LINC00673 upregulation and rs9914618 polymorphism: associations with risk and prognosis of lung squamous cell carcinoma

Abstract

ABSTRACT Background The specific effect of the LINC00673 rs9914618 single nucleotide polymorphism (SNP) on lung squamous cell carcinoma (LUSC) remains unclear. This study aims to evaluate its association with LUSC susceptibility and prognosis. Materials and methods We recruited 305 LUSC patients and 336 healthy controls. LINC00673 expression was measured by qRT-PCR. The rs9914618 genotype was determined using TaqMan assays. Disease-free survival was estimated by Kaplan-Meier analysis. Multivariate Cox regression yielded hazard ratios with 95% confidence intervals. Results LINC00673 expression was significantly upregulated in LUSC tissues and serum relative to the control group. The A allele at rs9914618 was positively associated with increased LINC00673 transcription. Carriers of the A allele or AA genotype had a higher risk of LUSC. Patients with GA or AA genotypes showed more severe clinicopathological features and lower five‑year survival rates. The rs9914618 polymorphism was validated as an independent prognostic factor. Conclusion The LINC00673 rs9914618 polymorphism may serve as a potential prognostic factor for LUSC, showing significant associations with patient outcomes and risk stratification. PLAIN LANGUAGE SUMMARY Lung squamous cell carcinoma (LUSC) is a common type of lung cancer. Currently, diagnosis depends mainly on imaging and biopsy; simple blood tests for assessing disease risk or predicting survival are not available. Each person carries small natural DNA variations called single nucleotide polymorphisms (SNPs). Some SNPs may influence gene activity and, in turn, cancer development or prognosis. This study focused on one SNP (rs9914618) in the LINC00673 gene. Our data indicated that LINC00673 activity was higher in tumor tissues and serum from LUSC patients than in samples from healthy controls. Individuals who carried the A allele of rs9914618 tended to show increased LINC00673 activity. Those with the AA genotype or at least one A allele appeared to have a higher risk of LUSC. Among patients, those with GA or AA genotypes showed more aggressive tumor features and lower five-year survival rates. The rs9914618 variant alone was found to be an independent predictor of patient outcomes, regardless of age or sex. These results suggest that the rs9914618 variant in LINC00673 may serve as a prognostic factor. In the future, it could help identify individuals who might benefit from enhanced screening or more intensive treatment. Of note, this study addressed risk prediction and prognosis; no screening test based on this marker has been approved for asymptomatic people, and further validation will be needed before clinical use.