title: Fatty acid synthase overexpression confers an independent prognosticator and associates with radiation resistance in nasopharyngeal carcinoma.
abstract: Fatty acid synthase (FASN) is overexpressed in many human cancers and associated with poor prognosis. However, the role of FASN in nasopharyngeal carcinoma (NPC) has not been studied. We evaluated the expression of FASN immunohistochemically in 124 NPC specimens, stratified them into two groups (FASN-high and FASN-low), and examined the correlation with various clinicopathological parameters. In two NPC cell lines, HONE1 and TW01, we targeted the FASN transcript by shRNAi and evaluated the effect on cell proliferation by WST-1 assay and radiation-induced apoptosis by measuring caspase-3 and caspase-7 activation. NPC with high FASN immunoexpression was correlated with advanced pT disease status and worse prognosis in terms of disease-specific survival, metastasis-free survival and local recurrence-free survival, compared to FASN-low group in both univariate and multivariate analyses. In the two NPC cell lines, endogenous FASN expression was significantly higher than the non-tumor keratinocyte, DOK. When the expression of FASN was suppressed by shRNAi, the tumor cells showed decreased cell proliferation and increased apoptosis after radiation. Our results supported FASN as an adverse prognostic marker in NPC, possibly by conferring cell growth advantage and resistance to radiation-induced apoptosis on tumor cells. The inhibition of FASN expression might be investigated as an adjunct in treatment, especially in radiation resistant NPC.
authors.affiliation: Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Kao
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Li-Ching
authors.initials: LC
authors.lastname: Lin
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Hsu
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.forename: Tzu-Ju
authors.initials: TJ
authors.lastname: Chen
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D002277:Carcinoma; D049109:Cell Proliferation / Q000528:radiation effects*; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005720:Gamma Rays; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I