title: A Proteomic Study of Human Merkel Cell Carcinoma.
abstract: Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular events of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies.
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA ; Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Byrum
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Linley E
authors.initials: LE
authors.lastname: Moreland
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Mackintosh
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Kannan
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA ; Cancer Center Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: University of South Florida, College of Medicine, Tampa, FL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Stack
authors.affiliation: Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine in St. Louis, 63110, USA.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Cornelius
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
keywords: Liquid tissue platform; Merkel cell carcinoma; PI3K/mTOR pathway