SCGB2A1 is a novel prognostic marker for colorectal cancer associated with chemoresistance and radioresistance

Munakata,Koji; Uemura,Mamoru; Takemasa,Ichiro; Ozaki,Miyuki; Konno,Masamitsu; Nishimura,Junichi; Hata,Taishi; Mizushima,Tsunekazu; Haraguchi,Naotsugu; Noura,Shingo; Ikenaga,Masakazu; Okamura,Shu; Fukunaga,Mutsumi; Murata,Kohei; Yamamoto,Hirofumi; Doki,Yuichiro; Mori,Masaki

doi:10.3892/ijo.2014.2316

SCGB2A1 is a novel prognostic marker for colorectal cancer associated with chemoresistance and radioresistance

Authors:
- Koji Munakata
- Mamoru Uemura
- Ichiro Takemasa
- Miyuki Ozaki
- Masamitsu Konno
- Junichi Nishimura
- Taishi Hata
- Tsunekazu Mizushima
- Naotsugu Haraguchi
- Shingo Noura
- Masakazu Ikenaga
- Shu Okamura
- Mutsumi Fukunaga
- Kohei Murata
- Hirofumi Yamamoto
- Yuichiro Doki
- Masaki Mori
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan, Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Japan, Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan, Department of Surgery, Osaka Rosai Hospital, Japan, Department of Surgery, Suita Municipal Hospital, Japan, Department of Surgery, Sakai City Hospital, Japan
Published online on: February 28, 2014 https://doi.org/10.3892/ijo.2014.2316
Pages: 1521-1528

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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.

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