Exploring potential therapeutic targets for colorectal tumors based on whole genome sequencing of colorectal tumors and paracancerous tissues.

Objective: Colorectal cancer (CRC) is the third most common tumor worldwide and the second leading cause of cancer-related deaths. Colorectal cancer progresses slowly, and patients have to endure pain for a long time, both before and after surgery. The incidence rate has been increasing year by year in recent years, and the survival rate of patients is low. The number of new cases and deaths is expected to grow to 3.2 million and 1.6 million, respectively, by 2040. Currently, limited treatment (including surgical resection and radiotherapy) and systemic treatment (including chemotherapy and immune-targeted therapy) are the mainstays of colorectal cancer treatment, but the delay in treatment is still caused by untimely detection. In addition, some colorectal cancers are due to diet and lifestyle habits, but some are still due to heredity. Therefore, it is of great importance to analyze the genomic profiles of colorectal cancer and its paraneoplastic tissues, explore the disease-causing risk genes, and search for the potential novel therapeutic targets to improve the therapeutic efficacy of colorectal cancer. Methods: Tumor and adjacent tissue samples were harvested from 26 colorectal cancer patients and divided into tumor and paraneoplastic tissues. Whole genome sequencing was performed on these two groups of samples to obtain somatic and germ line mutation data of the two groups of samples, and then based on the data of the two groups, we screened and analyzed the mutation spectra and mutation characteristics, high-frequency copy number variations, and high-frequency mutated genes of tumor and paraneoplastic samples, thus mapping the genomic map of tumor and cancer susceptibility genes of paraneoplastic samples. The genomic profiles of the tumor and paraneoplastic samples were subsequently mapped. Finally, we performed pan-cancer expression analysis of Results: Significant gene mutation differences were observed between the tumor and adjacent normal tissue by whole genome sequencing. Gene spectral analysis of the tumors revealed that the tumors were characterized by C>T mutation types, and most of the samples were dominated by signature A mutation characteristics. High-frequency copy number analysis showed that most samples had increased copy numbers of gene fragments on chromosomes 7, 13, and 20. In addition, one high-frequency mutated gene (ATAD3B) and six candidate susceptibility genes were screened from the mutation data results, in which the probabilities of susceptibility genes mutated in normal tissues next to cancer were Conclusion: The large differences between single nucleotide mutations and insertion-deletion mutations in somatic cells and germ line cells indicate the large changes in the genome, especially in the non-coding region genome, during the transformation of normal tissue adjacent to cancer into cancerous tissue. In addition, the susceptibility gene