Identification of a prognostic index system and tumor immune infiltration characterization for lung adenocarcinoma based on mRNA molecular of pyroptosis

被引:1
作者
Li, Huawei [1 ]
Chang, Xiaoyan [1 ]
Wang, Haiyan [2 ]
Peng, Bo [1 ]
Wang, Jun [1 ]
Zhang, Pengfei [1 ]
Zhang, Linyou [1 ]
机构
[1] Harbin Med Univ, Dept Thorac Surg, Affiliated Hosp 2, Harbin, Heilongjiang, Peoples R China
[2] 83 Grp Mil Hosp Peoples Liberat Army, Dept Pediat, Xinxiang, Henan, Peoples R China
关键词
lung adenocarcinoma; pyroptosis; immunotherapy; PRMPI; OS; NATURAL-KILLER-CELLS; INFLAMMASOME ACTIVATION; NLRP3; INFLAMMASOME; T-CELLS; CANCER; DEATH; EXPRESSION; APOPTOSIS; CASPASE-8; SURVIVAL;
D O I
10.3389/fmed.2022.934835
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and purposePyroptosis is a form of programmed cell death, which plays an important role in tumorigenesis, progression, and regulation of the tumor microenvironment. It can affect lung adenocarcinoma (LUAD) progression. This study aimed to construct a pyroptosis-related mRNA prognostic index (PRMPI) for LUAD and clarify the tumor microenvironment infiltration characterization of LUAD. Materials and methodsWe performed a univariate Cox regression analysis for pyroptosis-related mRNAs in the TCGA cohort. Then, we used LASSO Cox regression to establish a PRMPI. The quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the relative expression of pyroptosis-related mRNAs. The CPTAC cohort was used to confirm the stability and wide applicability of the PRMPI. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the tumor microenvironment infiltration characterization. ResultsA total of 36 pyroptosis-related mRNAs were identified. The PRMPI was established based on five pyroptosis-related mRNAs. The expression patterns of these mRNAs were verified in LUAD samples from our medical center by qRT-PCR. High-PRMPI patients had worse overall survival than low-PRMPI patients. The result was validated in the CPTAC cohort. The comprehensive analysis indicated that the high-PRMPI patients exhibited lower immune activity, more aggressive immunophenotype, lower expression of immune checkpoint molecule, higher TP53 mutation rate, and higher tumor stemness than low-PRMPI patients. Low-PRMPI patients may be more sensitive to immunotherapy, while high-PRMPI patients may benefit more from chemotherapy and targeted therapy. ConclusionsThe PRMPI may be a promising biomarker to predict the prognosis, tumor microenvironment infiltration characterization, and the response to adjuvant therapy in LUAD.
引用
收藏
页数:15
相关论文
共 53 条
[1]   Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection [J].
Aachoui, Youssef ;
Sagulenko, Vitaliya ;
Miao, Edward A. ;
Stacey, Katryn J. .
CURRENT OPINION IN MICROBIOLOGY, 2013, 16 (03) :319-326
[2]   Role of natural killer cells in lung cancer [J].
Aktas, Ozge Nur ;
Ozturk, Ayse Bilge ;
Erman, Baran ;
Erus, Suat ;
Tanju, Serhan ;
Dilege, Sukru .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2018, 144 (06) :997-1003
[3]   The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer [J].
Allen, Irving C. ;
TeKippe, Erin McElvania ;
Woodford, Rita-Marie T. ;
Uronis, Joshua M. ;
Holl, Eda K. ;
Rogers, Arlin B. ;
Herfarth, Hans H. ;
Jobin, Christian ;
Ting, Jenny P. -Y. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (05) :1045-1056
[4]   IL-1 Family Members in Cancer; Two Sides to Every Story [J].
Baker, Kevin J. ;
Houston, Aileen ;
Brint, Elizabeth .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[5]   Emerging connectivity of programmed cell death pathways and its physiological implications [J].
Bedoui, Sammy ;
Herold, Marco J. ;
Strasser, Andreas .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2020, 21 (11) :678-695
[6]   Predicting survival from microarray data -: a comparative study [J].
Bovelstad, H. M. ;
Nygard, S. ;
Storvold, H. L. ;
Aldrin, M. ;
Borgan, O. ;
Frigessi, A. ;
Lingjaerde, O. C. .
BIOINFORMATICS, 2007, 23 (16) :2080-2087
[7]   The bed and the bugs: Interactions between the tumor microenvironment and cancer stem cells [J].
Castano, Zafira ;
Fillmore, Christine M. ;
Kim, Carla F. ;
McAllister, Sandra S. .
SEMINARS IN CANCER BIOLOGY, 2012, 22 (5-6) :462-470
[8]   Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade [J].
Charoentong, Pornpimol ;
Finotello, Francesca ;
Angelova, Mihaela ;
Mayer, Clemens ;
Efremova, Mirjana ;
Rieder, Dietmar ;
Hackl, Hubert ;
Trajanoski, Zlatko .
CELL REPORTS, 2017, 18 (01) :248-262
[9]   Tumour inflammasome-derived IL-1ß recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma [J].
Chen, Lih-Chyang ;
Wang, Li-Jie ;
Tsang, Nang-Ming ;
Ojcius, David M. ;
Chen, Chia-Chun ;
OuYang, Chun-Nan ;
Hsueh, Chuen ;
Liang, Ying ;
Chang, Kai-Ping ;
Chen, Chiu-Chin ;
Chang, Yu-Sun .
EMBO MOLECULAR MEDICINE, 2012, 4 (12) :1276-1293
[10]   Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion [J].
Ellis, Lixia Z. ;
Liu, Weimin ;
Luo, Yuchun ;
Okamoto, Miyako ;
Qu, Dovina ;
Dunn, Jeffrey H. ;
Fujita, Mayumi .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 414 (03) :551-556