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RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy.

ABSTRACT: Ring1 and YY1 binding protein (RYBP) is a member of the Polycomb group (PcG) proteins and regulates cell growth through both PcG-dependent and -independent mechanisms. Our initial study indicated that RYBP is down-regulated in human non-small cell lung cancer (NSCLC) tissues. The present study determined the molecular role of RYBP in the development of NSCLC. We systemically investigated the association between the RYBP expression and the survival of patients with NSCLC. We also carried out in vitro and in vivo studies to explore the molecular basis for the tumor suppressor role of RYBP in NSCLC. Our clinical results demonstrated that the RYBP mRNA and protein expressions were significantly down-regulated in NSCLC and significantly linked to the poor prognosis in NSCLC patients. The enforced expression of RYBP inhibited cell survival, induced apoptosis, and increased chemosensitivity in NSCLC cells; knockdown of RYBP showed the opposite effects. Moreover, adenoviral delivery of RYBP sensitized the NSCLC cells to chemotherapy in vivo. In addition, RYBP expression was induced by paclitaxel, the first-line chemotherapeutic agent for NSCLC. Our results reveal that RYBP inhibits the aggressiveness of NSCLC cells and downregulation of RYBP is associated with poor prognosis, suggesting that RYBP could be developed as a biomarker and a novel target for therapy in patients with lung cancer.

SUBMITTER: Voruganti S

PROVIDER: S-EPMC4733564 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy.

Voruganti Sukesh S Xu Fangxiu F Qin Jiang-Jiang JJ Guo Yan Y Sarkar Sushanta S Gao Ming M Zheng Zhijie Z Wang Ming-Hai MH Zhou Jianwei J Qian Biyun B Zhang Ruiwen R Wang Wei W

Cancer letters 20150921 2

Ring1 and YY1 binding protein (RYBP) is a member of the Polycomb group (PcG) proteins and regulates cell growth through both PcG-dependent and -independent mechanisms. Our initial study indicated that RYBP is down-regulated in human non-small cell lung cancer (NSCLC) tissues. The present study determined the molecular role of RYBP in the development of NSCLC. We systemically investigated the association between the RYBP expression and the survival of patients with NSCLC. We also carried out in v ...[more]

PMID: 26404750

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Project description:BackgroundImmunotherapy has emerged as a promising treatment strategy in malignant tumors. Inhibitors and neutralizing antibodies targeted PD-1 or PD-L1 show improved clinical outcomes in advanced non-small cell lung cancers (NSCLCs). Previous studies concluded that PD-1 was mainly expressed on activated T cells, B cells and other immune cells. Recently, two studies suggested that PD-1 could be detected in the tumor cells of melanoma and hepatocellular carcinoma. Tumor-endogenous PD-1 in NSCLCs has not been reported at present. Thus, we intended to explore the expression and prognostic relevance of tumor-endogenous PD-1 in NSCLCs.MethodsWe detected the PD-1 expression in fresh tumor samples and tumor slices by flow cytometer and immunohistochemical analysis respectively. Overall survival (OS) and dis-ease-free survival (DFS) were analyzed with Kaplan-Meier survival curve. We explored the PD-1 expression in lung cancer cell lines and investigated its effect on cell proliferation.ResultsFlow cytometry showed that tumor cells with endogenous PD-1 constituted 2.08%, 2.42%, 1.79%, and 1.21% in 4 clinical NSCLC samples respectively. Thirty-four patients (34%) in the cohort were positive for tumor-endogenous PD-1 in IHC analysis. Patients with tumor-endogenous PD-1 had significantly worse 5-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis identified tumor-endogenous PD-1 as an independent risk factor (HR =3.807, 95% CI: 2.031-7.135, P<0.05). PD-1 could be observed in 4 kinds of lung cancer cell lines (A549, H1975, H1299 and HCC827). PD-1 overexpression could enhance proliferation and clone formation of these cell lines.ConclusionsPD-1 was endogenously expressed on the tumor cells of NSCLCs, and it could serve as an independent prognostic risk factor. The molecular mechanism of inferior survival of tumor-endogenous PD-1 may attribute to its role in promoting cell proliferation and clone formation. Our results demonstrated the non-immune role of PD-1 in tumor microenvironment and may provide new thinking for the therapy of NSCLCs.

Project description:BACKGROUND: Current staging system for small cell lung cancer (SCLC) categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion. METHODS: We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated. RESULTS: 84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30-3.10), age (HR, 1.04; 95% CI, 1.03-1.06), and extensive stage (HR, 1.39; 95% CI, 1.06-1.84) were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25-0.42) was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001). Among SCLC patients of either limited (median 180 vs. 460, p<0.0001) or extensive (median 125 vs. 207, p<0.0001) stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively. CONCLUSION: Endobronchial mucosal involvement is an independent prognostic factor for SCLC patients and associated with decreased survival days.

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RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy.

Publications

RYBP predicts survival of patients with non-small cell lung cancer and regulates tumor cell growth and the response to chemotherapy.

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