Combination of Tumor Mutational Burden and DNA Damage Repair Gene Mutations with Stromal/Immune Scores Improved Prognosis Stratification in Patients with Lung Adenocarcinoma

被引:2
作者
Wu, Dongping [1 ]
Huang, Lingjuan [2 ]
Mao, Jiwei [1 ]
Liu, Jianjiang [1 ]
Ye, Wanli [1 ]
Xu, Jun [1 ]
Zhong, Wangyan [1 ]
Zhang, Xiaoyu [1 ]
Ying, Shenpeng [3 ]
机构
[1] Zhejiang Univ, Shaoxing Hosp, Shaoxing Peoples Hosp, Dept Radiat Oncol, Shaoxing 312000, Zhejiang, Peoples R China
[2] Zhejiang Univ, Shaoxing Peoples Hosp, Shaoxing Hosp, Dept Gen Surg, Shaoxing 312000, Zhejiang, Peoples R China
[3] Taizhou Univ, Taizhou Cent Hosp, Affiliated Hosp, Dept Radiat Oncol, Taizhou 318000, Zhejiang, Peoples R China
关键词
COMPREHENSIVE ANALYSIS; IMMUNOHISTOCHEMISTRY; SURVIVAL; LANDSCAPE; DOCETAXEL; ASSAYS; PD-L1;
D O I
10.1155/2022/6407344
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. Both the tumor environment and the genomic landscape of lung cancer may shape patient responses to treatments, including immunotherapy, but their joint impacts on lung adenocarcinoma (LUAD) prognosis are underexplored. Methods. RNA sequencing data and whole-exome sequencing results were downloaded from the TCGA database, and only LUAD-related data were included in this study. Based on gene expression data, the ESTIMATE algorithm was used to estimate stromal and immune scores, and CIBERSORT analysis was used for quantification of the relative abundances of immune cells. Somatic mutations were used for calculating tumor mutation burden (TMB). Specific mutations in genes involved in DNA damage repair (DDR) pathways were identified. The individual and joint associations of stromal and immune score, TMB, and DDR gene mutations with 5-year survival were analyzed by the Kaplan-Meier method and multivariate Cox model. Results. LUAD patients with a high (> highest 25%) stromal or immune score had prolonged survival as compared to those with a low (highest 25%) and low (< lowest 25%) TMB, or between patients with mutant-and wild-type DDR genes were not statistically significant, a survival benefit from high TMB or DDR gene mutations was observed in patients with high stromal or immune scores. Conclusion. A comprehensive evaluation of transcriptomic signatures and genomic biomarkers may provide a novel avenue for improving prognosis stratification in LUAD
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页数:12
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共 61 条
[1]   Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].
Brahmer, Julie ;
Reckamp, Karen L. ;
Baas, Paul ;
Crino, Lucio ;
Eberhardt, Wilfried E. E. ;
Poddubskaya, Elena ;
Antonia, Scott ;
Pluzanski, Adam ;
Vokes, Everett E. ;
Holgado, Esther ;
Waterhouse, David ;
Ready, Neal ;
Gainor, Justin ;
Aren Frontera, Osvaldo ;
Havel, Libor ;
Steins, Martin ;
Garassino, Marina C. ;
Aerts, Joachim G. ;
Domine, Manuel ;
Paz-Ares, Luis ;
Reck, Martin ;
Baudelet, Christine ;
Harbison, Christopher T. ;
Lestini, Brian ;
Spigel, David R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135
[2]   Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non-Small-Cell Lung Cancer [J].
Brambilla, Elisabeth ;
Le Teuff, Gwenael ;
Marguet, Sophie ;
Lantuejoul, Sylvie ;
Dunant, Ariane ;
Graziano, Stephen ;
Pirker, Robert ;
Douillard, Jean-Yves ;
Le Chevalier, Thierry ;
Filipits, Martin ;
Rosell, Rafael ;
Kratzke, Robert ;
Popper, Helmut ;
Soria, Jean-Charles ;
Shepherd, Frances A. ;
Seymour, Lesley ;
Tsao, Ming Sound .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (11) :1223-+
[3]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[4]   The Role of Tumor Stroma in Cancer Progression and Prognosis Emphasis on Carcinoma-Associated Fibroblasts and Non-small Cell Lung Cancer [J].
Bremnes, Roy M. ;
Donnem, Tom ;
Al-Saad, Samer ;
Al-Shibli, Khalid ;
Andersen, Sigve ;
Sirera, Rafael ;
Camps, Carlos ;
Marinez, Inigo ;
Busund, Lill-Tove .
JOURNAL OF THORACIC ONCOLOGY, 2011, 6 (01) :209-217
[5]   Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer [J].
Buttner, Reinhard ;
Gosney, John R. ;
Skov, Birgit Guldhammer ;
Adam, Julien ;
Motoi, Noriko ;
Bloom, Kenneth J. ;
Dietel, Manfred ;
Longshore, John W. ;
Lopez-Rios, Fernando ;
Penault-Llorca, Frederique ;
Viale, Giuseppe ;
Wotherspoon, Andrew C. ;
Kerr, Keith M. ;
Tsao, Ming-Sound .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (34) :3867-+
[6]   Comprehensive Analysis of Hypermutation in Human Cancer [J].
Campbell, Brittany B. ;
Light, Nicholas ;
Fabrizio, David ;
Zatzman, Matthew ;
Fuligni, Fabio ;
de Borja, Richard ;
Davidson, Scott ;
Edwards, Melissa ;
Elvin, Julia A. ;
Hodel, Karl P. ;
Zahurancik, Walter J. ;
Suo, Zucai ;
Lipman, Tatiana ;
Wimmer, Katharina ;
Kratz, Christian P. ;
Bowers, Daniel C. ;
Laetsch, Theodore W. ;
Dunn, Gavin P. ;
Johanns, Tanner M. ;
Grimmer, Matthew R. ;
Smirnov, Ivan V. ;
Larouche, Valerie ;
Samuel, David ;
Bronsema, Annika ;
Osborn, Michael ;
Stearns, Duncan ;
Raman, Pichai ;
Cole, Kristina A. ;
Storm, Phillip B. ;
Yalon, Michal ;
Opocher, Enrico ;
Mason, Gary ;
Thomas, Gregory A. ;
Sabel, Magnus ;
George, Ben ;
Ziegler, David S. ;
Lindhorst, Scott ;
Issai, Vanan Magimairajan ;
Constantini, Shlomi ;
Toledano, Helen ;
Elhasid, Ronit ;
Farah, Roula ;
Dvir, Rina ;
Dirks, Peter ;
Huang, Annie ;
Galati, Melissa A. ;
Chung, Jiil ;
Ramaswamy, Vijay ;
Irwin, Meredith S. ;
Aronson, Melyssa .
CELL, 2017, 171 (05) :1042-+
[7]   Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic [J].
Chan, T. A. ;
Yarchoan, M. ;
Jaffee, E. ;
Swanton, C. ;
Quezada, S. A. ;
Stenzinger, A. ;
Peters, S. .
ANNALS OF ONCOLOGY, 2019, 30 (01) :44-56
[8]   MULTIVARIATE SURVIVAL ANALYSIS USING COX REGRESSION-MODEL [J].
CHRISTENSEN, E .
HEPATOLOGY, 1987, 7 (06) :1346-1358
[9]   Immunotherapy in Non-Small Cell Lung Cancer: Facts and Hopes [J].
Doroshow, Deborah B. ;
Sanmamed, Miguel F. ;
Hastings, Katherine ;
Politi, Katerina ;
Rimm, David L. ;
Chen, Lieping ;
Melero, Ignacio ;
Schalper, Kurt A. ;
Herbst, Roy S. .
CLINICAL CANCER RESEARCH, 2019, 25 (15) :4592-4602
[10]   Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment [J].
Duma, Narjust ;
Santana-Davila, Rafael ;
Molina, Julian R. .
MAYO CLINIC PROCEEDINGS, 2019, 94 (08) :1623-1640