Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy

Abstract

Background Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance. Methods Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR. Results Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs. Conclusions Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC.

Construct a prognostic model based on fatty acid metabolism/ferroptosis-related genes and reveal the immune heterogeneity and somatic mutation specificity of rectal adenocarcinoma in different groups

“…For example, CSMD1, SACS, FAT3 and RYR2 mutations were found in the high-risk group, but not in the low-risk group. CSMD1, SACS, FAT3 and RYR2 mutations or expression are associated with the prognosis of cancer patients [41][42][43][44]. In addition, the VAF of the top 10 genes with mutation rates were also signi cantly different between the low-and high-risk groups.…”

High-Throughput Sequencing Reveals That Rotundine Inhibits Colorectal Cancer by Regulating Prognosis-Related Genes

“…The expression of IGF2BP3 in tissue specimens was found to be a biomarker for the diagnosis of colorectal cancer in endoscopic biopsies [ 30 ]. SACS is high heterogeneity of expression in COAD and is a predictor of patient survival prognosis [ 31 ]. Doxorubicin inhibits the synthesis of H1-4 through the inhibition of DNA synthesis to achieve the effect of treating colorectal cancer [ 32 ].…”