J Cancer 2020; 11(17):5162-5176. doi:10.7150/jca.45604

Research Paper

The correlation and role analysis of KCNK2/4/5/15 in Human Papillary Thyroid Carcinoma microenvironment

Xu Lin1, Jing-Fang Wu1✉, Dong-Mei Wang1, Jing Zhang1, Wen-Jing Zhang1, Gang Xue2✉

1. Department of Histology and Embryology, Hebei North University, Zhangjiakou, 075000, China.
2. Department of Otorhinolaryngology Head and Neck Surgery, Hebei North University, Zhangjiakou, 075000, China.

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Citation:
Lin X, Wu JF, Wang DM, Zhang J, Zhang WJ, Xue G. The correlation and role analysis of KCNK2/4/5/15 in Human Papillary Thyroid Carcinoma microenvironment. J Cancer 2020; 11(17):5162-5176. doi:10.7150/jca.45604. Available from https://www.jcancer.org/v11p5162.htm

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Abstract

Background: KCNKs, potassium two pore domain channel family K members, can maintain the resting potential, regulate the amplitude and duration of the plateau of the action potential, and change the membrane potential and membrane excitability. Evidence from many studies indicates that KCNKs is abnormally expressed in many solid tumors and plays a regulatory role in the development and malignant progression of cancer. However, the expression pattern and prognostic value of KCNK factors in papillary thyroid carcinoma have not been reported.

Methods: In this study, we used the data from databases such as ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal to perform bioinformatics analysis of KCNK factors in patients with thyroid cancer.

Results: We found that the mRNA expression of KCNK1, KCNK5, KCNK6, KCNK7, and KCNK15 were significantly higher in thyroid cancer tissues than that in normal tissues, while KCNK2, KCNK4, KCNK9, KCNK16 and KCNK17 mRNA levels were decreased compared to normal tissues. And the expression levels of KCNK1/2/4/5/6/7/15 were correlated with the tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that KCNK2/3/4/5/12/15 were associated with overall survival (OS) in patients with thyroid cancer.

Conclusion: Finally, the results of ROC curves, immunohistochemical staining, immune cell infiltration and kinase / miRNA / transcription factor regulation showed that KCNK2, KCNK4, KCNK5 and KCNK15 levels could be used as biomarkers for PTC diagnosis. This study implied that KCNK2, KCNK4, KCNK5 and KCNK15 are potential targets of precision therapy for patients with thyroid cancer and these genes are new biomarkers for the therapeutic target for thyroid cancer.

Keywords: papillary thyroid carcinoma, KCKNs, microenvironment, immune cell infiltration