title: Distinctive role of SIRT1 expression on tumor invasion and metastasis in breast cancer by molecular subtype.
abstract: The aim of this study was to evaluate silent mating type information regulation 2 homolog 1 (SIRT1) expression levels by subtype and evaluate its predictive power of axillary lymph node metastasis (LNM) and its association with clinical outcome. A total of 427 patients diagnosed with invasive ductal carcinoma were chosen, immunohistochemical staining for SIRT1 expression was performed on tissue microarrays, and in vitro experiments with each intrinsic subtype of human breast cancer cell line were carried out. Increased expression of SIRT1 in hormone receptor-positive breast cancer and HER2 breast cancer subtype significantly correlated with lower risks of LNM. On the contrary, in triple-negative breast cancer, increased SIRT1 expression was more frequently observed in LNM-positive subgroup than LNM-negative subgroup. Combination of statistically significant, independent parameters including SIRT1 revealed predictive performance for LNM with area under the curve of 0.602, 0.587, and 0.726 for hormone receptor-positive breast cancer, HER2 breast cancer, and triple-negative breast cancer subtype, respectively. Inhibition of SIRT1 expression with small interfering RNA suppressed tumor invasion in MDA-MB-231, specifically. This is the first study to examine SIRT1 expression in breast cancer by subtype, and we have observed the potentially different role of SIRT1 gene having tumor-suppressive or tumor-promoting influence depending on the subtype; thus, different associations between SIRT1 expression and prognosis by subtype should be considered in its target therapy.
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Yul Ri
authors.initials: YR
authors.lastname: Chung
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: In Ae
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Ja June
authors.initials: JJ
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 463-707 Seongnam-si, Gyeonggido, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyungkwan University School of Medicine, 135-710 Seoul, Republic of Korea.
authors.forename: Yoon Yang
authors.initials: YY
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Surgery, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Koung Jin
authors.initials: KJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Surgery, Seoul National University Hospital, 110-744 Seoul, Republic of Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Pathology, Seoul National University Hospital, 110-744 Seoul, Republic of Korea. Electronic address: karlnash@naver.com.
authors.forename: Han Suk
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D034622:RNA Interference; D012189:Retrospective Studies; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D014162:Transfection; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Breast cancer; Invasion; Metastasis; SIRT1; Subtype