Clinicopathological characteristics, survival outcomes, and genetic alterations of younger patients with gastric cancer: Results from the China National Cancer Center and cBioPortal datasets

被引:10
作者
Niu, Penghui [1 ]
Huang, Huang [1 ]
Zhao, Lulu [1 ]
Wang, Tongbo [1 ]
Zhang, Xiaojie [1 ]
Wang, Wanqing [1 ]
Zhang, Yawei [1 ]
Guo, Chunguang [1 ]
Zhao, Dongbing [1 ]
Chen, Yingtai [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, Canc Hosp, 17 Panjiayuan Nanli, Beijing 100021, Peoples R China
基金
国家重点研发计划;
关键词
clinicopathological characteristics; gastric cancer; genetic alterations; survival outcomes; younger patient; METHYLTRANSFERASE KMT2D SUSTAINS; MORTALITY TRENDS; ADENOCARCINOMA; AGE; ACTIVATION; PROGNOSIS; MUTATION; GNAS; TRANSCRIPTION; EXPRESSION;
D O I
10.1002/cam4.4669
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background The survival outcomes of younger patients with gastric cancer (GC) have remained controversial. This study explores the clinicopathological characteristics, survival outcomes, and genetic alterations of younger and older patients with GC. Methods Patients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998-2018. Survival analysis was conducted using Kaplan-Meier estimates and Cox proportional hazards models. Sequencing datasets were enrolled from The Cancer Genome Atlas (TCGA) and Memorial Sloan-Kettering Cancer Center (MSKCC) databases. Results A total of 1146 younger (<40 years of age) and 16,988 older (>= 40 years of age) cases were included in the study. Younger patients had more poorly differentiated lesions than older patients (53.7% vs. 33.8%, respectively; p < 0.0001), and were more often pTNM stage IV (19.5% vs. 11.8%, respectively; p < 0.001). The 5-year overall survival (OS) of patients from the NCCGCDB increased from 1998 to 2018. Younger patients with pTNM stage III had a lower survival rate than older patients (p = 0.014), while no differences by age were observed at other stages. The mutation frequency of the LRP1B, GNAS, APC, and KMT2D genes was higher for older than younger patients (p < 0.05 for all genes). While not significantly different, younger patients from the TCGA and MSKCC databases were more likely to have CDH1, RHOA, and CTNNB1 gene mutations. Conclusions A stable proportion and improved survival of younger patients were reported using NCCGCDB data. Younger patients with pTNM stage III had lower rates of survival than older patients. Distinct molecular characteristics were identified in younger GC patients which may partly explain the histopathology and prognosis specific to this subpopulation.
引用
收藏
页码:3057 / 3073
页数:17
相关论文
共 61 条
[31]   Integrated molecular profiling of young and elderly patients with triple-negative breast cancer indicates different biological bases and clinical management strategies [J].
Ma, Ding ;
Jiang, Yi-Zhou ;
Xiao, Yi ;
Xie, Meng-Dan ;
Zhao, Shen ;
Jin, Xi ;
Xu, Xiao-En ;
Shao, Zhi-Ming .
CANCER, 2020, 126 (14) :3209-3218
[32]   Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum [J].
Matsubara, Akiko ;
Sekine, Shigeki ;
Kushima, Ryoji ;
Ogawa, Reiko ;
Taniguchi, Hirokazu ;
Tsuda, Hitoshi ;
Kanai, Yae .
JOURNAL OF PATHOLOGY, 2013, 229 (04) :579-587
[33]   SOMATIC MUTATION OF THE APC GENE IN GASTRIC-CANCER - FREQUENT MUTATIONS IN VERY WELL DIFFERENTIATED ADENOCARCINOMA AND SIGNET-RING CELL-CARCINOMA [J].
NAKATSURU, S ;
YANAGISAWA, A ;
ICHII, S ;
TAHARA, E ;
KATO, Y ;
NAKAMURA, Y ;
HORII, A .
HUMAN MOLECULAR GENETICS, 1992, 1 (08) :559-563
[34]   GNAS mutation as an alternative mechanism of activation of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of the fundic gland type [J].
Nomura, Ryosuke ;
Saito, Tsuyoshi ;
Mitomi, Hiroyuki ;
Hidaka, Yasuhiro ;
Lee, Se-yong ;
Watanabe, Sumio ;
Yao, Takashi .
HUMAN PATHOLOGY, 2014, 45 (12) :2488-2496
[35]   The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development [J].
Ortega-Molina, Ana ;
Boss, Isaac W. ;
Canela, Andres ;
Pan, Heng ;
Jiang, Yanwen ;
Zhao, Chunying ;
Jiang, Man ;
Hu, Deqing ;
Agirre, Xabier ;
Niesvizky, Itamar ;
Lee, Ji-Eun ;
Chen, Hua-Tang ;
Ennishi, Daisuke ;
Scott, David W. ;
Mottok, Anja ;
Hother, Christoffer ;
Liu, Shichong ;
Cao, Xing-Jun ;
Tam, Wayne ;
Shaknovich, Rita ;
Garcia, Benjamin A. ;
Gascoyne, Randy D. ;
Ge, Kai ;
Shilatifard, Ali ;
Elemento, Olivier ;
Nussenzweig, Andre ;
Melnick, Ari M. ;
Wendel, Hans-Guido .
NATURE MEDICINE, 2015, 21 (10) :1199-+
[36]   The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens [J].
Repana, Dimitra ;
Nulsen, Joel ;
Dressler, Lisa ;
Bortolomeazzi, Michele ;
Venkata, Santhilata Kuppili ;
Tourna, Aikaterini ;
Yakovleva, Anna ;
Palmieri, Tommaso ;
Ciccarelli, Francesca D. .
GENOME BIOLOGY, 2019, 20 (1)
[37]  
Saito H, 2012, YONAGO ACTA MED, V55, P57
[38]  
SANO T, 1991, CANCER RES, V51, P2926
[39]   Clinicopathologic and molecular features associated with patient age in gastric cancer [J].
Seo, Ji Yeon ;
Jin, Eun Hyo ;
Jo, Hyun Jin ;
Yoon, Hyuk ;
Shin, Cheol Min ;
Park, Young Soo ;
Kim, Nayoung ;
Jung, Hyun Chae ;
Lee, Dong Ho .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (22) :6905-6913
[40]   Health-Related Quality of Life of Adolescent and Young Adult Patients With Cancer in the United States: The Adolescent and Young Adult Health Outcomes and Patient Experience Study [J].
Smith, Ashley Wilder ;
Bellizzi, Keith M. ;
Keegan, Theresa H. M. ;
Zebrack, Brad ;
Chen, Vivien W. ;
Neale, Anne Victoria ;
Hamilton, Ann S. ;
Shnorhavorian, Margarett ;
Lynch, Charles F. .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (17) :2136-+