A novel recurrence-associated metabolic prognostic model for risk stratification and therapeutic response prediction in patients with stage I lung adenocarcinoma

Purpose The high 5-year disease relapse rate in patients with stage I lung adenocarcinoma indicates the need for additional risk stratification parameters. This study assessed whether gene signatures translate into a pathologic feature for better disease stratification. Materials and Methods The mutual interdependence and risk stratification power of three gene signatures, cell cycle, hypoxia, and mammalian target of rapamycin (mTOR), were investigated in nine cohorts of patients with lung adenocarcinoma and five cohorts of patients with lung squamous cell carcinoma. The translation from gene signatures to a pathologic feature, tumor necrosis, was validated in The Cancer Genome Atlas lung adenocarcinoma cohort. The translation of signature score to pathway activity was further investigated by integrative analyses using The Cancer Genome Atlas and The Cancer Protein Atlas lung adenocarcinoma data sets. Results The results showed that the three gene signatures were mutually interdependent in lung adenocarcinoma but not in lung squamous cell carcinoma. The signature activities were higher in necrosis-positive tumors than in necrosis-negative tumors. The signature score correlated with the expression level of the representative protein that implicated the activity of each pathway. These signatures stratified patients with operable and stage I lung adenocarcinomas into different risk groups independent of age and stage. Furthermore, the signatures translated to a pathologic feature, tumor necrosis, which predicted shorter overall and relapse-free survival in patients with operable and stage I lung adenocarcinomas. Conclusion This study showed that gene signatures could translate into a pathologic feature, tumor necrosis, with risk stratification ability in patients with operable and stage I lung adenocarcinomas.

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Development of an Oncogenic Driver Alteration Associated Immune-Related Prognostic Model for Stage I-II Lung Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.593022 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jian-Zhao Xu ◽

Chen Gong ◽

Zheng-Fu Xie ◽

Hua Zhao

Keyword(s):

High Risk ◽

Mast Cells ◽

Tumor Microenvironment ◽

Lung Adenocarcinoma ◽

Prognostic Model ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Stage I ◽

Oncogenic Driver

Lung adenocarcinoma (LUAD) needs to be stratified for its heterogeneity. Oncogenic driver alterations such as EGFR mutation, ALK translocation, ROS1 translocation, and BRAF mutation predict response to treatment for LUAD. Since oncogenic driver alterations may modulate immune response in tumor microenvironment that may influence prognosis in LUAD, the effects of EGFR, ALK, ROS1, and BRAF alterations on tumor microenvironment remain unclear. Immune-related prognostic model associated with oncogenic driver alterations is needed. In this study, we performed the Cox-proportional Hazards Analysis based on the L1-penalized (LASSO) Analysis to establish an immune-related prognostic model (IPM) in stage I-II LUAD patients, which was based on 3 immune-related genes (PDE4B, RIPK2, and IFITM1) significantly enriched in patients without EGFR, ALK, ROS1, and BRAF alterations in The Cancer Genome Atlas (TCGA) database. Then, patients were categorized into high-risk and low-risk groups individually according to the IPM defined risk score. The predicting ability of the IPM was validated in GSE31210 and GSE26939 downloaded from the Gene Expression Omnibus (GEO) database. High-risk was significantly associated with lower overall survival (OS) rates in 3 independent stage I-II LUAD cohorts (all P < 0.05). Moreover, the IPM defined risk independently predicted OS for patients in TCGA stage I-II LUAD cohort (P = 0.011). High-risk group had significantly higher proportions of macrophages M1 and activated mast cells but lower proportions of memory B cells, resting CD4 memory T cells and resting mast cells than low-risk group (all P < 0.05). In addition, the high-risk group had a significantly lower expression of CTLA-4, PDCD1, HAVCR2, and TIGIT than the low-risk group (all P < 0.05). In summary, we established a novel IPM that could provide new biomarkers for risk stratification of stage I-II LUAD patients.

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Risk stratification model for patients with stage I invasive lung adenocarcinoma based on clinical and pathological predictors

Translational Lung Cancer Research ◽

10.21037/tlcr-21-393 ◽

2021 ◽

Vol 10 (5) ◽

pp. 2205-2217

Author(s):

Yiyang Wang ◽

Difan Zheng ◽

Jizhuang Luo ◽

Jie Zhang ◽

Cecilia Pompili ◽

...

Keyword(s):

Risk Stratification ◽

Lung Adenocarcinoma ◽

Stage I ◽

Risk Stratification Model ◽

Invasive Lung Adenocarcinoma

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A framework for risk stratification in EGFR+ lung adenocarcinoma treated with tyrosine kinase inhibitors

10.1055/s-0039-1678022 ◽

2019 ◽

Author(s):

P Christopoulos ◽

M Kirchner ◽

F Bozorgmehr ◽

N Magios ◽

AL Volckmar ◽

...

Keyword(s):

Risk Stratification ◽

Tyrosine Kinase ◽

Lung Adenocarcinoma ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors

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Faculty Opinions recommendation of Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤ 3 cm: accuracy and interobserver agreement.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718432386.793528488 ◽

2017 ◽

Author(s):

Paul Van Schil

Keyword(s):

Lung Adenocarcinoma ◽

Interobserver Agreement ◽

Frozen Section ◽

Stage I

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Faculty Opinions recommendation of Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.8166958.8577057 ◽

2011 ◽

Author(s):

Patrick Nana-Sinkam ◽

Michael Chacey

Keyword(s):

Lung Adenocarcinoma ◽

Stage I

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Development and validation of an individualized immune prognostic model in stage I–III lung squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-021-92115-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qi-Fan Yang ◽

Di Wu ◽

Jian Wang ◽

Li Ba ◽

Chen Tian ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Model ◽

Lung Squamous Cell Carcinoma ◽

Risk Groups ◽

Stage I ◽

Tissue Samples ◽

Mutation Burden

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

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