Notch signaling molecules as prognostic biomarkers for non‑small cell lung cancer

Jin,Meng‑Meng; Ye,Yuan‑Zi; Qian,Zhen‑Dong; Zhang,Yan‑Bei

doi:10.3892/ol.2015.3662

Notch signaling molecules as prognostic biomarkers for non‑small cell lung cancer

Authors:
- Meng‑Meng Jin
- Yuan‑Zi Ye
- Zhen‑Dong Qian
- Yan‑Bei Zhang
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Affiliations: Department of Respiratory Medicine, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Respiratory Medicine, Colored Metal General Staff Hospital of Tongling, Tongling, Anhui 244000, P.R. China
Published online on: September 2, 2015 https://doi.org/10.3892/ol.2015.3662
Pages: 3252-3260

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Abstract

Notch family proteins have been reported to be associated with the initiation and development of various types of tumors. The present study used a prospective design to investigate the role of Notch proteins as novel biomarkers that are capable of predicting the survival outcome for patients with non‑small cell lung cancer (NSCLC). The protein expression of Notch 1, Notch 3 and their ligands, Jagged 1 and Delta‑like 4, was examined using immunohistochemistry in NSCLC tissues and adjacent non‑cancerous lung tissues from 101 patients who underwent surgical treatment. The expression was also correlated with clinicopathological parameters and overall survival (OS). High Notch 1 protein expression was observed in 55.4% (56/101) of NSCLC samples and high Notch 3 expression was observed in 53.5% (54/101). The nuclear expression of Notch 3 was significantly associated with the lymph node status (P=0.0026) and tumor‑node‑metastasis (TNM) stage (P<0.0001), while the coexpression of Notch 1 plus Notch 3 was associated with lymph node status (P=0.0056), TNM stage (P=0.0001) and the histological grading (P=0.0359). In the survival analyses, the high expression of Notch 1 and Notch 3 exhibited an additive effect toward a poorer OS compared with a subtype with low coexpression for the two proteins (P<0.001), with high nuclear Notch 3 expression in the NSCLC patients maintaining independent prognostic significance for the outcome on multivariate analysis. These data further demonstrate a central role for Notch signaling in NSCLC and the significance of Notch 3 as a prognostic indicator of a poorer survival for patients with resected NSCLC.

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