https://orcid.org/0000-0003-1164-0313
Abstract
Introduction
GPR176, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how GPR176 affects tumor immunity and patient prognosis in gastric cancer (GC).
Methods
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of GPR176 in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between GPR176 and clinical traits. Additionally, the potential correlation between GPR176, immune checkpoint genes, and immune cell infiltration levels was investigated.
Results
As per the research findings, GC tissues had higher levels of GPR176 than normal tissues. Additionally, individuals with high expression of GPR176 had a worse 10-year overall survival (OS), in contrast with those having a low expression of GPR176 (p < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of GPR176 demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of GPR176, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of GPR176 expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment.
Conclusion
By examining GPR176 from various biological perspectives, it was determined that GPR176 can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that GPR176 is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.
Data Sharing Statement
This study analysed used clinical data publicly available in the following online databases: TCGA (https://www.cancer.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), GEPIA (http://gepia2.cancer-pku.cn/), Kaplan-Meier Plotter (Kaplan-Meier plotter [Gastric] (kmplot.com)), TIMER (TIMER2.0 (comp-genomics.org)), TCIA (https://tcia.at/), TIDE (http://tide.dfci.harvard.edu/).
Ethics Approval and Informed Consent
The Ethics Committee of the First Affiliated Hospital of Bengbu Medical College [2022] 372 has examined and granted its approval for the research involving human subjects. The study was conducted in adherence to the Helsinki Declaration, which lays out ethical principles for medical research involving human subjects. Patients/participants gave their consent to be involved in this research through the signing of a consent form. Informed consent was provided by all patients.
Acknowledgments
We express our gratitude to Bullet Edits Limited for their valuable contributions to language editing and proofreading of the manuscript. We also acknowledge the open databases, including TCGA, GEO, GEPIA, TIMER, TCIA and TIDE, for providing the necessary platform and datasets for this research.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.