CN114317747A

CN114317747A - Application of SWI5 in prognosis of colon cancer

Info

Publication number: CN114317747A
Application number: CN202111629418.5A
Authority: CN
Inventors: 戴勇; 张巍; 汤冬娥; 陈玉梅; 徐勇; 蔡晚霞
Original assignee: Shenzhen Peoples Hospital
Current assignee: Shenzhen Peoples Hospital
Priority date: 2021-12-28
Filing date: 2021-12-28
Publication date: 2022-04-12

Abstract

The invention discloses an application of SWI5 in prognosis of colon cancer. In a first aspect of the invention, there is provided the use of a reagent for the quantitative detection of SWI5 in the preparation of a prognostic product for colon cancer. According to the application of the embodiment of the application, at least the following beneficial effects are achieved: the invention screens the genes or the proteins thereof which are differentially expressed in colon cancer and normal tissues by a series of bioinformatics analysis methods, firstly proposes the SWI5 gene or the SWI5 protein as the biomarker for judging the prognosis of the colon cancer, makes up the deficiency of the existing prognosis index of the colon cancer, and has good clinical value.

Description

Application of SWI5 in prognosis of colon cancer

Technical Field

The application relates to the technical field of colon cancer diagnosis, in particular to application of SWI5 in prognosis of colon cancer.

Background

Colon cancer is a common malignant tumor in gastrointestinal tract, mostly caused by polyp, starts from abnormal crypt, gradually develops into polyp, and finally develops into colon cancer. One of the most fatal cancers is early-stage colon cancer, which is mainly treated by surgical resection and adjuvant chemotherapy, but the treatment means of metastatic colon cancer with high mortality rate is still relatively deficient. On the other hand, the prognosis of colon cancer is improved overall, but the prognosis of some patients is not optimistic.

Inflammation, a large characteristic of tumors, is one of the carcinogenic factors. The research result shows that the chronic inflammation complements the tumor, so the clinical attempt is made to explore the relationship with the tumor prognosis through the inflammation index. For example, although the prognosis of colon cancer is analyzed by common inflammatory markers such as C-reactive protein and albumin, the effect is not ideal. Therefore, there is a need to provide a marker that can effectively assess the prognosis of colon cancer.

Disclosure of Invention

The present application is directed to solving at least one of the problems in the prior art. Therefore, the application provides a colon cancer marker with good prognostic value.

In a first aspect of the present application, there is provided the use of a reagent for the quantitative detection of SWI5 in the preparation of a prognostic product for colon cancer.

According to the application of the embodiment of the application, at least the following beneficial effects are achieved:

the application screens genes or proteins thereof differentially expressed in colon cancer, a cancer-adjacent tissue and a normal tissue by a series of bioinformatics analysis methods, and firstly provides the SWI5 gene or the SWI5 protein as a biomarker for prognosis judgment of the colon cancer, so that the defects of the existing colon cancer related indexes are overcome, and the clinical value is good.

Among them, SWI5(SWI5 homologous recombination repair protein) as a component of SWI5-SFR1 complex participates in double strand break repair by homologous recombination and can also serve as a transcription regulator of ESR 1. GO analysis showed that the biological processes in which SWI5 participates include cellular responses to estrogen stimuli, repair of double strand breaks by homologous recombination, and positive control of transcription and DNA templates, with molecular functions including nuclear receptor coactivator activity.

In some embodiments of the present application, the agent quantitatively detects the marker at the gene level or at the protein level. The reagent for quantitatively detecting nucleic acid at the gene level is carried out by methods including, but not limited to, Polymerase Chain Reaction (PCR), isothermal amplification reaction (such as loop-mediated isothermal amplification (LAMP), Recombinase Polymerase Amplification (RPA) and the like), probe hybridization technique, northern blotting and the like. Reagents for quantitative detection of SWI5 protein at the protein level were performed by methods including, but not limited to, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (IRA), immunohistochemical staining, western blot, electrophoresis, liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), and the like.

In some embodiments of the present application, the reagent for quantitatively detecting a marker at the gene level is selected from the group consisting of a primer, a probe, and a gene chip. The primer is a primer capable of specifically amplifying the SWI5 gene, the probe is a probe capable of specifically recognizing the SWI5 gene or a transcript of the gene, and the gene chip is a composite structure formed by an array in which the probes are immobilized on a substrate material (specifically, but not limited to, a polymer such as a nylon membrane, a nitrocellulose membrane, glass, and the like).

In some embodiments of the present application, the reagent for quantitatively detecting a marker at the protein level comprises a specific antibody. The specific antibody is an antibody capable of specifically recognizing the SWI5 protein, and specifically includes but is not limited to at least one of a monoclonal antibody and a polyclonal antibody.

In some embodiments of the present application, the prognostic judgment includes predicting survival of the subject. Wherein survival rate is the probability of survival of the subject at a particular time node. In general, survival can be divided into overall survival, median survival, progression-free survival, and the like. In the examples of the present application, applicants found that SWI5 expression in colon cancer patients correlates well with their survival rates, and thus can predict survival in subjects based on SWI5 expression levels. It is understood that other prognostic indicators besides survival rate, such as survival time, etc., can also be used as a parameter or indicator for prognostic judgment. The survival time is a judgment on how long the subject can survive by combining the comprehensive consideration of the condition of the subject, the physical condition and the like, for example, the annual survival rate, the two-year survival rate, the three-year survival rate, the five-year survival rate, the ten-year survival rate and the like are predictions on the possibility of the subject to live for one year, two years, three years, five years and ten years.

In some embodiments of the present application, the survival rate is at least one of overall survival rate, recurrence-free survival rate, progression-free survival rate. Overall survival (OA) refers to the time from the confirmation of colon cancer until death occurs for any reason. Recurrence-free survival (RFS) refers to the time from initial surgery to the earliest evidence of recurrence. Progression-free survival (PFS) refers to the time from randomization to the first occurrence of disease progression, i.e., tumor growth, metastasis of the primary tumor lesion, discovery of new lesions, etc., or death of any cause.

In the examples of the present application, applicants found that the expression level of SWI5 in a subject has a significant correlation with the overall survival rate of the subject, etc., and thus the survival rate of the subject can be predicted by the expression level of SWI 5. Further, the expression difference of SWI5 showed that its expression was significantly increased in tumor tissues, and in the group with higher expression of SWI5, the overall survival rate of patients was decreased. Therefore, more accurate prediction of prognosis of colon cancer patients can be made according to the expression level of SWI 5. Specifically, a set value of the expression level of SWI5 can be given, which can be determined based on the expression level of SWI5 in a normal sample of a normal human and/or a non-colon cancer patient, for example, by selecting an average value of the expression levels of SWI5 in a normal sample of an appropriate sample number or by setting a reasonable multiple such as 1.1-fold, 1.2-fold, 1.5-fold, 2-fold, etc. based on the average value, and when the expression level of SWI5 in a subject exceeds the set value, it is judged that the prognosis of colon cancer is poor. It will be appreciated that the expression levels of SWI5 in a particular one or more colon cancer patient databases or actual colon cancer diagnostic cases may also be ranked to obtain a corresponding median value, and a reasonable fold, such as 1.1 fold, 1.2 fold, 1.5 fold, 2 fold, etc., may be set as the set value based on the median value or based on the average value, and when the expression level of SWI5 in a subject exceeds the set value, the prognosis for colon cancer is determined to be poor. It is understood that the requirement of the setting value determined based on the average value, or the multiple of the average value, etc. has a good classification meaning, and the known sample can be tested by a common statistical test method based on the classification of the setting value, and when the result has a statistical meaning, the setting value can be used as a judgment standard. Further, the setting value may be set plural according to different prognosis levels to form respective gradients, and when the expression level of SWI5 falls within one of the gradient ranges, it is judged as a case of prognosis.

The present examples provide SWI5 as a marker for colon cancer prognosis because its expression was found to be significantly elevated in tumor tissue of colon cancer in database analysis; meanwhile, Kaplan-Meier Plotter analyzes the expression of mRNA and also finds that the overall survival rate of the patient is reduced along with the increase of the expression of SWI 5; furthermore, multifactorial regression analysis also showed that SWI5 could be a prognostic factor for colon cancer.

Additional aspects and advantages of the present application will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the present application.

Drawings

FIG. 1 shows the results of the differential expression of SWI5 between colon cancer patients and normal persons in example 1 of the present application.

FIG. 2 is a survival curve of colon cancer patients analyzed for different SWI5 expression levels by the Kaplan-Meier Plotter database in example 1 of the present application.

FIG. 3 is a forest plot of the overall survival of colon cancer patients analyzed by the multifactorial cox regression model in example 1 of the present application.

Detailed Description

The conception and the resulting technical effects of the present application will be clearly and completely described below in conjunction with the embodiments to fully understand the objects, features and effects of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, and not all embodiments, and other embodiments obtained by those skilled in the art without inventive efforts based on the embodiments of the present application belong to the protection scope of the present application.

The following detailed description of embodiments of the present application is provided for the purpose of illustration only and is not intended to be construed as a limitation of the application.

In the description of the present application, the meaning of a plurality is one or more, the meaning of a plurality is two or more, and the above, below, exceeding, etc. are understood as excluding the present number, and the above, below, within, etc. are understood as including the present number. If the first and second are described for the purpose of distinguishing technical features, they are not to be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.

In the description of the present application, reference to the description of the terms "one embodiment," "some embodiments," "an illustrative embodiment," "an example," "a specific example," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Example 1

Differential expression data of SWI5 in colon cancer and paracancerous tissues and normal tissues were searched in the TCGA library and analyzed, and the results are shown in fig. 1, which is a comparison of colon cancer patients (T group, N ═ 275) and a control group (N group, N ═ 349), wherein the left side of the figure is colon cancer patients, the right side is control group, and the ordinate is normalized (+0.001) and logarithmized values of Transcripts Per Million (TPM). As can be seen from the figure, SWI5 expression was significantly elevated in colon cancer patients compared to normal or para-cancerous tissues (p < 0.05).

The influence of the expression level of SWI5 on the overall survival rate of patients is further researched by utilizing a Kaplan-Meier Plotter database, a survival curve is drawn by adopting a Kaplan-Meier method, and the logrank test has statistical significance. The TPM of SWI5 of different patients was ranked from high to low, and the median after ranking was used as the boundary, those higher than the median were used as high expression groups, and those lower than (or equal to) the median were used as low expression groups, so that 270 patients with colon cancer were grouped, and the results are shown in fig. 2, where the abscissa of the curve is the number of months, the ordinate is the overall survival rate, the upper curve is the low expression group, and the lower curve is the high expression group. As can be seen from the figure, there is a significant difference in survival time for patients grouped at different expression levels (logrank p ═ 0.019). The higher the expression level of SWI5, the lower the overall survival rate of colon cancer patients.

Differential expression data and other clinical information of SWI5 of colon cancer patients are confirmed from a TCGA database, and the relationship between different variables such as age, sex, stage and SWI5 expression of colon cancer patients and the overall survival rate is analyzed by a multifactor regression model, and as a result, as shown in fig. 3, the forest map of multifactor cox regression analysis of overall survival rate is obtained, wherein pT _ stage refers to grouping of tumors according to the range and size of primary tumors, pN _ stage refers to grouping of tumors according to lymph node metastasis conditions, and pM _ stage refers to grouping of tumors according to distal metastasis conditions. As can be seen from the figure, the expression level of SWI5 was significantly correlated with the overall survival rate of colon cancer patients (p <0.05), and thus could be an independent prognostic factor.

From the above results, it can be seen that SWI5 can be used as an independent prognostic factor for colon cancer patients, and has a good prognostic value.

The present application has been described in detail with reference to the embodiments, but the present application is not limited to the embodiments described above, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present application. Furthermore, the embodiments and features of the embodiments of the present application may be combined with each other without conflict.

Claims

1. Use of a reagent for the quantitative detection of SWI5 in the preparation of a prognostic product for colon cancer.

2. The use of claim 1, wherein the agent quantitatively detects the marker at the gene level or at the protein level.

3. The use according to claim 2, wherein said reagents for quantitative detection of said markers at the gene level are selected from the group consisting of primers, probes and gene chips.

4. The use according to claim 2, wherein said reagent for quantitatively detecting said marker at the protein level comprises a specific antibody.

5. The use of claim 1, wherein the prognosis comprises predicting survival of the subject.

6. The use of claim 5, wherein the survival rate is an overall survival rate.

7. The use according to any one of claims 1 to 6, wherein the prognosis is determined to be poor when the expression level of SWI5 is higher than a set value.