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Role of eIF3C Overexpression in Predicting Prognosis of Intrahepatic Cholangiocarcinoma

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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.

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Abbreviations

ICC:

Intrahepatic cholangiocarcinoma

eIF3C:

Eukaryotic translation initiation factor 3 subunit C

IHC:

Immunohistochemistry

TMA:

Tissue microarray

eIF4E:

Eukaryotic initiation factor 4E

OS:

Overall survival

DFS:

Disease-free survival

HCC:

Hepatocellular carcinoma

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Author notes

  1. Ya-Ping Xu and Ze-Ning Dong have contributed equally to this work.

Authors and Affiliations

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

    Ya-Ping Xu, Ying-Qun Zhou, Yu-Jie Zhao, Yan Zhao, Feng Wang & Chuan-Yong Guo

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

    Ze-Ning Dong

  3. Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China

    Ze-Ning Dong & Xiao-Yong Huang

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  1. Ya-Ping Xu
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Correspondence to Chuan-Yong Guo.

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Xu, YP., Dong, ZN., Zhou, YQ. et al. Role of eIF3C Overexpression in Predicting Prognosis of Intrahepatic Cholangiocarcinoma. Dig Dis Sci 67, 559–568 (2022). https://doi.org/10.1007/s10620-021-06878-7

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