Expression of CIAPIN1 in human colorectal cancer and its correlation with prognosis.
BACKGROUND
The cytokine-induced anti-apoptotic molecule (CIAPIN1) had been found to be a differentially-expressed gene involved in a variety of cancers, and it was also considered as a candidate tumour suppressor gene in gastric cancer, renal cancer and liver cancer. However, studies on the role of CIAPIN1 in colorectal cancer were still unavailable. The aim of this study was to determine the prognostic impact of CIAPIN1 in 273 colorectal cancer (CRC) samples and to investigate the CIAPIN1 expression in CRC cell lines after inducing differentiation.


METHODS
Immunohistochemical analysis was performed to detect the expression of CIAPIN1 in CRC samples from 273 patients. The relationship between CIAPIN1 expression and patients' characteristics (gender, age, location of cancer, UICC stage, local recurrence and tumour grade factors) was evaluated. In addition, these patients were followed up for five consecutive years to investigate the relationship between CIAPIN1 expression and the prognosis of CRC. We induced the differentiation of the CRC cell lines HT29 and SW480, in order to detect the expression of CIAPIN1 in the process of CRC cells differentiation.


RESULTS
Results indicated that CIAPIN1 was mainly expressed in the cytoplasm and nucleus, and that its expression level in cancer samples was significantly lower than in normal tissues. The Wilcoxon-Mann-Whitney test showed a significant difference in the differential expression of CIAPIN1 in patients with different T and UICC stages, and tumour grade (P = 0.0393, 0.0297 and 0.0397, respectively). The Kaplan-Meier survival analysis demonstrated that the survival time of CRC patients with high expression of CIAPIN1 was longer than those with low expression during the 5-year follow up period (P = 0.0002). COX regression analysis indicated that low expression of CIAPIN1, cancer stage of > pT1, distant organ metastasis (pM1), regional lymph node metastasis (> pN1) and local recurrence (yes) were independent, poor prognostic factors of CRC (P = 0.012, P = 0.032, P <0.001, P <0.001, P <0.001 respectively). Both Western blotting and RT-PCR showed that CIAPIN1 expression was increased with the degree of differentiation of HT29 and SW480 cells.


CONCLUSIONS
CIAPIN1 played an important role in the differentiation of CRC cells, and the differential expression of CIAPIN1 in CRC was closely related to prognosis.
Shi
Hai
H
State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. weichang@fmmu.edu.cn
Zhou
Yi
Y
Liu
Heliang
H
Chen
Changsheng
C
Li
Shujun
S
Li
Nanlin
N
Li
Xiaohua
X
Zhang
Xi
X
Zhang
Hongwei
H
Wang
Weizhong
W
Zhao
Qingchuan
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
D014408:Biomarkers, Tumor; C489114:CIAPIN1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger
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