title: SCGB2A1 is a novel prognostic marker for colorectal cancer associated with chemoresistance and radioresistance.
abstract: We recently showed that liver metastatic tissue from patients with colorectal cancer (CRC) was a useful model for identifying novel, hypoxia-inducible genes and prognostic markers. We showed that the expression of secretoglobin, family 2A, member 1 (SCGB2A1) was a potential prognostic factor for CRC. Here, we further evaluated the prognostic impact and function of SCGB2A1 in 222 patients with CRC. The impact of SCGB2A1 expression on disease-free survival (DFS) and overall survival (OS) was assessed with mRNA expression profiling. The function of SCGB2A1 was analyzed by evaluating mRNA expression profiles in cells derived from patients with CRC and by testing the effects of transfecting SCGB2A1 into different CRC-derived cell lines. We evaluated the effects of SCGB2A1 on proliferation, chemosensitivity, radiation sensitivity and sphere formation. Univariate and multivariate analyses indicated that the expression of SCGB2A1 was an independent prognostic factor for CRC (p<0.05), together with lymph node metastasis (p<0.05). Enforced expression of SCGB2A1 in CRC-derived cell lines promoted proliferation (DLD1, SW480 and LoVo cells; p<0.05), decreased chemosensitivity to 5-fluorouracil and oxaliplatin (DLD1 and SW480 cell lines; p<0.05), and significantly increased the viability of irradiated cells (DLD1, SW480 and LoVo cell lines; p<0.05). SCGB2A1 expression was also correlated to cancer stemness-related genes (Wnt, Zeb1 and Twist). Consistent with this correlation, SCGB2A1 expressing cells (SW480) showed increased sphere formation (p<0.05). These results indicated that SCGB2A1 represented a novel, prognostic factor for CRC, and that expression of SCGB2A1 correlated with chemoresistance, radioresistance and cancer cell stemness.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Munakata
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ozaki
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Noura
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ikenaga
authors.affiliation: Department of Surgery, Suita Municipal Hospital, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Okamura
authors.affiliation: Department of Surgery, Sakai City Hospital, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Department of Surgery, Suita Municipal Hospital, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D060788:Mammaglobin B / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011836:Radiation Tolerance; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; D060788:Mammaglobin B; D009944:Organoplatinum Compounds; C556467:SCGB2A1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D051153:Wnt Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000077150:Oxaliplatin; D005472:Fluorouracil