CXCL8 and CXCL12 genetic variants and serum protein levels in male patients with laryngeal squamous cell carcinoma

Abstract Laryngeal squamous cell carcinoma (LSCC) is a common respiratory malignancy with increasing incidence and a strong association with lifestyle and environmental risk factors. Currently, there are no reliable biomarkers for early detection or prognosis of LSCC. CXCL8 is a proinflammatory chemokine that promotes angiogenesis, tumor growth, and migration, and its genetic variants have been linked to increased cancer risk and poor outcomes. CXCL12 plays a critical role in tumor cell migration, invasion, metastasis, and angiogenesis through the CXCL12/CXCR4 signaling axis. This study aims to investigate the role of CXCL8 and CXCL12 genetic variants, as well as their protein levels, in male patients with LSCC. In all, 300 healthy male controls and 256 male LSCC patients took part in the study. The salting-out technique was used to extract deoxyribonucleic acid (DNA). For genotyping ( CXCL12 rs1029153, rs1801157, rs2297630, and CXCL8 rs2227306), real-time polymerase chain reaction was used. Serum levels were measured by the ELISA method. IBM SPSS Statistics 30.0.0.0 was used to perform statistical analysis. CXCL8 serum levels were significantly higher in LSCC males than in controls (median (IQR): 14.47 (4.89) vs. 12.71 (4.20) pg/ml, p = 0.014). ROC curve analysis demonstrated a modest discriminative ability for CXCL8 (AUC = 0.660, 95% CI: 0.540–0.780, p = 0.009). At the optimal cut-off value of 12.170 pg/ml, selected to maximize sensitivity for screening purposes, serum CXCL8 yielded a sensitivity of 85.0% and a specificity of 42.5%. Although initial unadjusted analyses indicated nominal associations between CXCL12 rs1029153 and rs2297630 variants and advanced LSCC characteristics, none retained significance after Bonferroni adjustment, highlighting their purely exploratory nature. Serum CXCL8 levels were modestly higher in LSCC patients; however, given its limited discrimination (AUC = 0.660) and the absence of validation, serum CXCL8 does not possess clinical utility as a standalone screening or diagnostic biomarker for male LSCC but represents an exploratory finding reflecting tumor-associated inflammation. These findings warrant further investigation into larger independent cohorts and functional studies to determine their biological and clinical relevance.