The ferroptosis-related LncRNA CASC9 reveals its potential as a diagnostic and prognostic biomarker in esophageal squamous cell carcinoma.

Abstract

This study aimed to investigate the role of ferroptosis-related long non-coding RNA CASC9 in the carcinogenic process of esophageal squamous cell carcinoma and evaluate its clinical diagnostic and prognostic value. LncRNA microarray screening was performed to identify differentially expressed genes in ESCC tissues. CASC9 expression was validated in 150 paired ESCC tissues, precancerous lesions, and cell lines by qRT-PCR. The correlation between CASC9 expression and clinicopathological characteristics as well as survival outcomes was analyzed. In vitro functional assays were conducted to examine the effects of CASC9 on ESCC cell proliferation, apoptosis, invasion, and migration. The role of CASC9 in ferroptosis was explored by detecting GSH, MDA, and ROS levels. CASC9 was significantly overexpressed in 92.7% of ESCC tissues (mean 11-fold upregulation), showing stepwise elevation during disease progression (normal mucosa→LGIN→HGIN→invasive carcinoma); High CASC9 expression correlated significantly with depth of invasion (P = 0.001) and clinical stage (P = 0.033), serving as an independent risk factor for overall survival (HR = 1.550, P = 0.026); Plasma CASC9 levels were significantly elevated in ESCC patients and markedly decreased at 14 and 30 days postoperatively. CASC9 knockdown markedly suppressed ESCC cell proliferation, invasion, and migration while promoting apoptosis. Reduced GSH and MDA/ROS accumulation indicate that CASC9 regulates ESCC progression via the ferroptosis pathway. In combination with clinicopathological features, a nomogram based on the gene signature presented strong predictive power and risk stratification for ESCC. CASC9 functions as an oncogenic lncRNA that promotes ESCC progression by modulating ferroptosis, representing a promising early diagnostic biomarker, prognostic predictor, and therapeutic target.