CIP2A is a predictor of poor prognosis in colon cancer.
OBJECTIVE
The cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer.


METHODS
A tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyzed using the χ(2) test. Survival was analyzed using the Kaplan-Meier method. The impact of CIP2A on proliferation and drug resistance was evaluated using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide test. An anchorage-independent colony formation assay was also performed.


RESULTS
CIP2A was an independent prognostic factor in colon cancer after controlling for other clinical confounding factors, such as stage and lymphovascular invasion, particularly in stages III and IV (hazard ratio = 2.974, P < 0.001). The knockdown of CIP2A reduced the proliferation and anchorage-independent colony formation of colon cancer cells. Knockdown of CIP2A decreased the resistance of the cells to 5-fluorouracil, oxaliplatin, and SN38 (an active metabolite of irinotecan). Treatment with 5-fluorouracil, oxaliplatin, and SN38 decreased CIP2A expression.


CONCLUSIONS
CIP2A is a prognostic factor in colon cancer. The knockdown of CIP2A reduced proliferation and anchorage-independent colony formation and increased 5-fluorouracil, oxaliplatin, and SN38 efficacy in colon cancer cell lines.
Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Hao-Wei
HW
Teng
Shung-Haur
SH
Yang
Jen-Kou
JK
Lin
Wei-Shone
WS
Chen
Tzu-Chen
TC
Lin
Jeng-Kai
JK
Jiang
Chueh-Chuan
CC
Yen
Anna Fen-Yau
AF
Li
Paul Chih-Hsueh
PC
Chen
Yuan-Tzu
YT
Lan
Chun-Chi
CC
Lin
Yen-Ning
YN
Hsu
Hsei-Wei
HW
Wang
Kuen-Feng
KF
Chen
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D001324:Autoantigens / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001707:Biopsy, Needle; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D012334:RNA, Neoplasm / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001324:Autoantigens; D014408:Biomarkers, Tumor; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012334:RNA, Neoplasm