A GNAS Gene Mutation’s Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

Globally, colorectal carcinoma CRC is the third most common cancer and the third most common reason for cancer-associated mortality in both genders. The GNAS mutations are significantly linked with poor prognosis and failed treatment outcomes in CRC. A systematic review and meta-analysis of multiple studies executed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria and registered with PROSPERO (registration number: CRD42021256452). The initial search includes a total of 271 publications; however, only 30 studies that merit the eligibility criteria were eventually chosen. Data analysis via OpenMeta Analyst and comprehensive meta-analysis 3.0 (CMA 3.0) software were used to investigate the prevalence of GNAS gene mutation among CRC patients. The meta-analysis consisted of 10,689 participants with most being males 6068/10,689 (56.8%). Overall, prevalence of GNAS mutations was 4.8% (95% CI: 3.1–7.3) with I2 = 94.39% and (p < 0.001). In 11/30 studies, the frequency of GNAS gene mutations was majorly in codons R201C [40.7% (95% CI: 29.2–53.2%)] and in codon R201H [39.7% (95% CI = 27.1–53.8)]. Overall prevalence of GNAS mutations was highest among the male gender: 53.9% (95% CI: 48.2–59.5%: I2 = 94.00%, (p < 0.001), tumour location (colon): 50.5% (95% CI: 33.2–67.6%: I2 = 97.93%, (p < 0.001), tumour grade (Well): 57.5% (95% CI: 32.4–79.2%: I2 = 98.10%, (p < 0.001) and tumour late stage: 67.9% (95% CI: 49.7–84.3%: I2 = 98.%, (p < 0.001). When stratified according to study location, a higher prevalence was observed in Japan (26.8%) while Italy has the lowest (0.4%). Overall prevalence of GNAS gene mutations was 4.8% with codons R201C and R201H being the most mutated, and the results conformed with numerous published studies on GNAS mutation.

Identification of Genomic Signatures for Colorectal Cancer Survival Using Exploratory Data Mining

“…The 32-gene panel included several genes involved in cancer progression and its putative response to treatment [ 25 , 26 ]. Moreover, our enrichment analysis revealed findings consistent with these 32 genes that were pertinent to the changes in copy number associated with colorectal cancer development and progression [ 23 ], gene mutations important as prognostic biomarkers for colorectal cancer screening and diagnosis [ 26 ], and the upregulation of anti-apoptotic proteins that encourage epithelial–mesenchymal cellular transition (EMT, [ 23 , 25 , 26 , 27 ]).…”

DNA methylation landscape reveals GNAS as a decitabine-responsive marker in patients with acute myeloid leukemia

“…GNAS (G-protein α subunit), a PKA activator, has frequently been associated with the development of pancreatic cancer [ 31 , 32 ], small cell lung cancer [33] , and colorectal cancer [34] . It has been shown that GNAS can function as a proto-oncogene in solid tumors [35] , while in Sonic hedgehog-driven medulloblastomas, GNAS served as a tumor suppressor [36] .…”

The salvage lenvatinib-based regimen provides survival benefit in patients with refractory metastatic colorectal cancer

“…According to the NGS analysis (Figure 6), GNAS mutation was the only gene alteration correlat-ed with a worse treatment response. A metaanalysis suggested that GNAS mutations are significantly linked with poor prognosis and treatment failure in CRC patients [22]. Survival analyses revealed that patients with KRAS mutations had significantly longer OS1 (P = 0.017), suggesting that the RAS mutation is a predictive marker for better treatment outcomes in patients receiving lenvatinib-based regimens.…”