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

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.

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.

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).

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.