Purpose
Semaphorin 5A (
SEMA5A
) and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of
SEMA5A
in autophagy
via
its associated ARGs and the underlying molecular mechanisms remain unresolved.
Patients and Methods
GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with
SEMA5A
to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and
SEMA5A
. The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR).
Results
Ninety candidate genes were identified for Spearman correlation with
SEMA5A
, revealing
TNFSF11, BMP6, ITPR1
, and
DLC1
with correlation coefficients exceeding 0.3. Survival analysis underscored
DLC1
and
BMP6
as key genes due to significant prognostic differences. GSEA implicated
SEMA5A, BMP6
, and
DLC1
in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of
SEMA5A
and
BMP6
with M1 macrophages, while
DLC1
exhibited the strongest association with the immune checkpoint
PDCD1LG2
(p < 0.05, cor = 0.43). The mRNA expression level of
SEMA5A
was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas
DLC1
and
BMP6
mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001).
Conclusion
ARGs
BMP6 and DLC1
, associated with
SEMA5A
, were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.