Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognost...Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.展开更多
基金The authors extend their appreciation to Taif University,Saudi Arabia,for supporting this work through project No.(TU-DSPP-2024-54).
文摘Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.
文摘目的探讨micro RNA-449a(mi R-449a)在宫颈癌中的表达及其对宫颈癌进展的作用机制。方法采用实时荧光定量聚合酶链反应(q PCR)测定mi R-449a及其靶向调节分子c-Met在宫颈癌组织及正常宫颈标本(对照组)中的表达水平。构建转染mi R-449a高表组(mi R-449a组)、转染c-Met干扰质粒组(si RNA组)和相应的空载质粒组(mock组),q PCR检测mi R-449a和c-Met m RNA表达量;免疫印迹法检测c-Met、MMP2和MMP9蛋白水平变化;细胞划痕修复和Transwell侵袭试验进一步观测mi R-449a和c-Met对细胞迁移和侵袭能力的影响。结果 mi R-449a在宫颈癌组织中表达量低于对照组(P<0.05),c-Met m RNA在宫颈癌组织中的表达高于对照组(P<0.05),两者间呈负相关关系(r=-0.32,P<0.05)。在宫颈癌细胞Hela细胞中过表达mi R-449a后,c-Met m RNA的表达水平降低(P<0.05),并且蛋白水平也明显降低。mi R-449a能显著抑制细胞的迁移和侵袭能力(P<0.05),抑制c-Met表达后也能显著抑制细胞的迁移和侵袭能力(P<0.05)。结论 mi R-449a通过靶向抑制c-Met的表达抑制宫颈癌细胞的迁移和侵袭能力。mi R-449a可能是潜在的宫颈癌筛查和诊断分子标志物,并为宫颈癌个体化治疗提供一个新的方向。
