Mitophagy-Related Gene Signature for Prediction Prognosis, Immune Scenery, Mutation, and Chemotherapy Response in Pancreatic Cancer

被引:24
作者
Zhuo, Zewei [1 ,2 ]
Lin, Hanying [3 ]
Liang, Jun [4 ]
Ma, Pengyue [5 ]
Li, Jingwei [2 ]
Huang, Lin [6 ]
Chen, Lishan [6 ]
Yang, Hongwei [7 ]
Bai, Yang [8 ]
Sha, Weihong [1 ,2 ]
机构
[1] South China Univ Technol, Sch Biosci & Bioengn, Guangzhou, Peoples R China
[2] Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Gastroenterol, Guangzhou, Peoples R China
[3] First Peoples Hosp Zhaoqing, Dept Endocrinol, Zhaoqing, Peoples R China
[4] Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Prov Geriatr Inst, Dept Geriatr,Intens Care Unit, Guangzhou, Peoples R China
[5] Zhengzhou Univ, Affiliated Hosp 2, Dept Nephrol, Zhengzhou, Peoples R China
[6] Guangdong Pharmaceut Univ, Sch Clin Med, Guangzhou, Peoples R China
[7] Guangzhou Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Guangzhou, Peoples R China
[8] Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Gastroenterol, Inst Gastroenterol Guangdong Prov,Dept Gastroente, Guangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
mitophagy; signature; prognosis; immune scenery; mutation; chemotherapy response; pancreatic cancer; EXPRESSION;
D O I
10.3389/fcell.2021.802528
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mitophagy is a conserved cellular process that plays a vital role in maintaining cellular homeostasis by selectively removing dysfunctional mitochondria. Notwithstanding that growing evidence suggests that mitophagy is implicated in pancreatic tumorigenesis, the effect of mitophagy-related genes on pancreatic cancer (PC) prognosis and therapeutic response remains largely unknown. In this study, we sought to construct a mitophagy-related gene signature and assessed its ability to predict the survival, immune activity, mutation status, and chemotherapy response of PC patients. During the screening process, we identified three mitophagy-related genes (PRKN, SRC, VDAC1) from The Cancer Genome Atlas (TCGA) cohort and a 3-gene signature was established. The prognostic model was validated using an International Cancer Genome Consortium (ICGC) cohort and two Gene Expression Omnibus (GEO) cohorts. According to the median risk score, PC patients were divided into high and low-risk groups, and the high-risk group correlated with worse survival in the four cohorts. The risk score was then identified as an independent prognostic predictor, and a predictive nomogram was constructed to guide clinical decision-making. Remarkably, enhanced immunosuppressive levels and higher mutation rates were observed in patients from the high-risk group, which may account for their poor survival. Furthermore, we found that high-risk patients were more sensitive to paclitaxel and erlotinib. In conclusion, a mitophagy-related gene signature is a novel prognostic model that can be used as a predictive indicator and allows prognostic stratification of PC patients.
引用
收藏
页数:17
相关论文
共 48 条
[1]   Synergistic Anti-Cancer Effects of AKT and SRC Inhibition in Human Pancreatic Cancer Cells [J].
Ahn, Kang ;
O, Young Moon ;
Ji, Young Geon ;
Cho, Han Jun ;
Lee, Dong Hyeon .
YONSEI MEDICAL JOURNAL, 2018, 59 (06) :727-735
[2]   ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity [J].
Alcala, Sonia ;
Sancho, Patricia ;
Martinelli, Paola ;
Navarro, Diego ;
Pedrero, Coral ;
Martin-Hijano, Laura ;
Valle, Sandra ;
Earl, Julie ;
Rodriguez-Serrano, Macarena ;
Ruiz-Canas, Laura ;
Rojas, Katerin ;
Carrato, Alfredo ;
Garcia-Bermejo, Laura ;
Angel Fernandez-Moreno, Miguel ;
Hermann, Patrick C. ;
Sainz Jr, Bruno .
NATURE COMMUNICATIONS, 2020, 11 (01)
[3]   The Immunoscore: Colon Cancer and Beyond [J].
Angell, Helen K. ;
Bruni, Daniela ;
Barrett, J. Carl ;
Herbst, Ronald ;
Galon, Jerome .
CLINICAL CANCER RESEARCH, 2020, 26 (02) :332-339
[4]   MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma [J].
Castillo, Lesley ;
Young, Adelaide I. J. ;
Mawson, Amanda ;
Schafranek, Pia ;
Steinmann, Angela M. ;
Nessem, Danielle ;
Parkin, Ashleigh ;
Johns, Amber ;
Chou, Angela ;
Law, Andrew M. K. ;
Lucas, Morghan C. ;
Murphy, Kendelle J. ;
Deng, Niantao ;
Gallego-Ortega, David ;
Caldon, Catherine E. ;
Timpson, Paul ;
Pajic, Marina ;
Ormandy, Christopher J. ;
Oakes, Samantha R. .
ONCOGENE, 2020, 39 (08) :1821-1829
[5]   Bioinformatics-Based Identification of Tumor Microenvironment-Related Prognostic Genes in Pancreatic Cancer [J].
Chen, Shaojie ;
Huang, Feifei ;
Chen, Shangxiang ;
Chen, Yinting ;
Li, Jiajia ;
Li, Yaqing ;
Lian, Guoda ;
Huang, Kaihong .
FRONTIERS IN GENETICS, 2021, 12
[6]   Macrophage Regulation of Tumor Responses to Anticancer Therapies [J].
De Palma, Michele ;
Lewis, Claire E. .
CANCER CELL, 2013, 23 (03) :277-286
[7]   Phage Display-Based Homing Peptide-Daunomycin Conjugates for Selective Drug Targeting to PANC-1 Pancreatic Cancer [J].
Dokus, Levente E. ;
Lajko, Eszter ;
Randelovic, Ivan ;
Mezo, Diana ;
Schlosser, Gitta ;
Kohidai, Laszlo ;
Tovari, Jozsef ;
Mezo, Gabor .
PHARMACEUTICS, 2020, 12 (06) :1-20
[8]   CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review [J].
Farhood, Bagher ;
Najafi, Masoud ;
Mortezaee, Keywan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (06) :8509-8521
[9]   Caspase-8 expression and its Src-dependent phosphorylation on Tyr380 promote cancer cell neoplastic transformation and resistance to anoikis [J].
Fianco, G. ;
Cenci, C. ;
Barila, D. .
EXPERIMENTAL CELL RESEARCH, 2016, 347 (01) :114-122
[10]   PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma [J].
Giuliani, Virginia ;
Miller, Meredith A. ;
Liu, Chiu-Yi ;
Hartono, Stella R. ;
Class, Caleb A. ;
Bristow, Christopher A. ;
Suzuki, Erika ;
Sanz, Lionel A. ;
Gao, Guang ;
Gay, Jason P. ;
Feng, Ningping ;
Rose, Johnathon L. ;
Tomihara, Hideo ;
Daniele, Joseph R. ;
Peoples, Michael D. ;
Bardenhagen, Jennifer P. ;
Geck Do, Mary K. ;
Chang, Qing E. ;
Vangamudi, Bhavatarini ;
Vellano, Christopher ;
Ying, Haoqiang ;
Deem, Angela K. ;
Do, Kim-Anh ;
Genovese, Giannicola ;
Marszalek, Joseph R. ;
Kovacs, Jeffrey J. ;
Kim, Michael ;
Fleming, Jason B. ;
Guccione, Ernesto ;
Viale, Andrea ;
Maitra, Anirban ;
Emilia Di Francesco, M. ;
Yap, Timothy A. ;
Jones, Philip ;
Draetta, Giulio ;
Carugo, Alessandro ;
Chedin, Frederic ;
Heffernan, Timothy P. .
NATURE COMMUNICATIONS, 2021, 12 (01)