrounding plasma cells. Therefore, antibodies in nasopharyngeal carcinoma can not only recognize viral particles and eliminate EBV-positive tumor cells, but also have the potential to predict disease status.
传统的方法是检测鼻咽癌患者外周血中的EB病毒相关抗体滴度，与肿瘤内EB病毒的活动状态有所差异，直接检测肿瘤组织中的抗体滴度可能更好地反映疾病状态。The traditional method is to detect EB virus-related antibody titers in the peripheral blood of patients with nasopharyngeal carcinoma, which is different from the activity status of EB virus in tumors. Direct detection of antibody titers in tumor tissue may better reflect the disease state.
发明内容Contents of the invention
针对以上要解决的技术问题，本发明的一个目的是提供一种用于预测鼻咽癌预后的抗体或抗体组合。In view of the above technical problems to be solved, one object of the present invention is to provide an antibody or antibody combination for predicting the prognosis of nasopharyngeal carcinoma.
本发明的另一个目的是提供一种用于预测鼻咽癌预后的***。Another object of the present invention is to provide a system for predicting the prognosis of nasopharyngeal carcinoma.
本发明的再一个目的是提供所述用于预测鼻咽癌预后的抗体组合的应用。Another object of the present invention is to provide the application of the antibody combination for predicting the prognosis of nasopharyngeal carcinoma.
为实现上述目的，本发明提供了一种用于检测鼻咽癌预后的抗体组合，所述抗体组合包括IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4中的至少一种。To achieve the above object, the present invention provides an antibody combination for detecting the prognosis of nasopharyngeal carcinoma, the antibody combination includes at least one of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4.
上述八种抗体成分，既可以单独用于预测鼻咽癌的预后，也可以多种任意组合用于预测鼻咽癌的预后。The above eight antibody components can be used to predict the prognosis of nasopharyngeal cancer alone or in any combination.
另一方面，本发明还提供了所述的抗体组合在制备鼻咽癌预后确定试剂中的应用。On the other hand, the present invention also provides the use of the antibody combination in preparing a reagent for determining the prognosis of nasopharyngeal carcinoma.
另一方面，本发明还提供了用于定量本发明所述的抗体组合的试剂在制备鼻咽癌预后确 定试剂中的应用。On the other hand, the present invention also provides the use of reagents for quantifying the antibody combination of the present invention in the preparation of nasopharyngeal cancer prognosis determining reagents.
优选地，用于定量本发明所述抗体组合的试剂为定量抗体重链mRNA或蛋白的试剂。试剂也可以是其他可反映标志物mRNA或蛋白表达量的试剂、芯片或其他方法。Preferably, the reagent used to quantify the antibody combination of the present invention is a reagent for quantifying antibody heavy chain mRNA or protein. The reagent can also be other reagents, chips or other methods that can reflect the expression level of marker mRNA or protein.
另一方面，本发明还提供了一种用于预测鼻咽癌预后的***，其包括：On the other hand, the present invention also provides a system for predicting the prognosis of nasopharyngeal cancer, which includes:
抗体重链定量装置，其用于确定权利要求1所述的抗体组合的重链的表达量；Antibody heavy chain quantification device, which is used to determine the expression amount of the heavy chain of the antibody combination according to claim 1;
数据分析装置，其基于所述抗体重链的表达量，计算确定鼻咽癌的预后；A data analysis device that calculates and determines the prognosis of nasopharyngeal cancer based on the expression amount of the antibody heavy chain;
结果输出装置，其用于输出计算的预后结果。A result output device is used to output the calculated prognostic result.
优选地，表达量可以是不同方法确定的表达量，优选为无量纲处理后的表达量，方便进行数据分析处理。Preferably, the expression level can be the expression level determined by different methods, preferably the expression level after dimensionless processing, to facilitate data analysis and processing.
在一些实例中，所述抗体重链定量装置包括定量检测标志物mRNA或蛋白表达量的试剂、芯片、检测装置、试剂盒。In some examples, the antibody heavy chain quantitative device includes reagents, chips, detection devices, and kits for quantitatively detecting marker mRNA or protein expression levels.
在一些实例中，通过定量所述抗体重链的基因mRNA或蛋白表达量得到所述抗体重链的表达量。In some examples, the expression level of the antibody heavy chain is obtained by quantifying the gene mRNA or protein expression level of the antibody heavy chain.
在一些实例中，在基因水平上定量检测标志物mRNA的试剂包括但不限于表达芯片、mRNA测序装置、qPCR基因检测装置以及Nanostring技术基因检测装置等。在蛋白水平上定量标志物蛋白的方法包括但不限于酶联免疫反应(ELISA)、放射免疫反应(IRA)、免疫组化染色、蛋白质印迹、电泳、液相色谱-质谱/质谱(LC-MS/MS)等。In some examples, reagents for quantitatively detecting marker mRNA at the gene level include, but are not limited to, expression chips, mRNA sequencing devices, qPCR gene detection devices, and Nanostring technology gene detection devices. Methods for quantifying marker proteins at the protein level include, but are not limited to, enzyme-linked immunoreaction (ELISA), radioimmunoassay (IRA), immunohistochemical staining, Western blotting, electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS) /MS) etc.
在一些实例中，通过定量各成分特征基因mRNA或蛋白表达量，对各成分全部特征基因的mRNA表达量进行单样本基因富集分析(single-sample Gene Set Enrichment Analysis，ssGSEA)，即可计算出各成分的表达量。将不同方法确定的mRNA或蛋白表达量归一化。In some examples, by quantifying the mRNA or protein expression of the characteristic genes of each component, and performing a single-sample Gene Set Enrichment Analysis (ssGSEA) on the mRNA expression of all characteristic genes of each component, it can be calculated The expression level of each component. Normalize the mRNA or protein expression levels determined by different methods.
在一些实例中，所述IGHM的表达量低于182.125时判定为高风险，高于182.125时判定为低风险。In some examples, when the expression level of IGHM is lower than 182.125, it is judged to be high risk, and when it is higher than 182.125, it is judged to be low risk.
在一些实例中，所述IGHD的表达量低于2.985时判定为高风险，高于2.985判定为低风险。In some examples, when the expression level of IGHD is lower than 2.985, it is judged as high risk, and when it is higher than 2.985, it is judged as low risk.
在一些实例中，所述IGHA1的表达量低于756.34时判定为高风险，高于756.34时判定为低风险。In some examples, when the expression level of IGHAl is lower than 756.34, it is judged to be high risk, and when it is higher than 756.34, it is judged to be low risk.
在一些实例中，所述IGHA2的表达量低于560.23时判定为高风险，高于560.23时判定为低风险。In some examples, when the expression level of IGHA2 is lower than 560.23, it is judged to be high risk, and when it is higher than 560.23, it is judged to be low risk.
在一些实例中，所述IGHG1的表达量低于9570.435时判定为高风险，高于9570.435时判定为低风险。In some examples, when the expression level of IGHG1 is lower than 9570.435, it is judged to be high risk, and when it is higher than 9570.435, it is judged to be low risk.
在一些实例中，所述IGHG2的表达量低于560.23时判定为高风险，高于560.23时判定 为低风险。In some examples, when the expression level of IGHG2 is lower than 560.23, it is judged to be high risk, and when it is higher than 560.23, it is judged to be low risk.
在一些实例中，所述IGHG3的表达量低于558.075时判定为高风险，高于558.075时判定为低风险。In some examples, when the expression level of IGHG3 is lower than 558.075, it is judged to be high risk, and when it is higher than 558.075, it is judged to be low risk.
在一些实例中，所述IGHG4的表达量低于437.92时判定为高风险，高于437.92时判定为低风险。In some examples, when the expression level of IGHG4 is lower than 437.92, it is judged to be high risk, and when it is higher than 437.92, it is judged to be low risk.
在一些实例中，也可以采用其他已知的方法来确定具体的风险阀值。In some instances, other known methods may also be used to determine specific risk thresholds.
本发明通过计算八种抗体重链的特征基因或蛋白质的表达量，可以对鼻咽癌患者进行临床预后预测，有助于对患者实行个体化治疗，提高生存获益。By calculating the expression levels of characteristic genes or proteins of eight antibody heavy chains, the present invention can predict the clinical prognosis of nasopharyngeal cancer patients, help implement individualized treatment for patients, and improve survival benefits.
图1示出了根据鼻咽癌患者血浆中EB病毒滴度将患者分为高和低两组中肿瘤内的IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4抗体重链表达量(上图，A)；根据鼻咽癌患者肿瘤内EB病毒滴度将患者分为高和低两组中肿瘤内的IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4抗体重链表达量(下图，B)。Figure 1 shows the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in tumors in patients with nasopharyngeal carcinoma who were divided into high and low groups according to the EB virus titer in their plasma ( Above, A); According to the intratumoral EBV titer of nasopharyngeal cancer patients, the patients were divided into high and low groups. The expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in the tumor. (below, B).
图2示出了根据IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4表达量将NPC患者划分为高组和低组，Kaplan-Meier(KM)生存曲线分析展示了两组患者的无进展生存的差异；其中，(A)IGHM，(B)IGHD，(C)IGHA1，(D)IGHA2，(E)IGHG1，(F)IGHG2，(G)IGHG3，(H)IGHG4。Figure 2 shows that NPC patients are divided into a high group and a low group according to the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4, and the Kaplan-Meier (KM) survival curve analysis shows the difference in progression-free survival between the two groups of patients; wherein, (A) IGHM, (B) IGHD, (C) IGHA1, (D) IGHA2, (E) IGHG1, (F) IGHG2, (G) IGHG3, (H) IGHG4.
为了能够更清楚地理解本发明的上述目的、特征和优点，下面结合附图和具体实施方式对本发明进行进一步的详细描述。本领域技术人员应该明了，所述实施例仅仅是帮助理解本发明，不应视为对本发明的具体限制；下述实施例中所使用的测序和分析方法如无特殊说明，均为常规方法。In order to more clearly understand the above objects, features and advantages of the present invention, the present invention will be described in further detail below in conjunction with the accompanying drawings and specific embodiments. Those skilled in the art should understand that the above examples are only to help understand the present invention and should not be regarded as specific limitations of the present invention; the sequencing and analysis methods used in the following examples are all conventional methods unless otherwise specified.
下面将结合具体实验进一步阐述本发明，应理解，以下内容仅用于说明本发明而不用于限制本发明的保护范围。The present invention will be further described below in conjunction with specific experiments. It should be understood that the following content is only used to illustrate the present invention and is not intended to limit the protection scope of the present invention.
实施例Example
对59例于中山大学肿瘤防治中心初治的鼻咽癌患者，在治疗前通过鼻咽镜活检取到鼻咽癌肿瘤组织样本，并对每个样本进行mRNA转录组测序，得到每个样本的基因表达谱。同时检测这59例患者外周血和肿瘤组织的EB病毒拷贝数，分别以1000拷贝/mL和中位值为界限，将患者分为EB病毒高和低两组。For 59 patients with nasopharyngeal cancer who were initially treated at the Sun Yat-sen University Cancer Center, nasopharyngeal cancer tumor tissue samples were collected through nasopharyngoscopy before treatment, and mRNA transcriptome sequencing was performed on each sample to obtain the transcriptome of each sample. Gene expression profiling. At the same time, the EBV copy number in the peripheral blood and tumor tissue of these 59 patients was measured, and the patients were divided into two groups, high and low EBV, using 1000 copies/mL and the median value as the limits respectively.
图1示出了根据鼻咽癌患者血浆中EB病毒滴度将患者分为高和低两组中肿瘤内的IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4抗体重链表达量(上图，A)；根据鼻咽癌患者肿瘤内EB病毒滴度将患者分为高和低两组中肿瘤内的IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4抗体重链表达量(下图，B)。图中，对于每一种抗体，左侧为EB病毒高患者(即，EB病毒滴度≥1000拷贝/mL)，右侧为EB病毒低患者(即，EB病毒滴度＜1000拷贝/mL)，纵坐标为TPM(Transcripts Per Million)均一化(+0.001)和取对数后的值。Figure 1 shows the expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in tumors in patients with nasopharyngeal carcinoma who were divided into high and low groups according to the EB virus titer in their plasma ( Above, A); According to the intratumoral EBV titer of nasopharyngeal cancer patients, the patients were divided into high and low groups. The expression levels of IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains in the tumor. (below, B). In the figure, for each antibody, the left side is a patient with high EBV (i.e., EBV titer ≥1000 copies/mL), and the right side is a patient with low EBV (i.e., EBV titer <1000 copies/mL) , the ordinate is the value after TPM (Transcripts Per Million) normalization (+0.001) and logarithm.
从图1中可以看出，在鼻咽癌患者血浆和肿瘤组织内，相较于EB病毒高患者，IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4抗体重链在EB病毒低患者中表达显著下降(＜0.05)。As can be seen from Figure 1, in the plasma and tumor tissues of nasopharyngeal cancer patients, compared with patients with high EBV, IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 antibody heavy chains are more abundant in patients with low EBV. The expression decreased significantly (<0.05).
结合已发表的88例鼻咽癌患者的转录组数据(GSE102349)，对147例鼻咽癌患者(来自中山大学肿瘤防治中心)的八种抗体重链基因的表达进行分析，利用接受者操作特性(receiver operating characteristic,ROC)曲线寻找每个抗体重链基因表达量的最优解作为界值，将八种抗体IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4重链基因分成高表达组与低表达组，并进行生存分析，探索八种抗体重链基因高表达组对比于低表达组的无进展生存(progression-free survival,PFS)情况。生存曲线采用Kaplan-Meier法绘制，cox检验统计学意义。Combined with the published transcriptome data of 88 nasopharyngeal cancer patients (GSE102349), the expression of eight antibody heavy chain genes in 147 nasopharyngeal cancer patients (from Sun Yat-sen University Cancer Center) was analyzed using receiver operating characteristics. The (receiver operating characteristic, ROC) curve finds the optimal solution for the expression of each antibody heavy chain gene as a boundary value, and divides the eight antibody IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 heavy chain genes into high-expression group and low expression group, and conducted survival analysis to explore the progression-free survival (PFS) of the high expression group of eight antibody heavy chain genes compared with the low expression group. Survival curves were drawn using the Kaplan-Meier method, and Cox tested statistical significance.
结果如图2所示，八种抗体重链的基因高表达时，鼻咽癌患者的预后相比于低表达组患者要更好(P<0.05)。The results are shown in Figure 2. When the genes of eight antibody heavy chains are highly expressed, the prognosis of nasopharyngeal carcinoma patients is better than that of patients in the low expression group (P<0.05).
综合上述结果可以看出，八种抗体重链IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4能够作为鼻咽癌患者的预后因素，具有良好的预后判断的价值。Based on the above results, it can be seen that the eight antibody heavy chains IGHM, IGHD, IGHA1, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4 can be used as prognostic factors in patients with nasopharyngeal carcinoma and have good prognostic value.
在判定高风险时，可采用以下标准：IGHM的表达量低于182.125时判定为高风险，高于182.125时判定为低风险；IGHD的表达量低于2.985时判定为高风险，高于2.985判定为低风险；IGHA1的表达量低于756.34时判定为高风险，高于756.34时判定为低风险；IGHA2的表达量低于560.23时判定为高风险，高于560.23时判定为低风险；IGHG1的表达量低于9570.435时判定为高风险，高于9570.435时判定为低风险；IGHG2的表达量低于560.23时判定为高风险，高于560.23时判定为低风险；IGHG3的表达量低于558.075时判定为高风险，高于558.075时判定为低风险；IGHG4的表达量低于437.92时判定为高风险，高于437.92时判定为低风险。When judging high risk, the following criteria can be used: when the expression level of IGHM is lower than 182.125, it is judged to be high risk, and when it is higher than 182.125, it is judged to be low risk; when the expression level of IGHD is lower than 2.985, it is judged to be high risk, and when it is higher than 2.985, it is judged to be high risk. It is low risk; when the expression level of IGHA1 is lower than 756.34, it is judged as high risk, and when it is higher than 756.34, it is judged as low risk; when the expression level of IGHA2 is lower than 560.23, it is judged as high risk, and when it is higher than 560.23, it is judged as low risk; When the expression level is lower than 9570.435, it is judged as high risk, when it is higher than 9570.435, it is judged as low risk; when the expression amount of IGHG2 is lower than 560.23, it is judged as high risk, when it is higher than 560.23, it is judged as low risk; when the expression amount of IGHG3 is lower than 558.075, it is judged as high risk. It is judged as high risk, and when it is higher than 558.075, it is judged as low risk; when the expression level of IGHG4 is lower than 437.92, it is judged as high risk, and when it is higher than 437.92, it is judged as low risk.
也可以采用其他已知的方法来确定具体的风险阀值。Other known methods may also be used to determine the specific risk threshold.
以上实施例仅是范例性的，并不对本发明的范围构成任何限制。本领域技术人员应该理 解的是，在不偏离本发明的精神和范围下可以对本发明技术方案的细节和形式进行修改或替换，但这些修改和替换均落入本发明的保护范围内。The above embodiments are only exemplary and do not limit the scope of the present invention in any way. Those skilled in the art should understand that the details and forms of the technical solution of the present invention can be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and substitutions all fall within the protection scope of the present invention.
Claims (8)
- 一种用于检测鼻咽癌预后的抗体组合，其特征在于，所述抗体组合包括IGHM、IGHD、IGHA1、IGHA2、IGHG1、IGHG2、IGHG3、IGHG4中的至少一种。An antibody combination for detecting the prognosis of nasopharyngeal carcinoma, characterized in that the antibody combination includes at least one of IGHM, IGHD, IGHAl, IGHA2, IGHG1, IGHG2, IGHG3, and IGHG4.
- 权利要求1所述的抗体组合在制备鼻咽癌预后确定试剂中的应用。Use of the antibody combination according to claim 1 in preparing a reagent for determining the prognosis of nasopharyngeal carcinoma.
- 用于定量权利要求1所述的抗体组合的试剂在制备鼻咽癌预后确定试剂中的应用。Application of a reagent for quantifying the antibody combination according to claim 1 in preparing a reagent for determining the prognosis of nasopharyngeal carcinoma.
- 根据权利要求3所述的应用，其特征在于，用于定量所述抗体组合的试剂为定量抗体重链mRNA或蛋白的试剂。The application according to claim 3, wherein the reagent for quantifying the antibody combination is a reagent for quantifying antibody heavy chain mRNA or protein.
- 一种用于预测鼻咽癌预后的***，其包括：A system for predicting the prognosis of nasopharyngeal carcinoma, which includes:抗体重链定量装置，其用于确定权利要求1所述的抗体组合的重链的表达量；Antibody heavy chain quantification device, which is used to determine the expression amount of the heavy chain of the antibody combination according to claim 1;数据分析装置，其基于所述抗体重链的表达量，计算确定鼻咽癌的预后；A data analysis device that calculates and determines the prognosis of nasopharyngeal cancer based on the expression amount of the antibody heavy chain;结果输出装置，其用于输出计算的预后结果。A result output device is used to output the calculated prognostic result.
- 根据权利要求5所述的***，其特征在于，所述抗体重链定量装置包括定量检测标志物mRNA或蛋白表达量的试剂、芯片、检测装置、试剂盒。The system according to claim 5, wherein the antibody heavy chain quantitative device includes reagents, chips, detection devices, and kits for quantitatively detecting marker mRNA or protein expression levels.
- 根据权利要求6所述的***，其特征在于，通过定量所述抗体重链的基因mRNA或蛋白表达量得到所述抗体重链的表达量。The system according to claim 6, wherein the expression level of the antibody heavy chain is obtained by quantifying the gene mRNA or protein expression level of the antibody heavy chain.
- 根据权利要求6所述的***，其特征在于，所述IGHM的表达量低于182.125时判定为高风险，高于182.125时判定为低风险；所述IGHD的表达量低于2.985时判定为高风险，高于2.985判定为低风险；所述IGHA1的表达量低于756.34时判定为高风险，高于756.34时判定为低风险；所述IGHA2的表达量低于560.23时判定为高风险，高于560.23时判定为低风险；所述IGHG1的表达量低于9570.435时判定为高风险，高于9570.435时判定为低风险；所述IGHG2的表达量低于560.23时判定为高风险，高于560.23时判定为低风险；所述IGHG3的表达量低于558.075时判定为高风险，高于558.075时判定为低风险；所述IGHG4的表达量低于437.92时判定为高风险，高于437.92时判定为低风险。The system according to claim 6 is characterized in that when the expression level of IGHM is lower than 182.125, it is determined as high risk, and when it is higher than 182.125, it is determined as low risk; when the expression level of IGHD is lower than 2.985, it is determined as high risk, and when it is higher than 2.985, it is determined as low risk; when the expression level of IGHA1 is lower than 756.34, it is determined as high risk, and when it is higher than 756.34, it is determined as low risk; when the expression level of IGHA2 is lower than 560.23, it is determined as high risk, and when it is higher than 560.23, it is determined as low risk. when the expression level of IGHG1 is lower than 9570.435, it is judged as high risk, and when it is higher than 9570.435, it is judged as low risk; when the expression level of IGHG2 is lower than 560.23, it is judged as high risk, and when it is higher than 560.23, it is judged as low risk; when the expression level of IGHG3 is lower than 558.075, it is judged as high risk, and when it is higher than 558.075, it is judged as low risk; when the expression level of IGHG4 is lower than 437.92, it is judged as high risk, and when it is higher than 437.92, it is judged as low risk.
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| "Master's Thesis", 15 January 2009, CENTRAL SOUTH UNIVERSITY, CN, article ZHOU, YIBO: "Preliminary Screening of Immunoediting Related Genes and Immuno-related Abnormal Chromosome Regions in Nasopharyngeal Carcinoma", pages: 1 - 51, XP009554002 * |
| CAI XIN‐ZHANG, ZENG WEI‐QUN, XIANG YI, LIU YI, ZHANG HONG‐MIN, LI HONG, SHE SHA, YANG MIN, XIA KUN, PENG SHI‐FANG: "iTRAQ‐Based Quantitative Proteomic Analysis of Nasopharyngeal Carcinoma", JOURNAL OF CELLULAR BIOCHEMISTRY, JOHN WILEY & SONS, INC. JOHN WILEY & SONS, INC., HOBOKEN, USA, vol. 116, no. 7, 1 July 2015 (2015-07-01), Hoboken, USA, pages 1431 - 1441, XP093148775, ISSN: 0730-2312, DOI: 10.1002/jcb.25105 * |
| FENG XUESONG, CHOWBAY BALRAM, CHEN WEI NING, CHING CHI BUN: "ITRAQ-Coupled 2-D LC-MS/MS Analysis of Differentially Expressed Serum Proteins in Nasopharyngeal Carcinoma Clinical Samples: Potential in Biomarker Discovery", JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS, vol. 1, no. 2, 11 June 2011 (2011-06-11), pages 177 - 183, XP009553907, ISSN: 2156-7018, DOI: 10.1166/jmihi.2011.1022 * |
| GONG LANQI, KWONG DORA LAI-WAN, DAI WEI, WU PINGAN, LI SHANSHAN, YAN QIAN, ZHANG YU, ZHANG BAIFENG, FANG XIAONA, LIU LI, LUO MIN, : "Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma", NATURE COMMUNICATIONS, NATURE PUBLISHING GROUP, UK, vol. 12, no. 1, 1 January 2021 (2021-01-01), UK, pages 1540, XP093148767, ISSN: 2041-1723, DOI: 10.1038/s41467-021-21795-z * |
| LIU, Y. ET AL.: "Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution", NATURE COMMUNICATIONS, vol. 12, 2 February 2021 (2021-02-02), XP093133781, DOI: 10.1038/s41467-021-21043-4 * |
| XU SHENG-EN, WEI XU;FEI-PENG ZHAO; JIN-LIANG YANG; CHUAN-YU LIANG: "Expression of IgM and its significance in human nasopharyngeal carcinoma tissues", CHINA JOURNAL OF MODERN MEDICINE, ZHONGNAN DAXUE, CN, vol. 27, no. 29, 8 December 2017 (2017-12-08), CN , pages 25 - 31, XP093148773, ISSN: 1005-8982, DOI: 10.3969/j.issn.1005-8982.2017.29.006 * |
| ZHANG, GAIXIA: "Analysis of the Value of Serum Immunoglobulin and Light Chain Testing for Nasopharyngeal Carcinoma", CHINA PRACTICAL MEDICINE, CN, vol. 14, no. 36, 31 December 2019 (2019-12-31), CN , pages 77 - 79, XP009553922, ISSN: 1673-7555, DOI: 10.14163/j.cnki.11-5547/r.2019.36.042 * |
| ZOU,Z.N. ET AL.: "Identification of tumor-infiltrating immune cells and microenvironment-relevant genes in nasopharyngeal carcinoma based on gene expression profiling", LIFE SCIENCES, vol. 263, 20 October 2020 (2020-10-20), XP086389309, DOI: 10.1016/j.lfs.2020.118620 * |
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| CN116183920B (en) | 2023-10-20 |
| CN116183920A (en) | 2023-05-30 |
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