In this study, we examined the expression levels of miR-1231 in a large cohort of patients with NSCLC and DM at a single institution between April 2010 and June 2015. In our analysis, results showed that decreased miR-1231 expression was significantly associated with unfavorable clinical parameters. In addition, patients in the miR-1231 high expression group had a better OS compared to the miR-1231 low expression group. Multivariate analysis also showed that miR-1231 was an independent risk factor for favorable OS. In addition, these independent prognostic factors were used to form a nomogram for the estimation of OS. The nomogram showed excellent accuracy in estimating the risk of OS.
The increased incidence of NSCLC is often associated with aging, which explains why NSCLC coincides with other age-related diseases like DM . Many studies have shown that preexisting DM is associated with lower 5-year survival rates in cancer patients [17,18,19]. Several studies have demonstrated that diabetes is associated with poor OS in lung cancer patients [20,21,22]. A study investigated by Ali et al. showed that diabetes at the time of diagnosis was negatively associated with the prognostic importance of OS in NSCLC patients. However, it was rarely considered in clinical studies, partly due to the lack of validated markers. Therefore, we attempted to circumvent this limitation by searching for a microRNA for predicting the prognosis of NSCLC patients with DM.
Cancer development involves several different processes, including many vital genes/proteins. Cancer signatures represent the characteristics that a cell needs to achieve to become and maintain itself as a cancer cell . These signatures guide the cellular pathways associated with cancer initiation and development. Using the expression of miRNAs to predict the clinical prognosis of cancer is more advantageous than mRNAs because miRNAs are considered to be critical post-transcriptional regulators of gene expression [24, 25]. In contrast to mRNAs, these post-transcriptional regulators are highly conserved among species .
Previous studies have shown that miRNAs are associated with the occurrence and development of various cancers, and many miRNAs can serve as valuable biomarkers for cancer diagnosis and prognosis [8, 27]. Recently, many miRNAs have been identified as prognostic biomarkers for NSCLC . miR-1298 was found by Du et al. to be aberrantly expressed in NSCLC, and aberrant miR-1298 can be used as a prognostic biomarker for NSCLS patients . As a novel biomarker, miR-1231 has been considered as a promising prognostic factor for cancer. miR-1231 is a prognostic biomarker and therapeutic target in prostate cancer by Wang et al. . However, no studies are examining the role of miR-1231 as a biomarker in NSCLS. To our knowledge, the present analysis is the first-ever attempt to comprehensively explore prognostic biomarkers based on miR-1231 expression in NSCLC and DM patients. In the present study, we initially tested the expression levels of miR-1231 in NSCLC and DM patients. In addition, we revealed, for the first time, the association between altered miR-1231 expression and existing clinicopathological variables. The results showed that miR-1231 was significantly associated with serum CEA levels, NSCLC stage, surgery, targeted therapy, TKI application, and KPS score. Univariate analysis showed that high expression of miR-1231 was a strong protective predictor of mortality; Kaplan–Meier curves showed that serum CEA level, NSCLC stage, surgery, targeted therapy, TKI application, and KPS score were associated with this. Patients with high miR-1231 levels or who underwent surgery had a lower cumulative incidence of death than those who underwent surgery, respectively. In addition, sex, serum CRP level, albumin level, neutrophil count, PNI score, NSCLC stage, application of platinum, NLR, metastasis, surgery, heart failure, KPS score, and miR-1231 levels were associated with overall mortality. Multivariate analysis showed that miR-1231, surgery, platinum application, albumin level, KPS score, and heart failure as independent prognostic factors predicted OS.
Nomograms help in the visualization of statistical models, calculating predictive values, and graphical assessment of the importance of variables . They have been widely used to predict cancer risk and treatment outcomes. Recently, several studies have successfully created a prognostic nomogram that integrates miRNAs and clinically relevant cancer variables. However, few studies have used the combination of miR-1231 and clinical risk factors to create a prognostic model for NSCLC patients with DM. This study establishes a nomogram model capable of predicting individual prognosis in NSCLC patients with DM based on the combination of miR-1231 and independent clinicopathological characteristics. Nomogram showed good accuracy in estimating the risk of OS. The calibration curves of the risk estimates showed good agreement between observation and prediction. Thus, this is the first prognostic nomogram for patients with NSCLC and DM that considers clinical variables in addition to miR-1231. Based on this model, potentially high-risk patients can be selected for a specific treatment strategy.
There are some limitations to this study. First, experimental studies explaining the biological significance of miR-1231 are lacking. Therefore, the molecular mechanism of miR-1231 should be further investigated in NSCLC. Second, the prognostic map needs to be further validated by prospective, large-scale multicenter studies before it can be applied to clinical practice.