| Colorectal cancer(CRC)is one of the most common malignant tumors in the world.It is estimated that more than 1 million patients are diagnosed with colorectal cancer every year.It is estimated that there will be 147,950 newly diagnosed colorectal cancer patients in the United States in 2020,including 104,610 cases of colon cancer and 43,340 cases of rectal cancer.Therefore,the effective prevention and intervention of the disease is of great clinical significance,and it is also the key to overcome this major public health threat.At present,TNM staging is the main clinicopathological index to judge the prognosis of patients with colorectal cancer,but in practice,the prognosis of patients with the same stage is quite different.Therefore,it is of great practical significance to find more prognostic indicators.In 1997,scientists first isolated human leukemia stem cells from human acute myeloid leukemia.Since then,the theory of cancer stem cells(CSCs)has been proposed and a CSC model was established:the tumor is a graded tissue of which CSCs is on the top and is responsible for the production of intra-tumor heterogeneity.There are three main hypotheses about the origin of CSCs:first,it is caused by mutations in normal stem cells,which is based on the fact that mature cells do not have a limited lifespan to accumulate a variety of necessary carcinogenic mutations.Second,stem cells may develop from progenitor cells,there are much more progenitor cells in adult tissue than stem cells,which is more likely to cause carcinogenic transformation.Third,they may be dedifferentiated by cancer cells.Tumor stem cells can be identified by special functional analysis or different surface markers.One of the most reliable CSC markers is CD 133,which has been found in a variety of cancers,including breast,colon,prostate,liver,pancreatic and lung cancer,as well as squamous cell carcinoma of the head and neck.Therefore,targeted therapy or intervention for CD 133+cancer cells seems to be a direction for CSCs eradication.In order to supplement the existing traditional prognostic indicators of colorectal cancer patients and provide more accurate prognosis prediction,this study constructed a prognostic prediction model of colorectal cancer patients from two angles,and also proved that the high expression of TNFRSF19 is related to the poor prognosis of colorectal cancer patients.First,Potential molecules related to the production of colorectal cancer stem cells and prognosis prediction.Based on the three main hypotheses about the origin of CSCs,we speculate that there may be some genes that are differentially expressed not only between CSCs and offspring cancer cells,but also between CSCs and normal cells.We think that the mutations of these genes may be closely related to the production of tumor stem cells.In order to further explore,we downloaded the sequencing chip of differentially expressed genes between Caco2 cell lines CD 133+and CD 133-cells from GEO database,and obtained the gene expression data and related clinical information of 530 patients with colorectal cancer from the Cancer Genome Atlas(TCGA).Finally,we found the gene set that represents our target genes to some extent,and constructed a prognostic prediction model.Second,batch screening of survival-related genes and construction of a 9-gene prognosis prediction signature for CRC patients.In order to improve the accuracy of predicting the prognosis of patients with colorectal cancer,we came up with the idea of directly screening out the genes related to the prognosis of colorectal cancer and constructing a prognosis prediction model.Finally,we successfully constructed a model composed of nine genes,which has high predictive efficiency and can well supplement the existing TNM staging to improve the prediction accuracy.Third,the high expression of TNFRSF19 is associated with metastasis and poor prognosis in patients with colorectal cancer.As a member of the tumor necrosis factor receptor superfamily,we proved that the high expression of TNFRSF19 was significantly associated with lymph node metastasis,distant metastasis and poor survival prognosis in patients with colorectal cancer by Logistic regression and univariate and multivariate Cox regression.Bioinformatics analysis of single gene GSEA was used to explore the potential functional mechanism and pathway. |
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