PCDHGA10 as a potential prognostic biomarker and correlated with immune infiltration in gastric cancer

Abstract

Background: Gastric cancer (GC) is one of the most common malignant tumors and is associated with poor prognosis. To improve the prognosis of GC patients, an effective immune-related prognostic biomarker is urgent. Here, we aim to explore the correlation between the expression of procalcitonin gamma subfamily A, 10 (PCDHGA10) and clinicopathological characteristics, especially its relation with tumor-infiltrating immune cells (TILs) in GC.

Methods: The differential mRNA expression of PCDHGA10 between GC tissues and normal gastric mucosa and prognostic potential were assessed from The Cancer Genome Atlas (TCGA). Then, based on tissue microarrays (TMAs) with multiplex immunohistochemistry (mIHC) from GC patients, we statistically assess the correlation between PCDHGA10 protein expression and the clinical profiles and prognosis of the patients. Additionally, with IHC and mIHC, we applied the machine-learning algorithms to evaluate the localization and expression levels of TILs and immune checkpoints in the tumor microenvironment. We analyzed the relationship between PCDHGA10 protein expression and TILs and immune checkpoints.

Results: Through the database and TMA analysis, the expression of PCDHGA10 was significantly higher in GC tissues compared with normal tissues. High PCDHGA10 expression independently predicted poor prognosis in GC. Additionally, elevated PCDHGA10 expression was positively associated with the number of CD8⁺ T cells, CD68⁺ macrophages, Foxp3⁺ T cells, and CD4⁺ T cells in GC tissues and the stromal region. Besides, the expression of PCDHGA10 was positively correlated with immune checkpoints, including CTLA-4, LAG3, and PD-L1.

Conclusions: PCDHGA10 might be a potential prognostic marker and an immunological therapeutic target for GC.

Keywords: PCDHGA10; gastric cancer; immunotherapy; multiplex immunohistochemistry; prognosis; tumor microenvironment.

Figure 1

Bioinformatics analysis of PCDHGA10 mRNA expression in gastric cancer (GC). (A) The mRNA levels of PCDHGA10 in gastric cancer tissues was higher than that in benign gastric tissues. (B) High PCDHGA10 mRNA levels correlated with poor overall survival in GC. (C) The receiver operating characteristic curve for PCDHGA10 mRNA levels in GC. ** p < 0.05.

Figure 2

PCDHGA10 protein expression in gastric cancer. PCDHGA10 protein in gastric cancer (A) and peritumoral tissues (B) with fluorescence multiplex immunohistochemistry. Purplish red: PCDHGA10, green: CK, blue: DAPI. Left column magnification ×40; right two column magnification ×200. DAPI: 4, 6-diamino-2-phenyl indole; CK, cytokeratin.

Figure 3

Prognostic analysis of PCDHGA10 protein expression levels. (A) Overall survival analysis of PCDHGA10 protein levels based on gastric cancer tissue microarray. (B) A forest plot visualizing the univariate and multivariate analysis of PCDHGA10 in gastric cancer.

Figure 4

Relationship between PCDHGA10 protein expression and tumor-infiltrating immune cells and immune checkpoints. (A-C) Multispectral composite of CD3, CD4, CD8, CD11b, CD66b, CD68, CK and DAPI, magnification ×200. (D) Four-color multispectral composite of LAG3, PD1, CK and DAPI, magnification ×200. Green: CK, blue: DAPI. (E) Correlation analysis of PCDHGA10 protein expression and tumor-infiltrating immune cells. (F) Correlation analysis of PCDHGA10 protein expression and immune checkpoints. DAPI: 4, 6-diamino-2-phenyl indole; CK, cytokeratin. * p < 0.05.