RNA binding protein ZFP36 may be an important predictor of progression<b>-</b>free survival for papillary thyroid cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YAN Hao , XIE Jie , LU Xiubo ,  FAN Yuxia

Department of Thyroid Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, P. R. China;

Corresponding author：

FAN Yuxia, Email: doctorfyx@126.com

Keywords：

papillary thyroid cancer; RNA binding protein; ZFP36 gene

DOI：

10.7507/1007-9424.202112038

Video：

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Objective To screen prognosis prediction targets related to progression free survival (PFS) for patients with papillary thyroid cancer (PTC) based on the RNA binding proteins (RBPs) gene set. Methods The clinicopathologic data of patients with PTC were obtained from UCSC Xena database and the cancer tissues and paired tissue adjacent to cancer (a distance >2.0 cm) of the patients with PTC underwent thyroid surgery were obtained from the First Affiliated Hospital of Zhengzhou University. The differentially expressed RBPs genes between the cancer and normal tissues were determined from the comprehensive analysis of multiple public data sets, and the RBPs genes related to PFS were determined by univariate and multivariate Cox analyses. Western blot method was used to verify the protein expression of RBPs gene in the clinical cases. The RBPs genes with prognostic value and in combination with clinicopathologic parameters were use to establish a nomogram associated with prognostic prediction. Results ① A total of 424 patients with PTC were included from the UCSC Xena database and 30 patients with PTC were collected from the First Affiliated Hospital of Zhengzhou University. ② Seven down-regulated RBPs genes (ARHGEF28, IGF2BP2, KHDRBS2, MVP, PPARGC1A, SMAD9, TDRD9) and 3 up-regulated RBPs genes (ZFP36, ZFP36L2, ZMAT3) were identified in PTC. ③ The RBPs gene ZFP36 associated with PFS was screened by multivariate Cox analysis. ④ The Western blot result showed that the expression of ZFP36 protein was basically consistent with its gene expression. ⑤ The areas under the receiver operating characteristics curve of nomogram constructed in combination the clinicopathologic features related to PFS (M stage, T stage) with ZFP36 in predicting 1, 3, and 5-year PFS rates were 0.80 [95%CI (0.69, 0.91)], 0.72 [95%CI (0.62, 0.81)], and 0.64 [95%CI (0.50, 0.77)], respectively. The consistency index of nomogram was 0.724 [95%CI (0.685, 0.763)], and the calibration curve of the 3-year PFS probability was very close to the ideal diagonal. Conclusion According to the preliminary research results of database and clinical case data, RBPs ZFP36 might be a potential prognostic target for patients with PTC.

Citation： YAN Hao, XIE Jie, LU Xiubo, FAN Yuxia. RNA binding protein ZFP36 may be an important predictor of progression-free survival for papillary thyroid cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(9): 1195-1200. doi: 10.7507/1007-9424.202112038 Copy

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14.	McLeod DSA, Zhang L, Durante C, et al. Contemporary debates in adult papillary thyroid cancer management. Endocr Rev, 2019, 40(6): 1481-1499.
15.	Wang ZL, Li B, Luo YX, et al. Comprehensive genomic characterization of RNA-binding proteins across human cancers. Cell Rep, 2018, 22(1): 286-298.
16.	Pereira B, Billaud M, Almeida R. RNA-binding proteins in cancer: old players and new actors. Trends Cancer, 2017, 3(7): 506-528.
17.	Colombo C, Minna E, Gargiuli C, et al. The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer. J Exp Clin Cancer Res, 2020, 39（1）: 245. doi: 10.1186/s13046-020-01757-x.
18.	Liu H, Deng H, Zhao Y, et al. LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling. J Exp Clin Cancer Res, 2018, 37（1）: 279. doi: 10.1186/s13046-018-0950-9.
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21.	Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood, 2017, 129(21): 2857-2863.
22.	Xia W, Liu Y, Du Y, et al. MicroRNA-423 drug resistance and proliferation of breast cancer cells by targeting ZFP36. Onco Targets Ther, 2020, 13: 769-782.
23.	Zhu JG, Yuan DB, Chen WH, et al. Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer. Clin Transl Oncol, 2016, 18(8): 782-791.
24.	Zhang Z, Guo M, Li Y, et al. RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy, 2020, 16(8): 1482-1505.

1. Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet, 2016, 388(10061): 2783-2795.
2. Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2019, 30(12): 1856-1883.
3. Wang TS, Sosa JA. Thyroid surgery for differentiated thyroid cancer—recent advances and future directions. Nat Rev Endocrinol, 2018, 14(11): 670-683.
4. Qiu Z, Jiang H, Ju K, et al. A novel RNA-binding protein signature to predict clinical outcomes and guide clinical therapy in gastric cancer. Front Med （Lausanne）, 2021, 8: 670141. doi: 10.3389/fmed.2021.670141.
5. Xing Q, Luan JC, Liu SY, et al. Six RNA binding proteins （RBPs） related prognostic model predicts overall survival for clear cell renal cell carcinoma and it is associated with immune infiltration. Bosn J Basic Med Sci, 2021 Aug 22. doi: 10.17305/bjbms.2021.6097.
6. Zhen J, Song Z, Su W, et al. Integrated analysis of RNA-binding proteins in thyroid cancer. PLoS One, 2021, 16（3）: e0247836. doi: 10.1371/journal.pone.0247836.
7. Schlumberger M, Leboulleux S. Current practice in patients with differentiated thyroid cancer. Nat Rev Endocrinol, 2021, 17(3): 176-188.
8. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell, 2014, 159(3): 676-690.
9. Liu J, Lichtenberg T, Hoadley KA, et al. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell, 2018, 173(2): 400-416.
10. Gerstberger S, Hafner M, Tuschl T. A census of human RNA-binding proteins. Nat Rev Genet, 2014, 15(12): 829-845.
11. Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 2015, 43（7）: e47. doi: 10.1093/nar/gkv007.
12. Li L, Greene T, Hu B. A simple method to estimate the time-dependent receiver operating characteristic curve and the area under the curve with right censored data. Stat Methods Med Res, 2018, 27(8): 2264-2278.
13. Balachandran VP, Gonen M, Smith JJ, et al. Nomograms in oncology: more than meets the eye. Lancet Oncol, 2015, 16（4）: e173-e180. doi: 10.1016/S1470-2045（14）71116-7.
14. McLeod DSA, Zhang L, Durante C, et al. Contemporary debates in adult papillary thyroid cancer management. Endocr Rev, 2019, 40(6): 1481-1499.
15. Wang ZL, Li B, Luo YX, et al. Comprehensive genomic characterization of RNA-binding proteins across human cancers. Cell Rep, 2018, 22(1): 286-298.
16. Pereira B, Billaud M, Almeida R. RNA-binding proteins in cancer: old players and new actors. Trends Cancer, 2017, 3(7): 506-528.
17. Colombo C, Minna E, Gargiuli C, et al. The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer. J Exp Clin Cancer Res, 2020, 39（1）: 245. doi: 10.1186/s13046-020-01757-x.
18. Liu H, Deng H, Zhao Y, et al. LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling. J Exp Clin Cancer Res, 2018, 37（1）: 279. doi: 10.1186/s13046-018-0950-9.
19. Zhi J, Yi J, Tian M, et al. Immune gene signature delineates a subclass of thyroid cancer with unfavorable clinical outcomes. Aging (Albany NY), 2020, 12(7): 5733-5750.
20. Brooks SA, Blackshear PJ. Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim Biophys Acta, 2013, 1829(6-7): 666-679.
21. Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood, 2017, 129(21): 2857-2863.
22. Xia W, Liu Y, Du Y, et al. MicroRNA-423 drug resistance and proliferation of breast cancer cells by targeting ZFP36. Onco Targets Ther, 2020, 13: 769-782.
23. Zhu JG, Yuan DB, Chen WH, et al. Prognostic value of ZFP36 and SOCS3 expressions in human prostate cancer. Clin Transl Oncol, 2016, 18(8): 782-791.
24. Zhang Z, Guo M, Li Y, et al. RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy, 2020, 16(8): 1482-1505.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

RNA binding protein ZFP36 may be an important predictor of progression-free survival for papillary thyroid cancer

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