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Main bronchus location is a predictor for metastasis and prognosis in lung adenocarcinoma: A large cohort analysis.

ABSTRACT: OBJECTIVES:In the literature, inconsistent associations between the primary locations of lung adenocarcinomas (ADCs) with patient prognosis have been reported, due to varying definitions for central and peripheral locations. In this study, we investigated the clinical characteristics and prognoses of ADCs located in the main bronchus. METHODS:A total of 397,189 lung ADCs registered from 2004 to 2013 in the National Cancer Database (NCDB) were extracted and divided into main bronchus-located ADCs (2.5%, N?=?10,111) and non-main bronchus ADCs (97.5%, N?=?387,078). The ADCs located in the main bronchus and those not in the main bronchus were compared in terms of patient prognosis, lymph node involvement, distant metastases and other clinical features, including rate of curative-intent resection, histologic grade, and stage. RESULTS:ADCs located in the main bronchus had significantly worse patient survival than those in the non-main bronchus, both for all patients (HR?=?1.82, 95% CI 1.78-1.86) and for those undergoing curative-intent resection (HR?=?2.49, 95% CI 2.23-2.78). Furthermore, ADCs located in the main bronchus had a significantly higher rate of lymph node involvement and distant metastasis than those not in the main bronchus, when stratified by tumor size (trend test, p?

SUBMITTER: Yang L

PROVIDER: S-EPMC7678407 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Main bronchus location is a predictor for metastasis and prognosis in lung adenocarcinoma: A large cohort analysis.

Yang Lin L Wang Shidan S Gerber David E DE Zhou Yunyun Y Xu Feng F Liu Jiewei J Liang Hao H Xiao Guanghua G Zhou Qinghua Q Gazdar Adi A Xie Yang Y

Lung cancer (Amsterdam, Netherlands) 20180319

<h4>Objectives</h4>In the literature, inconsistent associations between the primary locations of lung adenocarcinomas (ADCs) with patient prognosis have been reported, due to varying definitions for central and peripheral locations. In this study, we investigated the clinical characteristics and prognoses of ADCs located in the main bronchus.<h4>Methods</h4>A total of 397,189 lung ADCs registered from 2004 to 2013 in the National Cancer Database (NCDB) were extracted and divided into main bronch ...[more]

PMID: 29748011

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Project description:BackgroundDifferent histological subtypes of non-small cell lung cancer (NSCLC) show different molecular characteristics and responses to therapeutic strategy. Identification of specific gene, clarification of its special roles and molecular mechanisms are crucial for developing new therapeutic approach for particular subtype patients.MethodsSurgical specimens of 540 NSCLC patients were recruited. Immunohistochemistry was used to detect SOX30 expression, and correlations with clinical parameters were analyzed. Functional experiments and gene ontology analysis were performed to investigate roles of SOX30. Network analysis, TOP/FOP-Flash assays, luciferase reporter assays and ChIP-PCR assays were performed to determine the mechanism. Survival analyses were calculated by Kaplan-Meier and Cox regression. Recovery experiment was investigated the importance of the target of SOX30.ResultsSOX30 expression is closely associated with histological types of NSCLC, and metastasis of adenocarcinoma (ADC) patients but not of squamous cell carcinoma (SCC) patients. SOX30 strongly inhibits cancer cell migration and invasion in ADC cell lines, whrereas not affects cell migration and invasion in SCC cell lines. The genes associated with SOX30 preferentially enrich in metastasis process and Wnt-signaling in only ADC patients. Consistently, SOX30 is negatively associated with the expression of Wnt-signaling and metastasis-related gene CTNNB1 (?-catenin) in ADC, but not in SCC. At the molecular level, SOX30 represses Wnt-signaling by directly transcriptional inhibition of CTNNB1 in ADC, and also not in SCC. In the clinical, SOX30 is a favorable and independent prognostic factor in ADC patients, whereas is an unfavorable and independent prognostic factor in SCC patients. Moreover, SOX30 expression is a double face early-stage prognostic biomarker in ADC and SCC patients. In addition, forcible restoration of CTNNB1 indeed can inhibit the anti-metastatic role of SOX30 in ADC patients.ConclusionsIn early-stage ADC patients, elevated SOX30 expression inhibits tumor-metastasis by directly binding to CTNNB1 promoter resulting in a favorable prognosis of these patients. However, in early-stage SCC patients, SOX30 has no inhibitory role on tumor-metastasis due to not binding to CTNNB1 promoter leading to an unfavorable prognosis of the patients. This study highlights a special role and prognostic value of SOX30 in ADC, providing a novel therapeutic target for particular subtype NSCLC patients.

Dataset Information

Main bronchus location is a predictor for metastasis and prognosis in lung adenocarcinoma: A large cohort analysis.

Publications

Main bronchus location is a predictor for metastasis and prognosis in lung adenocarcinoma: A large cohort analysis.

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