Abstract
Purpose Liver metastasis remains the leading cause of cancer-related mortality in colorectal cancer. The mechanism of occurrence and development of liver metastasis from colorectal cancer is unclear. Methods The primary tumor tissues and blood samples of 8 patients with liver metastasis of colorectal cancer were collected, followed by nucleic acid extraction and library construction. Whole-exome sequencing was performed to detect the genomic variations. Bioinformatics was used to comprehensively analyze the sequencing data of these samples, including the differences of tumor mutation burden, the characteristics of gene mutations, and signaling pathways. Results The results showed that the top three genes with the highest mutation frequency were TP53, APC, and KRAS. Tumor mutation burden of this study, with a median of 8.34 mutations per MB, was significantly different with The Cancer Genome Atlas databases. Analysis of molecular function and signaling pathways showed that the mutated genes could be classified into five major categories and 39 signaling pathways, involving in Wnt, angiogenesis, P53, Alzheimer disease-presenilin pathway, notch, and cadherin signaling pathway. Conclusions In conclusion, we identified the extensive landscape of altered genes and pathways in colorectal cancer liver metastasis, which will be useful to design clinical therapy for personalized medicine.
Highlights
Colorectal cancer (CRC) is the third most common type of malignancy and leading cause of cancer-related death worldwide [1]
A previous study suggested that the frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in CRC differ among population [6]
We found 1151 single nucleotide variants (SNV) and the prevailing mutations were APC, KRAS, and TP53 (Figure 1, Supplemental Table 2), which is in accordance with data reported by e Cancer Genome Atlas Network [24]
Summary
Colorectal cancer (CRC) is the third most common type of malignancy and leading cause of cancer-related death worldwide [1]. Early detection and prevention or surgical resection of primary and metastatic lesions can reduce the risk of CRC and improve survival of CRC [3,4,5], metastatic CRC is still the leading cause of cancer-related deaths, and treatment options are not as selective. A previous study suggested that the frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in CRC differ among population [6]. AMER1 is a frequently mutated gene in CRC comprising 553 samples [7]. TMEM9, as a novel human transmembrane protein, transactivated by β-catenin functions as a positive feedback regulator of WNT signaling in CRC and mTOR signaling, has been suggested to be an important factor involved in tumorigenesis [8, 9]. erefore, a better understanding of the biological and phenotypic evolution of CRC and its molecular and genetic mechanisms during the transfer process is crucial
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