TY - JOUR
T1 - SCGB2A1 is a novel prognostic marker for colorectal cancer associated with chemoresistance and radioresistance
AU - Munakata, Koji
AU - Uemura, Mamoru
AU - Takemasa, Ichiro
AU - Ozaki, Miyuki
AU - Konno, Masamitsu
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Mizushima, Tsunekazu
AU - Haraguchi, Naotsugu
AU - Noura, Shingo
AU - Ikenaga, Masakazu
AU - Okamura, S. H.U.
AU - Fukunaga, Mutsumi
AU - Murata, Kohei
AU - Yamamoto, Hirofumi
AU - Doki, Yuichiro
AU - Mori, Masaki
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899125219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899125219&partnerID=8YFLogxK
U2 - 10.3892/ijo.2014.2316
DO - 10.3892/ijo.2014.2316
M3 - Article
C2 - 24585249
AN - SCOPUS:84899125219
VL - 44
SP - 1521
EP - 1528
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 5
ER -