Cross-cancer Prediction: A Novel Machine Learning Approach to Discover Molecular Targets for Development of Treatments for Multiple Cancers

被引:2
作者
Gao, Katie [1 ]
Wang, Dayong [2 ]
Huang, Yi [3 ]
机构
[1] Harvard Univ, 1483 Harvard Yard Mail CTR, Boston, MA 02138 USA
[2] PathAI Inc, Boston, MA USA
[3] Univ Maryland, Dept Math & Stat, Baltimore, MD 21250 USA
关键词
cross-cancer prediction; machine learning; molecular target; multi-cancer;
D O I
10.1177/1176935118805398
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Conventional cancer drug development has long been limited to organ- or tissue-specific cancer types. However, it has become increasingly known that specific genetic abnormalities are responsible for the carcinogenesis of multiple cancers. The recent US Food and Drug Administration (FDA) approval of the first multi-cancer drug, Keytruda. has demonstrated the feasibility of developing new drugs that target multiple cancers. Despite a promising future. methodological development for identifying multi-cancer molecular targets remains encumbered. This study developed a novel machine learning approach to identify such genes responsible for multiple cancers by synthesizing salient genomic information from cancer-specific classification models. This approach centered on the cross-cancer prediction method for identifying groups of cancers with high cross-cancer predictability. Furthermore, a robust hybrid classifier. comprising Prediction Analysis for Microarrays and Random Forest. was developed to integrate predictive models for gene inference. This approach has successfully identified key genes shared by endometrial cancer, mammary gland ductal carcinoma, and small cell lung cancer. The results are supported by published experimental evidence. This framework holds potential to transform the current methods of discovering multi-cancer molecular targets for clinical oncology.
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页数:8
相关论文
共 24 条
  • [1] TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells
    Azimi, Iman
    Milevskiy, Michael J. G.
    Kaemmerer, Elke
    Turner, Dane
    Yapa, Kunsala T. D. S.
    Brown, Melissa A.
    Thompson, Erik W.
    Roberts-Thomson, Sarah J.
    Monteith, Gregory R.
    [J]. JOURNAL OF CELL SCIENCE, 2017, 130 (14) : 2292 - 2305
  • [2] Targeting focal adhesion turnover in invasive breast cancer cells by the purine derivative reversine
    Bijian, K.
    Lougheed, C.
    Su, J.
    Xu, B.
    Yu, H.
    Wu, J. H.
    Riccio, K.
    Alaoui-Jamali, M. A.
    [J]. BRITISH JOURNAL OF CANCER, 2013, 109 (11) : 2810 - 2818
  • [3] Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
    Bolton, Kelly L.
    Chenevix-Trench, Georgia
    Goh, Cindy
    Sadetzki, Siegal
    Ramus, Susan J.
    Karlan, Beth Y.
    Lambrechts, Diether
    Despierre, Evelyn
    Barrowdale, Daniel
    McGuffog, Lesley
    Healey, Sue
    Easton, Douglas F.
    Sinilnikova, Olga
    Benitez, Javier
    Garcia, Maria J.
    Neuhausen, Susan
    Gail, Mitchell H.
    Hartge, Patricia
    Peock, Susan
    Frost, Debra
    Evans, Gareth
    Eeles, Rosalind
    Godwin, Andrew K.
    Daly, Mary B.
    Kwong, Ava
    Ma, Edmond S. K.
    Lazaro, Conxi
    Blanco, Ignacio
    Montagna, Marco
    D'Andrea, Emma
    Nicoletto, Maria Ornella
    Johnatty, Sharon E.
    Krueger, Susanne
    Jensen, Allan
    Hogdall, Estrid
    Goode, Ellen L.
    Fridley, Brooke L.
    Loud, Jennifer T.
    Greene, Mark H.
    Mai, Phuong L.
    Chetrit, Angela
    Lubin, Flora
    Hirsh-Yechezkel, Galit
    Glendon, Gord
    Andrulis, Irene L.
    Toland, Amanda E.
    Senter, Leigha
    Gore, Martin E.
    Gourley, Charlie
    Michie, Caroline O.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2012, 307 (04): : 382 - 390
  • [4] Prognosis of BRCA-associated breast cancer: a summary of evidence
    Bordeleau, L.
    Panchal, S.
    Goodwin, P.
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 2010, 119 (01) : 13 - 24
  • [5] Mitochondrial MKP1 Is a Target for Therapy-Resistant HER2-Positive Breast Cancer Cells
    Candas, Demet
    Lu, Chung-Ling
    Fan, Ming
    Chuang, Frank Y. S.
    Sweeney, Colleen
    Borowsky, Alexander D.
    Li, Jian Jian
    [J]. CANCER RESEARCH, 2014, 74 (24) : 7498 - 7509
  • [6] Ho TK, 1998, IEEE T PATTERN ANAL, V20, P832, DOI 10.1109/34.709601
  • [7] Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy
    Jiang, Hong
    Hegde, Samarth
    Knolhoff, Brett L.
    Zhu, Yu
    Herndon, John M.
    Meyer, Melissa A.
    Nywening, Timothy M.
    Hawkins, William G.
    Shapiro, Irina M.
    Weaver, David T.
    Pachter, Jonathan A.
    Wang-Gillam, Andrea
    DeNardo, David G.
    [J]. NATURE MEDICINE, 2016, 22 (08) : 851 - +
  • [8] KEGG: Kyoto Encyclopedia of Genes and Genomes
    Kanehisa, M
    Goto, S
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (01) : 27 - 30
  • [9] Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
    Kar, Siddhartha P.
    Beesley, Jonathan
    Al Olama, Ali Amin
    Michailidou, Kyriaki
    Tyrer, Jonathan
    Kote-Jarai, Zsofi A.
    Lawrenson, Kate
    Lindstrom, Sara
    Ramus, Susan J.
    Thompson, Deborah J.
    Kibel, Adam S.
    Dansonka-Mieszkowska, Agnieszka
    Michael, Agnieszka
    Dieffenbach, Aida K.
    Gentry-Maharaj, Aleksandra
    Whittemore, Alice S.
    Wolk, Alicja
    Monteiro, Alvaro
    Peixoto, Ana
    Kierzek, Andrzej
    Cox, Angela
    Rudolph, Anja
    Gonzalez-Neira, Anna
    Wu, Anna H.
    Lindblom, Annika
    Swerdlow, Anthony
    Ziogas, Argyrios
    Ekici, Arif B.
    Burwinkel, Barbara
    Karlan, Beth Y.
    Nordestgaard, Borge G.
    Blomqvist, Carl
    Phelan, Catherine
    McLean, Catriona
    Pearce, Celeste Leigh
    Vachon, Celine
    Cybulski, Cezary
    Slavov, Chavdar
    Stegmaier, Christa
    Maier, Christiane
    Ambrosone, Christine B.
    Hogdall, Claus K.
    Teerlink, Craig C.
    Kang, Daehee
    Tessier, Daniel C.
    Schaid, Daniel J.
    Stram, Daniel O.
    Cramer, Daniel W.
    Neal, David E.
    Eccles, Diana
    [J]. CANCER DISCOVERY, 2016, 6 (09) : 1052 - 1067
  • [10] Critical Role of TRPC1-Mediated Ca2+ Entry in Decidualization of Human Endometrial Stromal Cells
    Kawarabayashi, Yasuhiro
    Hai, Lin
    Honda, Akira
    Horiuchi, Shinji
    Tsujioka, Hiroshi
    Ichikawa, Jun
    Inoue, Ryuji
    [J]. MOLECULAR ENDOCRINOLOGY, 2012, 26 (05) : 846 - 858