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口腔上皮来源的白斑、发育异常及鳞状细胞癌中癌症干细胞生物标志物CD147的初步研究

Preliminary Study of the Cancer Stem Cells' Biomarker CD147 in Leukoplakia: Dysplasia and Squamous Cell Carcinoma of Oral Epithelial Origin.

作者信息

Zisis Vasileios, Andreadis Dimitrios, Anastasiadou Pinelopi, Vahtsevanos Konstantinos, Akrivou Meni, Vizirianakis Ioannis S, Poulopoulos Athanasios

机构信息

Oral Medicine/Pathology, Aristotle University of Thessaloniki, Thessaloniki, GRC.

Oral and Maxillofacial Surgery, Aristotle University of Thessaloniki, Thessaloniki, GRC.

出版信息

Cureus. 2023 May 9;15(5):e38807. doi: 10.7759/cureus.38807. eCollection 2023 May.

DOI:10.7759/cureus.38807
PMID:37303447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10256256/
Abstract

Objectives Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis de novo, as well as through the transformation of oral potential malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of our study was to detect the expression of stemness-type CSC marker CD147 in oral leukoplakias (OLs), the most common OPMD, and OSCCs as well. Materials and methods This study focuses on the semiquantitative immunohistochemical pattern of the expression of the CSC protein biomarker CD147 in paraffin-embedded samples of 20 OSCCs of different grades of differentiation and 30 cases of OLs without or with different grades of dysplasia, compared to the normal oral epithelium in terms of cells' stain positivity. Statistical analysis was performed through Statistical Package for Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) with Pearson chi-square test, and the significance level was set at 0.05 (p=0.05). In addition, the study clarified the expression of the respective gene of through quantitative polymerase chain (qPCR), in paraffin-embedded samples of the two extreme graduations: OLs of mildly dysplastic or non-dysplastic cases (n=10 cases) and OSCCs of moderately/poorly differentiated cases (n=17). Statistical analysis was then performed through SPSS version 25.0 with an independent paired t-test, and the significance level was set at 0.05 (p=0.05). Results The gene was expressed in all cases, although no statistically significant correlations were established. Regarding its protein products, the characteristic membranous staining of CD147 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. CD147 was upregulated significantly in the moderately and severely dysplastic OLs than in the mildly dysplastic and non-dysplastic OLs (p=0.008). Also, CD147 was upregulated significantly in the mildly dysplastic and non-dysplastic OLs than in the normal oral epithelium (p=0.012). Discussion The characteristic expression of CD147 in OLs and OSCCs' lesions suggests the presence of stemlike cancer cells, illustrating an underlying effect on the early stages of oral dysplasia, in the OL stage. The clinical application of CD147 as prognostic factor requires the experimental evaluation in larger number of samples. Conclusion Stem cells play an important role in the process of carcinogenesis. A major goal in cancer research is the identification of specific biomarkers for the detection of cancer stem cells. CD147 is considered as an innovative stem cell marker. Our findings in oral mucosal potentially malignant disorders showed that CD147 is expressed more intensely in parallel with the progression of the grade of dysplasia in OL. On the other hand, in oral squamous cell carcinoma, CD147 expression remains stable regardless of the degree of differentiation.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5906/10256256/edc3eb445719/cureus-0015-00000038807-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5906/10256256/edc3eb445719/cureus-0015-00000038807-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5906/10256256/edc3eb445719/cureus-0015-00000038807-i01.jpg
摘要

目的 癌症干细胞(CSCs)不仅负责从头启动致癌过程,还参与口腔潜在恶性病变(OPMDs)向口腔鳞状细胞癌(OSCC)的转化。我们研究的目的是检测干性类型的CSC标志物CD147在口腔白斑(OLs)(最常见的OPMD)以及OSCC中的表达。材料与方法 本研究聚焦于CSC蛋白生物标志物CD147在20例不同分化程度的OSCC石蜡包埋样本以及30例无发育异常或有不同程度发育异常的OL石蜡包埋样本中的半定量免疫组化表达模式,并与正常口腔上皮细胞的染色阳性情况进行比较。通过社会科学统计软件包(SPSS)25.0版(IBM SPSS Statistics,纽约州阿蒙克)进行统计分析,采用Pearson卡方检验,显著性水平设定为0.05(p = 0.05)。此外,该研究通过定量聚合酶链反应(qPCR)明确了两个极端分级的石蜡包埋样本中各自基因的表达情况:轻度发育异常或无发育异常的OL(n = 10例)和中/低分化的OSCC(n = 17例)。然后通过SPSS 25.0版进行独立配对t检验进行统计分析,显著性水平设定为0.05(p = 0.05)。结果 所有病例中均检测到该基因的表达,尽管未建立统计学上的显著相关性。关于其蛋白产物,在大多数样本中都观察到了CD147特征性的膜染色,主要在上皮细胞的基底层和副基底层。与轻度发育异常和无发育异常的OL相比,中度和重度发育异常的OL中CD147显著上调(p = 0.008)。此外,与正常口腔上皮相比,轻度发育异常和无发育异常的OL中CD147也显著上调(p = 0.012)。讨论 CD147在OL和OSCC病变中的特征性表达表明存在干细胞样癌细胞,这说明了在OL阶段对口腔发育异常早期阶段的潜在影响。将CD147作为预后因素的临床应用需要在更多样本中进行实验评估。结论 干细胞在致癌过程中起重要作用。癌症研究的一个主要目标是识别用于检测癌症干细胞的特定生物标志物。CD147被认为是一种创新性的干细胞标志物。我们在口腔黏膜潜在恶性病变中的研究结果表明,CD147的表达强度随着OL发育异常程度的进展而增加。另一方面,在口腔鳞状细胞癌中,无论分化程度如何,CD147的表达保持稳定。

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