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

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-in...

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Main Authors: Xinpeng Hu, Minfeng Chen, Qiang Ruan, Changzheng Shi, Jinghua Pan, Liangping Luo
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/2039447
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author Xinpeng Hu
Minfeng Chen
Qiang Ruan
Changzheng Shi
Jinghua Pan
Liangping Luo
author_facet Xinpeng Hu
Minfeng Chen
Qiang Ruan
Changzheng Shi
Jinghua Pan
Liangping Luo
author_sort Xinpeng Hu
collection DOAJ
description 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=9.8e−10; PFS HR=1.77, P=7.5e−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.
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spelling doaj-art-02038e125d264968a9f206b0345893842025-02-03T01:08:46ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/2039447Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric CancerXinpeng Hu0Minfeng Chen1Qiang Ruan2Changzheng Shi3Jinghua Pan4Liangping Luo5Medical Imaging CenterCollege of PharmacyDepartment of The Second Area of Gastrointestinal SurgeryMedical Imaging CenterDepartment of General SurgeryMedical Imaging CenterProtein 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=9.8e−10; PFS HR=1.77, P=7.5e−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.http://dx.doi.org/10.1155/2022/2039447
spellingShingle Xinpeng Hu
Minfeng Chen
Qiang Ruan
Changzheng Shi
Jinghua Pan
Liangping Luo
Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
Journal of Immunology Research
title Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
title_full Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
title_fullStr Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
title_full_unstemmed Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
title_short Comprehensive Analysis of PDLIM3 Expression Profile, Prognostic Value, and Correlations with Immune Infiltrates in Gastric Cancer
title_sort comprehensive analysis of pdlim3 expression profile prognostic value and correlations with immune infiltrates in gastric cancer
url http://dx.doi.org/10.1155/2022/2039447
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