Investigation and validation of prognostic features associated with transient receptor potential channel genes in gastric cancer
Jinxia Zhao, Huihui Kang, Jiebin Pan, Pengfei SunBackground
An increasing body of evidence suggests an association between transient receptor potential (TRP) channel s and cancer development; however, a systematic evaluation of the combined prognostic value of TRP channel-related genes (TRGs) in gastric cancer (GC) has not been conducted.
Methods
Data were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma, GSE84433, and TRGs. Prognostic genes related to TRP channels and GC were screened, and a risk model was constructed. Functional analysis, immune correlation analysis, and molecular regulatory network construction were performed to identify mechanisms associated with GC prognosis. Finally, the expression of prognostic genes was preliminarily assessed in clinical samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for exploratory validation.
Results
Seven genes associated with GC prognosis (5-hydroxytryptamine 2C receptor ( HTR2C ), MAGEA11 , MAGEA3 , aspartoacylase ( ASPA ), GAD1 , Hedgehog-interacting protein ( HHIP ), and AHNAK ) were identified. A risk model constructed from these genes demonstrated potential prognostic value for patient outcomes. A close association was observed between these genes and the differential abundance of immune cells. The strongest negative correlation was observed between AHNAK and T follicular helper cells. In addition, the prognostic genes were significantly negatively correlated with CD274, which is an immune checkpoint gene. Moreover, complex regulatory relationships among prognostic genes were observed in the regulatory network. Computational analysis predicted regulatory interactions, such as the regulation of AHNAK by EPB41L4A-AS1 and ERICD via hsa-miR-106a-5p. Finally, quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis revealed that the expression pattern of MAGEA11 was consistent with that observed in public databases.
Conclusions
Seven prognostic genes ( HTR2C , MAGEA11 , MAGEA3 , ASPA , GAD1 , HHIP , and AHNAK ) related to TRP channels were identified in GC. These findings provide insight into potential prognostic mechanisms and a basis for further studies on their roles in GC biology.