DDR1 in esophageal squamous cell carcinoma: bioinformatics discovery and experimental validation.

Esophageal squamous cell carcinoma accounts for almost 90% of all esophageal cancer cases. Recent progress in understanding tumor biology, early diagnosis, and surgical techniques has contributed to the improvements in incidence and mortality. However, the discovery of novel biomarkers remains essential for further reducing disease burden and improving clinical outcomes. The study focuses on investigating the function of DDR1 and its potential clinical utility as a biomarker in esophageal squamous cell carcinoma (ESCC). Five gene expression datasets were included in the study, and a meta-analysis of differentially expressed genes (DEGs) was conducted. Genes identified by three feature selection algorithms were intersected and used for predictive modeling and experimental validation. Clinical validation included reverse transcription quantitative polymerase chain reaction (RT-qPCR) on 40 paired ESCC tumors and adjacent tissues. TE-7 ESCC cells were transfected with anti-miR-199a-5p or pre-miR-199a-5p and analyzed by RT-qPCR and western blotting. DDR1 was significantly upregulated across datasets [pooled average log fold change (FC) =1.06, pooled P<0.05]. A generalized linear model trained using the gene exhibited good performance in classifying tumor and non-tumor samples across four external validation sets. In 40 paired clinical samples, RT-qPCR revealed significantly higher DDR1 and lower miR-199a-5p levels in tumors compared to non-tumor samples (both P<0.001). Anti-miR-199a-5p produced a significant reduction in miR-199a-5p (P=0.041) and a significant increase in DDR1 (P=0.01). MiR-199a-5p inhibition increased DDR1, STAT3, pSTAT3, mesenchymal markers [N-cadherin (CDH2), vimentin (VIM)], and decreased epithelial marker [E-cadherin (CDH1)]. The opposite pattern was observed following miR-199a-5p overexpression (all P<0.05). DDR1 is a candidate biomarker for ESCC. Modulating miR-199a-5p alters DDR1, STAT3 activation, and epithelial-mesenchymal transition (EMT) marker profiles, making miR-199a-5p/DDR1/STAT3/EMT pathway a potential therapeutic target in ESCC.