Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing

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.

Ring finger protein 215 is a potential prognostic biomarker involved in immune infiltration and angiogenesis in colorectal cancer

“…Furthermore, it has been demonstrated that the ubiquitin ligase NEDD4 may be an oncogene in endometrial cancer and may stimulate activation of the IGF-1R/PI3K/Akt signaling pathway (31). Yi et al suggested that the frequently highly mutated genes in CRC liver metastases were mainly enriched in gastric acid secretion, biliary secretion, and melanogenesis (32). Overall, the data of the present study confirmed that RNF215 may be necessary for regulating CRC invasion; nevertheless, more research is required to further elucidate the possible modulatory mechanisms of RNF215 in CRC.…”

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier

“… 1 , 2 There are multiple etiological factors for CRC, including diet, lifestyle, and genetic susceptibility. 3 , 4 , 5 Hypernutrition, for example, in the form of a Western or high-fat diet (HFD) intake, along with a sedentary lifestyle, is associated with obesity and dyslipidemia, which in turn promote CRC tumorigenesis and progression. 6 Aberrant lipid metabolism is a hallmark of CRC, and obesity and hyperlipidemia are risk factors for CRC progression.…”

Genome-wide analysis of Chinese keloid patients identifies novel causative genes

“…Genetic variation is an important factor in the occurrence and development of many diseases. Highthroughput sequencing has been widely used in the study of a variety of complex diseases due to its advantages, such as its short consumption time, high throughput, high accuracy, and ability to screen a large number of genes at 1 time, Human whole exome sequencing is a technique to capture and enrich the DNA in the exon region of the whole human genome, and to find genetic mutations related to protein functional variation through high-throughput sequencing (5)(6)(7). Some characteristic mutated genes, such as BRAF (v-raf murine sarcoma viral oncogene homolog B1) and RAF (rat sarcoma viral oncogene homolog), have been identified in melanoma, and highly effective therapies have been developed to target these mutated genes (8,9).…”