Prognostic roles of mRNA expression of notch receptors in non-small cell lung cancer

Abstract

Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through “The Kaplan-Meier plotter” (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0.78 (0.69-0.89), p=0.00019, better OS in adenocarcinoma (Ade) patients, HR 0.59 (0.46-0.75), p=1.5e-05, as well as in squamous cell carcinoma (SCC) patients, HR 0.78 (0.62-0.99), p=0.044. mRNA high expression levels of Notch2 and Notch3 were associated with worsen OS for all NSCLC patients, as well as in Ade, but not in SCC patients. mRNA high expression level of Notch4 was not found to be associated with to OS for all NSCLC patients. In addition, mRNA high expression levels of Notch2, Notch3, but Notch4 are significantly associated with the NSCLC patients who have different smoking status. Our results indicate that mRNA expression of Notch receptors may have distinct prognostic values in NSCLC patients. These results will benefit for developing tools to accurately predict the prognosis of NSCLC patients.

The Role of Notch3 in Cancer

“…Clinically in NSCLC, Notch3 overexpression is associated with poorer disease‐free and overall survival, higher TNM stage, and increased LN metastasis rate . Overexpression of Notch3 induces Zinc finger E‐box‐binding (ZEB‐1) activity, decreases E‐cadherin, and upregulates fibronectin, each contributing to EMT and tumor invasiveness.…”

Clinicopathological Significance of S100A14 Expression in Lung Adenocarcinoma

“…Survival Analysis using the KM Plotter Online Database KM Plotter, established using data from the Gene Expression Omnibus database, has been widely used in many studies [24,25].…”

Co-Expression Analysis Reveals Mechanisms Underlying the Varied Roles of NOTCH1 in NSCLC

“…11 The importance of Notch expression is reflected in the fact that NOTCH1 expression levels in nonmutated tumors have opposite prognostic effects in AD and SCC. [17][18][19][20] Although a number of Notch-targeted therapies have been tried (Supplemental Table 1), none has resulted in significant clinical benefit in unselected patient populations. Defining the functional roles of Notch in different tumor subtypes is essential to understand its biology and to provide better therapeutic options for cancer patients.…”