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Background <p>Despite reducing lung cancer mortality, low-dose computed tomography (LDCT) is limited by a high false positive rate. This study integrates serum miR-4638-3p with LDCT to assess its diagnostic value in non-small cell lung cancer (NSCLC), explore miR-4638-3p’s mechanisms, and analyze the rs6601178 polymorphism’s association with NSCLC susceptibility.</p> Methods <p>Participants comprised 152 healthy controls (HC), 152 patients with benign lung disease (BLD), and 152 NSCLC patients. Serum miR-4638-3p and PTEN levels were measured by RT-qPCR; LDCT scans were performed and interpreted according to established clinical protocols; rs6601178 genotyping was performed using PCR-RFLP. Statistical analyses included logistic regression, ROC analysis, and AUC comparisons. Cell function was detected using CCK-8 and Transwell methods, and the mechanism was explored using PPI analysis and dual-luciferase reporter experiments.</p> Results <p>miR-4638-3p expression was significantly elevated in NSCLC compared to BLD and HC groups and emerged as a robust independent predictor for distinguishing BLD from NSCLC. LDCT alone demonstrated moderate diagnostic performance, while miR-4638-3p alone exhibited higher accuracy. Combining both modalities significantly enhanced diagnostic efficacy. The rs6601178 A allele frequency was reduced in NSCLC relative to HC. The AA genotype was associated with decreased risks of poor tumor differentiation, lymph node metastasis, and advanced-stage disease (III/IV). Knockdown of miR-4638-3p inhibited the proliferation, migration and invasion of NSCLC and validated PTEN as its direct target gene.</p> Conclusion <p>Serum miR-4638-3p serves as a potent diagnostic biomarker for NSCLC. Its integration with LDCT significantly improves diagnostic accuracy, potentially decreasing unnecessary invasive interventions. The rs6601178 A allele confers protection against both NSCLC development and progression. Mechanistically, knockdown of miR-4638-3p inhibits tumour cell biological functions and may act by targeting PTEN.</p>

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LDCT combined with serum miR-4638-3p expression enhances NSCLC diagnostic efficacy and rs6601178 polymorphism susceptibility association

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Zeyu Meng,
  • Ting Xue,
  • Bo Jiang

摘要

Background

Despite reducing lung cancer mortality, low-dose computed tomography (LDCT) is limited by a high false positive rate. This study integrates serum miR-4638-3p with LDCT to assess its diagnostic value in non-small cell lung cancer (NSCLC), explore miR-4638-3p’s mechanisms, and analyze the rs6601178 polymorphism’s association with NSCLC susceptibility.

Methods

Participants comprised 152 healthy controls (HC), 152 patients with benign lung disease (BLD), and 152 NSCLC patients. Serum miR-4638-3p and PTEN levels were measured by RT-qPCR; LDCT scans were performed and interpreted according to established clinical protocols; rs6601178 genotyping was performed using PCR-RFLP. Statistical analyses included logistic regression, ROC analysis, and AUC comparisons. Cell function was detected using CCK-8 and Transwell methods, and the mechanism was explored using PPI analysis and dual-luciferase reporter experiments.

Results

miR-4638-3p expression was significantly elevated in NSCLC compared to BLD and HC groups and emerged as a robust independent predictor for distinguishing BLD from NSCLC. LDCT alone demonstrated moderate diagnostic performance, while miR-4638-3p alone exhibited higher accuracy. Combining both modalities significantly enhanced diagnostic efficacy. The rs6601178 A allele frequency was reduced in NSCLC relative to HC. The AA genotype was associated with decreased risks of poor tumor differentiation, lymph node metastasis, and advanced-stage disease (III/IV). Knockdown of miR-4638-3p inhibited the proliferation, migration and invasion of NSCLC and validated PTEN as its direct target gene.

Conclusion

Serum miR-4638-3p serves as a potent diagnostic biomarker for NSCLC. Its integration with LDCT significantly improves diagnostic accuracy, potentially decreasing unnecessary invasive interventions. The rs6601178 A allele confers protection against both NSCLC development and progression. Mechanistically, knockdown of miR-4638-3p inhibits tumour cell biological functions and may act by targeting PTEN.