Hui Yi1,2, Zhi-Wei Liao2, Jun-Jie Chen1, Xin-Yu Shi1, Guo-Liang Chen1, Guan-Ting Wu1, Di-Yuan Zhou1, Guo-Qiang Zhou3, Jin-Yu Huang4, Lian Lian5, Zheng-Yuan Yu6, Song-Bing He1. 1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. 2. Department of General Surgery, Renhe Hospital, Baoshan District, Shanghai, China. 3. Department of Gastrointestinal Surgery, Changshu No. 2 Hospital, Suzhou, China. 4. Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China. 5. Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, China. 6. Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, China.
Abstract
BACKGROUND: Liver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics. METHODS: This study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data. RESULTS: we found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis. CONCLUSIONS: This study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Liver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics. METHODS: This study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data. RESULTS: we found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis. CONCLUSIONS: This study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
Whole-exome sequencing; colorectal cancer (CRC); liver metastasis
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