Association of LHX1 with cisplatin responsiveness in head and neck squamous cell carcinoma: The Cancer Genome Atlas analysis and in vitro validation

Cisplatin-based chemotherapy is an established treatment for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance remains a major challenge. Biomarkers predictive of cisplatin response may improve risk stratification and treatment selection. We retrospectively analyzed data from The Cancer Genome Atlas (TCGA)-HNSC dataset to investigate the association between LIM homeobox 1 (LHX1) expression and clinical outcomes, particularly among cisplatin-treated patients. Kaplan-Meier survival analysis and differential expression analyses were conducted based on disease-specific survival (DSS) status. LHX1 mRNA expression in tumor and non-tumor tissues was also assessed using TCGA-derived transcriptomic data. In addition, LHX1 mRNA and protein levels were examined in cisplatin-sensitive oral squamous cell carcinoma (OSCC) cell lines and their matched cisplatin-resistant counterparts. Functional relevance was evaluated by performing siRNA-mediated LHX1 knockdown followed by cisplatin treatment in resistant OSCC cells. LHX1 mRNA expression was significantly higher in HNSCC tumors compared with non-tumor tissues (p < 0.001). High LHX1 expression was associated with poor survival in the overall cohort and in the cisplatin-treated subgroup (log-rank p < 0.05 for both). In the cisplatin-treated subgroup, LHX1 expression was significantly associated with DSS status (p < 0.05, q < 0.05). LHX1 expression was also upregulated in cisplatin-resistant OSCC cells (p < 0.05), and its knockdown enhanced cisplatin sensitivity in resistant OSCC cells (p < 0.05). LHX1 may be associated with adverse outcomes and cisplatin resistance in HNSCC/OSCC, supporting its potential as a treatment-relevant biomarker.