eIF3C 过表达在预测肝内胆管癌预后中的作用。

Role of eIF3C Overexpression in Predicting Prognosis of Intrahepatic Cholangiocarcinoma.

机构信息

Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai, 200072, People's Republic of China.

Xiangya Medical College, Central South University, Changsha, 410008, Hunan, People's Republic of China.

出版信息

Dig Dis Sci. 2022 Feb;67(2):559-568. doi: 10.1007/s10620-021-06878-7. Epub 2021 Feb 12.

DOI:10.1007/s10620-021-06878-7

PMID:33576946

Abstract

BACKGROUND

Elevated expression of eukaryotic initiation factor 3c (eIF3C) was recently uncovered to promote several types of cancer progression by inducing cell proliferation. Here, we aimed to assess the expression and prognostic value of eIF3C in intrahepatic cholangiocarcinoma (ICC) patients.

METHODS

Expression of eIF3C was analyzed by immunohistochemistry in tissue microarrays (TMAs) containing 138 ICC and paired peritumoral tissues from ICC patients. Then, the roles of eIF3C in ICC cells were investigated by RNA interference, and the relationship between the eIF3C and KI67 expression was explored in ICC cells and tissues. Finally, the relation between the eIF3C level and clinicopathologic features of ICC was probed, and Kaplan-Meier and Cox's analyses were performed to assess the prognostic merit of eIF3C and KI67 in ICC patients.

RESULTS

The expression of eIF3C was elevated in ICC tissues compared to paired peritumoral tissues, which was consistent with the result from the GEPIA database. The downregulation of eIF3C in ICC cells impaired the cellular invasion, metastasis, colony formation, and proliferation. Moreover, we further found a positive relationship between the eIF3C and KI67 expression in ICC cells and tissues. The expression of eIF3C in ICC tissues was positively correlated with lymphatic metastasis (p = 0.049), and the high level of KI67 was frequently found in ICC patients with the large tumor (p = 0.028), high serum AFP (p = 0.019), or lymphatic metastasis (p = 0.039). Notably, patients with the eIF3C or KI67 overexpression had shorter overall survival and higher disease-free survival rates than those with low expression of eIF3C or KI67, and the combination of eIF3C or KI67 expression was an independent parameter for predicting the prognosis and recurrence of ICC patients.

CONCLUSIONS

Elevated eIF3C expression promotes ICC development, and combination of eIF3C and KI67 is a valuable predictor of the survival and recurrence of ICC patient.

摘要

背景

最近发现真核起始因子 3c（eIF3C）的高表达通过诱导细胞增殖促进多种类型的癌症进展。在这里，我们旨在评估 eIF3C 在肝内胆管癌（ICC）患者中的表达和预后价值。

方法

通过免疫组织化学分析包含 138 例 ICC 患者和配对肿瘤旁组织的组织微阵列（TMA）中 eIF3C 的表达。然后，通过 RNA 干扰研究 eIF3C 在 ICC 细胞中的作用，并在 ICC 细胞和组织中探索 eIF3C 与 KI67 表达的关系。最后，探讨了 eIF3C 水平与 ICC 临床病理特征的关系，并进行 Kaplan-Meier 和 Cox 分析以评估 eIF3C 和 KI67 在 ICC 患者中的预后价值。

结果

与配对的肿瘤旁组织相比，ICC 组织中 eIF3C 的表达升高，这与 GEPIA 数据库的结果一致。在 ICC 细胞中下调 eIF3C 会损害细胞侵袭、转移、集落形成和增殖。此外，我们还进一步发现 ICC 细胞和组织中 eIF3C 与 KI67 表达之间存在正相关关系。ICC 组织中 eIF3C 的表达与淋巴转移呈正相关（p=0.049），而在 ICC 患者中，大肿瘤（p=0.028）、高血清 AFP（p=0.019）或淋巴转移（p=0.039）时，常发现高 KI67 表达。值得注意的是，与 eIF3C 或 KI67 低表达的患者相比，eIF3C 或 KI67 过表达的患者总生存率和无病生存率更低，eIF3C 或 KI67 表达的组合是预测 ICC 患者预后和复发的独立参数。