State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
BMC Cancer. 2010 Sep 3;10:477. doi: 10.1186/1471-2407-10-477.
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.
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 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.
CIAPIN1 played an important role in the differentiation of CRC cells, and the differential expression of CIAPIN1 in CRC was closely related to prognosis.
细胞因子诱导的抗凋亡分子（CIAPIN1）已被发现是一种差异表达基因，参与多种癌症，并且被认为是胃癌、肾癌和肝癌中的候选肿瘤抑制基因。然而，CIAPIN1 在结直肠癌中的作用研究仍然缺乏。本研究的目的是确定 273 例结直肠癌（CRC）样本中 CIAPIN1 的预后影响，并研究 CRC 细胞系在诱导分化后 CIAPIN1 的表达。
采用免疫组织化学分析检测 273 例 CRC 患者样本中 CIAPIN1 的表达。评估 CIAPIN1 表达与患者特征（性别、年龄、癌症部位、UICC 分期、局部复发和肿瘤分级因素）之间的关系。此外，对这些患者进行了连续 5 年的随访，以研究 CIAPIN1 表达与 CRC 预后的关系。我们诱导 CRC 细胞系 HT29 和 SW480 的分化，以检测 CRC 细胞分化过程中 CIAPIN1 的表达。
结果表明，CIAPIN1 主要表达于细胞质和细胞核，且在癌组织样本中的表达水平明显低于正常组织。Wilcoxon-Mann-Whitney 检验显示，在不同 T 分期和 UICC 分期以及肿瘤分级的患者中，CIAPIN1 的差异表达有显著差异（P = 0.0393、0.0297 和 0.0397）。Kaplan-Meier 生存分析表明，在 5 年随访期间，CIAPIN1 高表达的 CRC 患者的生存时间长于低表达的患者（P = 0.0002）。COX 回归分析表明，CIAPIN1 低表达、肿瘤分期>pT1、远处器官转移（pM1）、区域淋巴结转移（>pN1）和局部复发（是）是 CRC 的独立不良预后因素（P = 0.012、P = 0.032、P<0.001、P<0.001、P<0.001）。Western blot 和 RT-PCR 均显示，随着 HT29 和 SW480 细胞分化程度的增加，CIAPIN1 的表达增加。
CIAPIN1 在 CRC 细胞分化中发挥重要作用，CIAPIN1 在 CRC 中的差异表达与预后密切相关。
