Prognostic and clinicopathological significance of GPRC5A in various cancers: A systematic review and meta-analysis

BACKGROUND: GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A. METHODS: We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I(2) statistics were completed to evaluate the heterogeneity in our study. A random‐effects model was used when significant heterogeneity existed (I(2)>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity. RESULTS: In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20–2.38 I(2) = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02–1.95 I(2) = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33–2.86, I(2) = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15–2.92, I(2) = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis. CONCLUSION: GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.