Department of Oral Pathology, Hospital of Stomatology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.
Institute of Oral Biomedicine, Heilongjiang Academy of Medical Science, Harbin, Heilongjiang 150086, China.
Cancer Biomark. 2019;26(1):11-20. doi: 10.3233/CBM-182009.
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.
PIWIL2 是一种人类 Argonaute 蛋白，它被小分子 RNA 引导至其靶标，在生殖细胞维持中发挥作用，并被提议在癌前干细胞和肿瘤干细胞中表达。然而，PIWIL2 表达在口腔癌和癌前病变中的意义尚未得到研究。在这项研究中，我们分析了口腔鳞状细胞癌（OSCC）和以恶性和癌前组织为主的癌前口腔白斑（OL）中干细胞蛋白 PIWIL2 的表达。在所评估的患者中，我们发现 PIWIL2 与 OSCC 预后和 OL 显著相关。此外，PIWIL2 被发现表达在肿瘤上皮细胞和肿瘤微环境中的巨噬细胞中，而这些细胞不是来自增大的淋巴结。细胞学实验证实，人鳞状细胞癌细胞系 SCC-25 可以促进 THP-1 细胞中 PIWIL2 和 Nanog 的水平，THP-1 细胞被广泛用于研究单核细胞和巨噬细胞的调节。我们的研究结果表明，PIWIL2 可以有效地预测 OSCC 预后和 OL，具有高度发展为 OSCC 的风险，并证实了口腔癌中的癌症干细胞（类）具有重新构成肿瘤异质性的能力，并导致不良结局和免疫抑制。
