Multiomics analysis reveals CT83 is the most specific gene for triple negative breast cancer and its hypomethylation is oncogenic in breast cancer

被引:19
作者
Chen, Chen [1 ]
Gao, Dan [1 ]
Huo, Jinlong [1 ]
Qu, Rui [1 ]
Guo, Youming [1 ]
Hu, Xiaochi [1 ]
Luo, Libo [1 ]
机构
[1] Zunyi Med Univ, Breast & Thyroid Ctr, Peoples Hosp Zunyi 1, Affiliated Hosp 3, Fenghuang N Rd, Zunyi 563000, Guizhou, Peoples R China
关键词
CANCER/TESTIS ANTIGENS EXPRESSION; DNA METHYLATION; TESTIS ANTIGENS; BASAL-LIKE; POTENTIAL BIOMARKERS; IMMUNOTHERAPY; SURVIVAL; KK-LC-1; TARGETS; LINE;
D O I
10.1038/s41598-021-91290-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer (BrC) subtype lacking effective therapeutic targets currently. The development of multi-omics databases facilities the identification of core genes for TNBC. Using TCGA-BRCA and METABRIC datasets, we identified CT83 as the most TNBC-specific gene. By further integrating FUSCC-TNBC, CCLE, TCGA pan-cancer, Expression Atlas, and Human Protein Atlas datasets, we found CT83 is frequently activated in TNBC and many other cancers, while it is always silenced in non-TNBC, 120 types of normal non-testis tissues, and 18 types of blood cells. Notably, according to the TCGA-BRCA methylation data, hypomethylation on chromosome X 116,463,019 to 116,463,039 is significantly correlated with the abnormal activation of CT83 in BrC. Using Kaplan-Meier Plotter, we demonstrated that activated CT83 is significantly associated with unfavorably overall survival in BrC and worse outcomes in some other cancers. Furthermore, GSEA suggested that the abnormal activation of CT83 in BrC is probably oncogenic by triggering the activation of cell cycle signaling. Meanwhile, we also noticed copy number variations and mutations of CT83 are quite rare in any cancer type, and its role in immune infiltration is not significant. In summary, we highlighted the significance of CT83 for TNBC and presented a comprehensive bioinformatics strategy for single-gene analysis in cancer.
引用
收藏
页数:14
相关论文
共 94 条
  • [1] Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?
    Al-Khadairi, Ghaneya
    Decock, Julie
    [J]. CANCERS, 2019, 11 (07)
  • [2] Basal-Like and Triple-Negative Breast Cancers Searching for Positives Among Many Negatives
    Alluri, Prasanna
    Newman, Lisa A.
    [J]. SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA, 2014, 23 (03) : 567 - +
  • [3] Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma
    Baba, Tetsuro
    Shiota, Hironobu
    Kuroda, Koji
    Shigematsu, Yoshiki
    Ichiki, Yoshinobu
    Uramoto, Hidetaka
    Hanagiri, Takeshi
    Tanaka, Fumihiro
    [J]. EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2013, 43 (04) : 759 - 764
  • [4] Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists
    Badve, Sunil
    Dabbs, David J.
    Schnitt, Stuart J.
    Baehner, Frederick L.
    Decker, Thomas
    Eusebi, Vincenzo
    Fox, Stephen B.
    Ichihara, Shu
    Jacquemier, Jocelyne
    Lakhani, Sunil R.
    Palacios, Jose
    Rakha, Emad A.
    Richardson, Andrea L.
    Schmitt, Fernando C.
    Tan, Puay-Hoon
    Tse, Gary M.
    Weigelt, Britta
    Ellis, Ian O.
    Reis-Filho, Jorge S.
    [J]. MODERN PATHOLOGY, 2011, 24 (02) : 157 - 167
  • [5] The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
    Barretina, Jordi
    Caponigro, Giordano
    Stransky, Nicolas
    Venkatesan, Kavitha
    Margolin, Adam A.
    Kim, Sungjoon
    Wilson, Christopher J.
    Lehar, Joseph
    Kryukov, Gregory V.
    Sonkin, Dmitriy
    Reddy, Anupama
    Liu, Manway
    Murray, Lauren
    Berger, Michael F.
    Monahan, John E.
    Morais, Paula
    Meltzer, Jodi
    Korejwa, Adam
    Jane-Valbuena, Judit
    Mapa, Felipa A.
    Thibault, Joseph
    Bric-Furlong, Eva
    Raman, Pichai
    Shipway, Aaron
    Engels, Ingo H.
    Cheng, Jill
    Yu, Guoying K.
    Yu, Jianjun
    Aspesi, Peter, Jr.
    de Silva, Melanie
    Jagtap, Kalpana
    Jones, Michael D.
    Wang, Li
    Hatton, Charles
    Palescandolo, Emanuele
    Gupta, Supriya
    Mahan, Scott
    Sougnez, Carrie
    Onofrio, Robert C.
    Liefeld, Ted
    MacConaill, Laura
    Winckler, Wendy
    Reich, Michael
    Li, Nanxin
    Mesirov, Jill P.
    Gabriel, Stacey B.
    Getz, Gad
    Ardlie, Kristin
    Chan, Vivien
    Myer, Vic E.
    [J]. NATURE, 2012, 483 (7391) : 603 - 607
  • [6] CDC25 phosphatases in cancer cells: key players? Good targets?
    Boutros, Rose
    Lobjois, Valerie
    Ducommun, Bernard
    [J]. NATURE REVIEWS CANCER, 2007, 7 (07) : 495 - 507
  • [7] The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
    Cerami, Ethan
    Gao, Jianjiong
    Dogrusoz, Ugur
    Gross, Benjamin E.
    Sumer, Selcuk Onur
    Aksoy, Buelent Arman
    Jacobsen, Anders
    Byrne, Caitlin J.
    Heuer, Michael L.
    Larsson, Erik
    Antipin, Yevgeniy
    Reva, Boris
    Goldberg, Arthur P.
    Sander, Chris
    Schultz, Nikolaus
    [J]. CANCER DISCOVERY, 2012, 2 (05) : 401 - 404
  • [8] Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers
    Chen, Fengju
    Chandrashekar, Darshan S.
    Varambally, Sooryanarayana
    Creighton, Chad J.
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [9] An Innovative Prognostic Model Based on Four Genes in Asian Patient with Gastric Cancer
    Chen, Jiahui
    Wang, Anqiang
    Ji, Jun
    Zhou, Kai
    Bu, Zhaode
    Lyu, Guoqing
    Ji, Jiafu
    [J]. CANCER RESEARCH AND TREATMENT, 2021, 53 (01): : 148 - 161
  • [10] Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling
    Chen, Zhiqiang
    Zuo, Xueliang
    Pu, Liyong
    Zhang, Yao
    Han, Guoyong
    Zhang, Long
    Wu, Zhengshan
    You, Wei
    Qin, Jianjie
    Dai, Xinzheng
    Shen, Hongbing
    Wang, Xuehao
    Wu, Jindao
    [J]. CELL PROLIFERATION, 2019, 52 (03)