Integrated Analyses Identify CDH2 as a Hub Gene Associated with Cisplatin Resistance and Prognosis in Ovarian Cancer

TL;DR

This study identifies CDH2 as a key gene linked to cisplatin resistance and prognosis in ovarian cancer, offering potential for new treatment strategies.

Contribution

CDH2 is newly identified as a hub gene associated with cisplatin resistance and immune infiltration in ovarian cancer.

Findings

CDH2 is upregulated in cisplatin-resistant ovarian cancer cells and correlates with chemoresistance pathways.

High CDH2 expression is linked to increased infiltration of immune cells like NK cells and macrophages.

FDA-approved drugs were identified as potentially relevant to CDH2-associated drug response.

Abstract

Ovarian cancer (OC), the third most common gynecologic malignancy, is characterized by high mortality largely driven by chemotherapy resistance, leading to recurrence and metastasis. Using transcriptomic data from GSE73935, we constructed a weighted gene co-expression network and identified eight hub genes (IGF1R, CDH2, PDGFRA, CDKN1A, SHC1, SPP1, CAV1 and FGF18) associated with cisplatin resistance, among which CDH2 emerged as the most clinically relevant candidate. CDH2 demonstrated moderate diagnostic potential (AUC = 0.792) and was markedly upregulated in cisplatin-resistant A2780/CP70 cells. Independent validation using clinical single-cell RNA-seq data (GSE211956) confirmed its selective enrichment in resistant tumor cell subpopulations. Gene set enrichment analysis linked elevated CDH2 expression to p53 signaling, DNA replication, nucleotide excision repair, and Toll-like receptor pathways, with qPCR supporting upregulation of key downstream genes in resistant cells. Immune deconvolution further indicated that high CDH2 expression correlated with increased infiltration of NK cells, Tregs, macrophages, and neutrophils, and immunohistochemistry verified CDH2 overexpression in cisplatin-resistant tissues. In addition, virtual screening and drug sensitivity profiling identified several FDA-approved agents with potential relevance to CDH2-associated drug response. These findings indicate that CDH2 may serve as a candidate marker associated with cisplatin response in OC, and its association with immune cell infiltration provides further insight into mechanisms potentially underlying chemoresistance.

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