Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC)

Abstract

Till now, no appropriate biomarkers for high‐risk population screening and prognosis prediction have been identified for patients with oesophageal squamous cell carcinoma (ESCC). In this study, by the combined use of data from the Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA)‐oesophageal carcinoma (ESCA), we aimed to screen dysregulated genes with prognostic value in ESCC and the genetic and epigenetic alterations underlying the dysregulation. About 222 genes that had at least fourfold change in ESCC compared with adjacent normal tissues were identified using the microarray data in GDS3838. Among these genes, only PDLIM2 was associated with nodal invasion and overall survival (OS) at the same time. The high PDLIM2 expression group had significantly longer OS and its expression was independently associated with better OS (HR: 0.64, 95% CI: 0.43‐0.95, P = 0.03), after adjustment for gender and pathologic stages. The expression of its exon 7/8/9/10 had the highest AUC value (0.724) and better prognostic value (HR: 0.43, 95% CI: 0.22‐0.83, P = 0.01) than total PDLIM2 expression. PDLIM2 DNA copy deletion was common in ESCC and was associated with decreased gene expression. The methylation status of two CpG sites (cg23696886 and cg20449614) in the proximal promoter region of PDLIM2 showed a moderate negative correlation with the gene expression in PDLIM2 copy neutral/amplification group. In conclusion, we infer that PDLIM2 expression might be a novel prognostic indicator for ESCC patients. Its exon 7/8/9/10 expression had the best prognostic value. Its down‐regulation might be associated with gene‐level copy deletion and promoter hypermethylation.

Three Survival‐Related Genes of Esophageal Squamous Cell Carcinoma Identified by Weighted Gene Coexpression Network Analysis

“…Recent studies constructed prognostic models for ESCC based on gene expression data, with the aim of improving its early diagnosis and personalized treatment. Song et al integrated the analysis of ESCC microarray data from GDS3838 and TCGA-ESCC and confirmed the prognostic value of PDLIM2 expression, which was independently associated with longer OS in ESCC patients [28]. In the current study, the risk score tends to be larger with lower expression of PDLIM2, and ESCC patients with a high-risk score had significantly poorer OS.…”

Sexual Dimorphism in Cellular and Molecular Features in Human ACTH-Secreting Pituitary Adenomas

“…In addition to sex chromosome-encoded genes, several autosomal genes were up-regulated in adenomas from male patients; of note, PDLIM2, PENK, SOX4, FH, PTMA and TMEM97 are all associated with tumourigenesis [64][65][66][67][68][69], and thus could play a role in the less favourable course of corticotrope adenomas in male patients. Links between these factors and the pituitary are known for PTMA and SOX4, as PTMA nuclear staining has been linked to pituitary tumour size [70], and SOX4 is involved in pituitary development, as shown in both zebrafish [71] and human tissues [72].…”

Six Novel Biomarkers for Diagnosis and Prognosis of Esophageal squamous cell carcinoma: validated by scRNA-seq and qPCR

“…Currently, these two databases are widely used for data mining due to their large sample size and complete clinical information. Many studies have identified various biomarkers for ESCC based on TCGA and GEO databases [3][4][5][6][7][8][9]. For example, Mao et al identified a seven-lncRNA signature to predict overall survival in ESCC, which displayed better prognostic predict ability than tumor-node-metastasis (TNM) stage.…”