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

PLoS One. 2021 Mar 31;16(3):e0249040. doi: 10.1371/journal.pone.0249040. eCollection 2021.

Abstract

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 I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>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 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02-1.95 I2 = 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, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15-2.92, I2 = 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Disease-Free Survival
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Prognosis
  • Progression-Free Survival
  • Publication Bias
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • GPRC5A protein, human
  • Receptors, G-Protein-Coupled

Grants and funding

The authors received no specific funding for this work.