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Novel prognostic model for stratifying survival in stage I lung adenocarcinoma patients.

ABSTRACT: PURPOSE:We combined conventional clinical and pathological characteristics and pathological architectural grading scores to develop a prognostic model to identify a specific group of patients with stage I lung adenocarcinomas with poor survival following surgery. METHODS:This retrospective study included 198 patients with stage I lung adenocarcinomas recruited from 2004 to 2013. Multivariate analyses were used to confirm independent risk factors, which were checked for internal validity using the bootstrapping method. The prognostic scores, derived from ?-coefficients using the Cox regression model, classified patients into high- and low-risk groups. The predictive performance and discriminative ability of the model were assessed by the area under the receiver operating characteristic curve (AUC), concordance index (C-index) and Kaplan-Meier survival analyses. RESULTS:Three risk factors were identified: T2 (rounding of ?-coefficients?=?81), necrosis (rounding of ?-coefficients?=?67), and pathological architectural score of 5-6 (rounding of ?-coefficients?=?58). The final prognostic score was the sum of points. The derived prognostic scores stratified patients into low- (score???103) and high- (score?>?103) risk groups, with significant differences in 5-year overall survival (high vs. low risk: 49.3% vs. 88.0%, respectively; hazard ratio: 4.55; p?

SUBMITTER: Liu DH

PROVIDER: S-EPMC7040084 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Novel prognostic model for stratifying survival in stage I lung adenocarcinoma patients.

Liu Di-Han DH Ye Zheng-Hao ZH Chen Si S Sun Xue-Song XS Hou Jing-Yu JY Zhao Ze-Rui ZR Long Hao H

Journal of cancer research and clinical oncology 20191228 3

<h4>Purpose</h4>We combined conventional clinical and pathological characteristics and pathological architectural grading scores to develop a prognostic model to identify a specific group of patients with stage I lung adenocarcinomas with poor survival following surgery.<h4>Methods</h4>This retrospective study included 198 patients with stage I lung adenocarcinomas recruited from 2004 to 2013. Multivariate analyses were used to confirm independent risk factors, which were checked for internal va ...[more]

PMID: 31884561

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Project description:The proportion of patients with stage I lung adenocarcinoma (LUAD) has dramatically increased with the prevalence of low-dose computed tomography use for screening. Up to 30% of patients with stage I LUAD experience recurrence within 5 years after curative surgery. A robust risk stratification tool is urgently needed to identify patients who might benefit from adjuvant treatment. In this first investigation of the relationship between metabolic reprogramming and recurrence in stage I LUAD, we developed a recurrence-associated metabolic signature (RAMS). This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognoses of patients with stage I LUAD. The clinical significance and immune landscapes of the signature were comprehensively analyzed. Based on a gene expression profile from the GSE31210 database, functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stage I LUAD with relapse from those without relapse. We then identified a metabolic signature (i.e., RAMS) represented by 2 genes (ACADM and RPS8) significantly related to recurrence-free survival and overall survival times of patients with stage I LUAD using transcriptome data analysis of a training set. The training set was well validated in a test set. The discriminatory power of the 2 gene metabolic signature was further validated using protein values in an additional independent cohort. The results indicated a clear association between a high risk score and a very poor patient prognosis. Stratification analysis and multivariate Cox regression analysis showed that the RAMS was an independent prognostic factor. We also found that the risk score was positively correlated with inflammatory response, the antigen-presenting process, and the expression levels of many immunosuppressive checkpoint molecules (e.g., PD-L1, PD-L2, B7-H3, galectin-9, and FGL-1). These results suggested that high risk patients had immune response suppression. Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high risk patients. However, the patients could respond better to chemotherapy. This study is the first to highlight the relationship between metabolic reprogramming and recurrence in stage I LUAD, and is the first to also develop a clinically feasible signature. This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm.

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Novel prognostic model for stratifying survival in stage I lung adenocarcinoma patients.

Publications

Novel prognostic model for stratifying survival in stage I lung adenocarcinoma patients.

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