title: MAP3K3 expression in tumor cells and tumor-infiltrating lymphocytes is correlated with favorable patient survival in lung cancer.
abstract: MAP3K3 is involved in both the immune response and in tumor progression. Its potential biological role in vitro in lung cancer cell lines and the association of mRNA/protein expression patterns with clinical outcome of primary lung tumors were investigated in this study. Silencing MAP3K3 using siRNA in lung cancer cell lines resulted in decreased cell proliferation, migration and invasion. These effects were associated with down-regulation of the JNK, p38, AKT, and GSK3β pathways as determined using phospho-protein and gene expression array analyses. However, MAP3K3 mRNA and protein overexpression in primary lung tumors correlated significantly with favorable patient survival. Gene cluster and pathway analyses of primary tumor datasets indicated that genes positively-correlated with MAP3K3 are significantly involved in immune response rather than the cell cycle regulators observed using in vitro analyses. These results indicate that although MAP3K3 overexpression has an oncogenic role in vitro, in primary lung adenocarcinomas it correlates with an active immune response in the tumor environment that correlates with improved patient survival. MAP3K3 may potentially not only serve as diagnostic/prognostic markers for patients with lung cancer but also provide an indicator for future investigations into immunomodulatory therapies for lung cancer.
authors.affiliation: University of Guangzhou Chinese Medicine, Guangzhou, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: He
authors.affiliation: Guangxi Medical University, Nanning, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: The First People's Hospital of Yunnan Province, Kunming, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Xinjiang Medical University, Xinjiang, China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Xinjiang Medical University, Xinjiang, China.
authors.forename: Shengbin
authors.initials: S
authors.lastname: Bai
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Zhuwen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Rishindra M
authors.initials: RM
authors.lastname: Reddy
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Carrott
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Lynch
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Orringer
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, 48109, United States.
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D048748:MAP Kinase Kinase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048748:MAP Kinase Kinase Kinase 3; D038362:Glycogen Synthase Kinase 3; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases