Local-invasion-based Early Assessment Of Metastatic Risk For Colorectal Cancer

Colorectal cancer is one of the malignant tumors of the digestive tract and the cancer with the highest mortality rate after lung cancer.Most of the deaths of colorectal cancer patients are due to tumor cell metastasis,so the recurrence and metastasis of colorectal cancer are also important and difficult points in the treatment process.According to some previous studies,tumor cells may have metastasized in the early stages of colorectal cancer and usually from the local infiltration of tumor cells into nearby lymphocytes.Therefore,early assessment of the risk of local infiltration can help determine the priority of colorectal cancer treatment options,thereby greatly improving the survival rate of patients.All this shows the urgent need to detect whether colorectal tumors are invasion/metastatic in the early stage.In this study,we recruited a small cohort of 8 colorectal cancer patients,4 of whom had local lymphatic metastasis of colorectal cancer.We collected three tissue samples from these patients:tumor,paracancer and normal tissues,and determined the germline gene mutation profile of the samples through whole exome sequencing.We designed a new statistical parameter,LIP,to calculate and quantitatively describe the contribution of each mutation to the local tumor invasion/metastasis event,by comparing the mutation spectrum between the tumor tissue and the paracancer tissue.Subsequently,we added the sequencing data of tumor samples from 53 colorectal cancer patients to be used for the screening of metastasis driven mutations.And we combined gene expression and survival data of 763 patients with colorectal cancer,which from the colorectal cancer-related big data of the cancer genome atlas database(TCGA)and the genotype tissue expression database(GTEx),to carry out independent verification of each mutation such as functional analysis,expression quantitative trait gene analysis(eQTL)and survival analysis.From this,we identified 10 gene mutations that are closely related to colorectal tumor invasion/metastasis.Further literature analysis shows that five of these genes and their mutations have not been reported to be associated with colorectal cancer in previous studies.Finally,we believe that these 10 gene mutations may be used as biomarkers for the prognosis of colorectal cancer metastasis,and based on these 10 marker mutations,we constructed a logistic regression model for early prediction of the risk of colorectal cancer metastasis.The results of the performance evaluation of the model prove that the model can reliably predict the risk and prognosis of tumor metastasis in patients with colorectal cancer.In conclusion,this study evaluated the metastasis risk of regional lymphatic invasion based on the germline mutation system for the first time,and proposed an early warning mechanism for potential metastasis,which also provided valuable clues for the study of early metastasis mechanisms.