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

SIMPLE SUMMARY: Colorectal cancer progression involves multi-gene aberration of several biomarkers via the downstream regulation of the MARK/ERK cascade. GNAS gene mutation early identification is important as a prognosticating biomarker for colorectal cancer screening and diagnosis. The role of GNAS gene codons R201C and R201H in CRC tumourigenesis under the control of the Gpa33-antigen promoter is almost exclusively expressed in colorectal cancer. A total of 30 studies (10,689 patients) were included in this analysis, the male population was the most of the total participants (6068 of 10,689), amounting to (57%). The occurrence of GNAS mutation in CRC was 4.8%; (p < 0.001). Codon R201C (40.7%) and R201H (39.7%) sub-codon mutations were the most identified sub-codon mutations in patients with colorectal cancer respectively. 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 I(2) = 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%: I(2) = 94.00%, (p < 0.001), tumour location (colon): 50.5% (95% CI: 33.2–67.6%: I(2) = 97.93%, (p < 0.001), tumour grade (Well): 57.5% (95% CI: 32.4–79.2%: I(2) = 98.10%, (p < 0.001) and tumour late stage: 67.9% (95% CI: 49.7–84.3%: I(2) = 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.