Abstract:

Objective To explore the changes in serum levels of miR-499 and miR-362 in patients with advanced non-small cell lung cancer （NSCLC） and their relationship with prognosis. Methods A total of 103 patients with advanced NSCLC at Shanghai University of Medicine & Health Sciences Affiliated Chongming Hospital from January 2020 to October 2021 were selected as the NSCLC group，and 100 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as the control group. Fluorescent quantitative PCR was used to determine and compare the levels of serum miR-499 and miR-362 in the two groups，and the relationship between the two indexes and different clinical characteristics of NSCLC patients was analyzed. According to the clinical outcome of 2-year follow-up，the patients were divided into survival group and death group，and the levels of serum miR-499 and miR-362 were compared between the two groups. The predictive value of miR-499 and miR-362 levels on the prognosis of advanced NSCLC patients were analyzed using receiver operator characteristic （ROC） curves. Results The serum miR-499 level in the NSCLC group （0.34±0.10） was lower than that in the control group （1.25±0.21），while the miR-362 level （1.13±0.27） was higher than that in the control group （0.63±0.15） （t=18.26，P<0.001；t=16.32，P<0.001）. There were statistically significant differences in serum miR-499 and miR-362 levels among patients with different degrees of differentiation （t=11.12，P<0.001； t=16.35，P<0.001），TNM staging （t=13.64，P=0.002； t=8.73，P=0.010） and lymph node metastasis （t=10.02，P=0.003； t=9.65，P=0.004）. The serum miR-499 level in the death group （n=77） （0.24±0.06） was lower than that in the survival group （n=26） （0.35±0.09），while the miR-362 level （1.54±0.32） was higher than that in the survival group （1.08±0.21），with statistically significant differences （t=8.06，P=0.006； t=8.67，P=0.005）. ROC curve analysis showed that the sensitivity of miR-499 and miR-362 in predicting the prognosis of advanced NSCLC patients was 73.46% and 75.85%，respectively，with specificity of 64.42% and 65.61%，AUC of 0.739 （95%CI：0.662-0.805） and 0.743 （95%CI：0.640-0.793）； the sensitivity，specificity，and AUC of serum miR-499 combined with miR-362 in predicting the prognosis of advanced NSCLC patients were 87.63%，85.34%，and 0.875 （95%CI：0.698-0.897），respectively； the combined prediction of miR-499 and miR-362 for AUC area was higher than the individual prediction （Z=4.83，P=0.013； Z=5.17，P=0.009）. Conclusion Advanced NSCLC patients show significant abnormal serum level of miR-499 and miR-362，and as the severity of the disease progressed，the serum level of miR-499 is downregulated more significantly and miR-362 is upregulated more significantly. The combined detection of miR-499 and miR-362 levels has certain predictive value for the prognosis of advanced NSCLC patients.

Key words: Carcinoma, non-small-cell lung, miR-499, miR-362, Prognosis