Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer

Abstract

Protein PDZ and LIM domain 3 (PDLIM3) is a cytoskeletal protein, colocalizing with α-actinin on the Z line of mature muscle fibers. It plays a key role in dilated cardiomyopathy (DCM), muscular dystrophy, and tumor progression. However, correlations between PDLIM3 expression, prognosis, and tumor-infiltrating immune cells in gastric cancer are unknown. Therefore, we leveraged the Oncomine, GEPIA, GEO, and HPA databases to evaluate PDLIM3 expression in tumors. We also quantified PDLIM3 expression in 15 matched pairs of gastric tumor and nontumor tissues by immunohistochemistry. The Kaplan-Meier method was employed to determine the relationship between PDLIM3 expression and clinical outcomes. GO and KEGG analyses were performed to illuminate the molecular mechanisms of action of PDLIM3. TIMER2.0 and GEPIA were applied to investigate correlations between PDLIM3 expression and gene marker subsets signifying immune infiltration, with TIMER2.0 exploring the correlations between PDLIM3 and related signaling pathways. Gastric cancer tissues were found to express more PDLIM3 than nontumor tissues. PDLIM3 overexpression was associated with shorter OS and PFS of gastric cancer patients (OS HR = 2.02 , P = 9.8 e − 10 ; PFS HR = 1.77 , P = 7.5 e − 06 ). PDLIM3 was also positively correlated with worse OS and PFS according to gastric cancer staging, Her-2 overexpression, differentiation grade, and Lauren classification. PDLIM3 was shown to be associated with immunological responses by GO, while it was related to PI3K/Akt signal pathways by KEGG analysis. Furthermore, increased PDLIM3 expression was significantly correlated with greater infiltration of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. PDLIM3 expression had significant positive correlations with a variety of immune marker subsets. Finally, correlations were found between PDLIM3 and crucial markers of signaling pathways involving PI3K/Akt and p38 MAPK. Thus, upregulation of PDLIM3 was significantly associated with poor prognosis, immune cell infiltration, and activation of two key signal pathways in gastric cancer. We propose that PDLIM3 could be used as a biomarker to predict prognosis and immune cell infiltration in gastric cancer.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration

“…As a consequence, a majority of patients receive their diagnosis when the disease has already advanced to the intermediate or advanced stages (Machlowska et al, 2020). There are multiple treatment alternatives, yet the outcomes continue to be dissatisfactory due to a substantial morbidity and mortality rate (Hu et al, 2022). In recent years, the application of bioinformatics has laid the foundation for the search of effective molecular markers and promoted the research progress of targeted tumor therapy.…”

Multiple bioinformatics analysis identifies IGFBP1 as associated with the prognosis of stomach adenocarcinoma

“…For instance, Zeng et al [ 9 ] research showed that LCP1 was a prognostic biomarker correlated with immune infiltrate in gastric cancer. Hu et al [ 10 ] study indicated that upregulation of PDLIM3 was significantly associated with poor prognosis in STAD. There are relatively few genetic markers based on recurrence-related.…”