J Cancer 2019; 10(15):3543-3552. doi:10.7150/jca.28364

Research Paper

Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma

Yi-Xiang Jin1#, Xiao-fen Zhou2,4#, Ying-ying Chen1#, Wen-xu Jin3, Ying-hao Wang2, Dan-rong Ye2,4, Yi-han Sun2,4, Yue-feng Li2,4, Qing-xuan Wang2, Xiao-Hua Zhang2, Ou-Chen Wang2✉, En-Dong Chen2✉

1. Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China
2. Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China
3. Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China
4. Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China
# These authors contributed equally to this work.

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Citation:
Jin YX, Zhou Xf, Chen Yy, Jin Wx, Wang Yh, Ye Dr, Sun Yh, Li Yf, Wang Qx, Zhang XH, Wang OC, Chen ED. Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma. J Cancer 2019; 10(15):3543-3552. doi:10.7150/jca.28364. Available from http://www.jcancer.org/v10p3543.htm

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Abstract

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene.

Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid.

Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell.

Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

Keywords: AKR1C2, Papillary thyroid carcinoma, Prognosis, Expression