Expression of PIWIL2 in oral cancer and leukoplakia: Prognostic implications and insights from tumors

Article type: Research Article

Authors: Wang, Shan^{a; f; *} | Li, Fang^b | Fan, Haixia^c | Xu, Jiankai^{d; *} | Hu, Zheng^e

Affiliations: [a] Department of Oral Pathology, Hospital of Stomatology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China | [b] Department of Oral and Maxillofacial Surgery, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150001, China | [c] Department of Oral Medicine, Jining Medical College, Jining, Shandong 272067, China | [d] College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China | [e] Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, Heilongjiang 150080, China | [f] Institute of Oral Biomedicine, Heilongjiang Academy of Medical Science, Harbin, Heilongjiang 150086, China

Correspondence: [*] Corresponding authors: Shan Wang, Department of Oral Pathology, Hospital of Stomatology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China. Tel.: +86 451 85553807; E-mail: birchtree20032003@126.com. Jiankai Xu, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China. Tel.: +86 451 86620941; E-mail: jxu@ems.hrbmu.edu.cn.

Abstract: PIWIL2 is a human Argonaute protein, which is guided by small RNAs to its targets, plays a role in germ cell maintenance and has been proposed to be expressed in precancerous stem cells and tumor stem cells. However, the significance of PIWIL2 expression in oral cancer and precancerous lesions has not been investigated. In this study, we analyzed the expression of the stem cell protein PIWIL2 in oral squamous-cell carcinoma (OSCC) and in premalignant oral leukoplakia (OL) with predominant expression in malignant and premalignant tissues. In the evaluated patients, we found that PIWIL2 was associated significantly with OSCC prognosis and OL. Furthermore, PIWIL2 was found to be expressed in tumor epithelial cells and macrophages in the tumor microenvironment, which are not derived from enlarged lymph nodes. Cytological experiments confirmed that the human squamous cell carcinoma cell line SCC-25, can promote the PIWIL2 and Nanog level in THP-1 cells, which are extensively used to study the modulation of monocytes and macrophages. Our findings showed that PIWIL2 can predict effectively OSCC prognosis and OL with a high risk of OSCC development and substantiate the deduction that cancer stem(-like) cells in oral cancer have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to poor outcome and immunosuppression.

Keywords: PIWIL2, oral cancer, leukoplakia, prognosis, tumor microenvironment

DOI: 10.3233/CBM-182009

Journal: Cancer Biomarkers, vol. 26, no. 1, pp. 11-20, 2019