TY - JOUR
T1 - Elevated serum angiopoietin-like protein 2 correlates with the metastatic properties of colorectal cancer
T2 - A serum biomarker for early diagnosis and recurrence
AU - Toiyama, Yuji
AU - Tanaka, Koji
AU - Kitajima, Takahito
AU - Shimura, Tadanobu
AU - Kawamura, Mikio
AU - Kawamoto, Aya
AU - Okugawa, Yoshinaga
AU - Saigusa, Susumu
AU - Hiro, Junichiro
AU - Inoue, Yasuhiro
AU - Mohri, Yasuhiko
AU - Goel, Ajay
AU - Kusunoki, Masato
N1 - Publisher Copyright:
© 2014 AACR.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Purpose: Angiopoietin-like protein 2 (ANGPTL2) is a mediator of chronic inflammation and inflammatory carcinogenesis. The biologic and clinical significance of ANGPTL2 remains unknown in human cancer. Therefore, we investigated the function of ANGPTL2 and evaluated its clinical significance in both primary tumors and matched sera in patients with colorectal cancer.Experimental Design: A colorectal cancer cell line was transfected with siRNA against ANGPTL2 for the assessment of its function. We examined ANGPTL2 expression in colorectal cancer tissues (n 1/4 195) by immunohistochemistry. Finally, we screened serum ANGPTL2 levels from 32 colorectal cancers and 23 normal controls (NC), and validated these results in serum samples obtained from 195 colorectal cancers and 45 NCs by ELISA.Results: Knockdown of ANGPTL2 in vitro significantly inhibited cell proliferation, migration, and invasion, whereas it enhanced anoikis. ANGPTL2 was overexpressed in colorectal cancer tissues, and was significantly associated with advanced T stage, lymph node, and liver metastasis. Likewise, serum ANGPTL2 levels in colorectal cancers were significantly higher than NCs (P < 0.01), and allowed distinguishing of colorectal cancers from NCs with high accuracy (AUC 1/4 0.837). The subsequent validation step confirmed that serum ANGPTL2 levels in colorectal cancers were significantly higher than in NCs (P < 0.0001), and had a high AUC value (0.885) for distinguishing colorectal cancers from NCs. High serum ANGPTL2 was significantly associated with advanced T stage, lymph node and liver metastasis, early relapse, and poor prognosis in colorectal cancers.Conclusion: Serum ANGPTL2 is a novel diagnostic and recurrence-predictive biomarker in patients with colorectal cancer.
AB - Purpose: Angiopoietin-like protein 2 (ANGPTL2) is a mediator of chronic inflammation and inflammatory carcinogenesis. The biologic and clinical significance of ANGPTL2 remains unknown in human cancer. Therefore, we investigated the function of ANGPTL2 and evaluated its clinical significance in both primary tumors and matched sera in patients with colorectal cancer.Experimental Design: A colorectal cancer cell line was transfected with siRNA against ANGPTL2 for the assessment of its function. We examined ANGPTL2 expression in colorectal cancer tissues (n 1/4 195) by immunohistochemistry. Finally, we screened serum ANGPTL2 levels from 32 colorectal cancers and 23 normal controls (NC), and validated these results in serum samples obtained from 195 colorectal cancers and 45 NCs by ELISA.Results: Knockdown of ANGPTL2 in vitro significantly inhibited cell proliferation, migration, and invasion, whereas it enhanced anoikis. ANGPTL2 was overexpressed in colorectal cancer tissues, and was significantly associated with advanced T stage, lymph node, and liver metastasis. Likewise, serum ANGPTL2 levels in colorectal cancers were significantly higher than NCs (P < 0.01), and allowed distinguishing of colorectal cancers from NCs with high accuracy (AUC 1/4 0.837). The subsequent validation step confirmed that serum ANGPTL2 levels in colorectal cancers were significantly higher than in NCs (P < 0.0001), and had a high AUC value (0.885) for distinguishing colorectal cancers from NCs. High serum ANGPTL2 was significantly associated with advanced T stage, lymph node and liver metastasis, early relapse, and poor prognosis in colorectal cancers.Conclusion: Serum ANGPTL2 is a novel diagnostic and recurrence-predictive biomarker in patients with colorectal cancer.
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U2 - 10.1158/1078-0432.CCR-14-0007
DO - 10.1158/1078-0432.CCR-14-0007
M3 - Article
C2 - 25294915
AN - SCOPUS:84918517925
SN - 1078-0432
VL - 20
SP - 6175
EP - 6186
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -