High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

Songzhe Piao; Lan Zheng; Haihong Zheng; Mengya Zhou; Qin Feng; Suna Zhou; Mang Ke; Haihua Yang; Xuequan Wang

doi:10.1155/2022/2922832

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

J Immunol Res. 2022 Jun 6:2022:2922832. doi: 10.1155/2022/2922832. eCollection 2022.

Authors

Songzhe Piao^{1

2}, Lan Zheng³, Haihong Zheng⁴, Mengya Zhou⁴, Qin Feng¹, Suna Zhou⁵, Mang Ke¹, Haihua Yang⁶, Xuequan Wang⁶

Affiliations

¹ Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Linhai, China.
² Department of Urology, Yanbian University Hospital, Yanji, China.
³ Department of Obstetrics and Gynecology, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Linhai, China.
⁴ Department of Pathology, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Taizhou, China.
⁵ Department of Radiotherapy, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, China.
⁶ Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Radiation Oncology Institute of Enze Medical Health Academy, Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical University, Taizhou, China.

Abstract

Purpose: To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD).

Methods: The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis.

Results: The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD (P < 0.05). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI (P < 0.05) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman's test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression.

Conclusion: Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients.

MeSH terms

Epithelial-Mesenchymal Transition* / genetics
Humans
LIM Domain Proteins* / genetics
Male
Microfilament Proteins* / genetics
Prognosis
Prostatic Neoplasms* / genetics
Prostatic Neoplasms* / pathology
RNA, Messenger / genetics
Tumor Microenvironment / genetics

Substances

LIM Domain Proteins
Microfilament Proteins
PDLIM2 protein, human
RNA, Messenger