LINC-PINT expression and rs1059698 polymorphism associate with chemoradiotherapy efficacy in Chinese nasopharyngeal carcinoma patients.

BACKGROUND: The identification of predictive biomarkers for nasopharyngeal carcinoma (NPC) treatment response is critical to improving clinical outcomes. Our previous studies demonstrated that the long non-coding RNA (lncRNA) LINC-PINT enhances the radiosensitivity of NPC cells. However, the clinical relevance of functional polymorphisms in LINC-PINT remains unclear. METHODS: A total of 199 Chinese NPC patients who received concurrent platinum-based chemoradiotherapy were enrolled. The association between the LINC-PINT rs1059698 polymorphism and short-term treatment efficacy (assessed 3 months post-treatment) was evaluated using multivariate logistic regression. LINC-PINT expression in NPC tissues was quantified by real-time polymerase chain reaction (PCR). A luciferase reporter assay was performed to assess the effect of rs1059698 on miR-646 binding. Eight machines were further employed learning algorithms to construct predictive models for treatment efficacy. RESULTS: NPC patients with a complete response (CR) showed significantly higher LINC-PINT expression than those with partial response (PR) or progressive disease (PD) (P < 0.05). The rs1059698 CC genotype was significantly associated with an improved treatment response (CR vs. PR + PD, OR = 0.189, 95% CI: 0.042-0.860, P = 0.031). Individuals carrying the CC genotype also exhibited approximately 1.5-fold higher LINC-PINT expression compared to AA genotype carriers (P < 0.001). Functional analysis showed that the A-to-C substitution at rs1059698 disrupted miR-646 binding to LINC-PINT. Additionally, the Gradient Boosting Machine (GBM) model incorporating rs1059698 and clinical variables achieved moderate predictive accuracy (AUC = 0.765 in training and 0.641 in validation). CONCLUSIONS: Our findings suggest that the rs1059698 polymorphism were associated with NPC treatment response possibly by influencing the expression of LINC-PINT or altering miRNA-lncRNA interaction. LINC-PINT rs1059698 may serve as a predictive biomarker for chemoradiotherapy efficacy in NPC.