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CD74 和 HLA-DRA 在宫颈癌发生中的作用:抗肿瘤治疗的潜在靶点。

CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy.

机构信息

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Pulau Pinang, Malaysia.

Unit of Microbiology, Faculty of Medicine, AIMST University, Bedong 08100, Semeling, Malaysia.

出版信息

Medicina (Kaunas). 2022 Jan 26;58(2):190. doi: 10.3390/medicina58020190.

Abstract

: Abnormal expressions of CD74 and human leukocyte antigen-DR alpha (HLA-DRA) have been reported in various cancers, though their roles in cervical cancer remain unclear. This study aimed to evaluate the gene and protein expressions of CD74 and HLA-DRA in the progression from normal cervix to precancerous cervical intraepithelial neoplasia (CIN) and finally to squamous cell carcinoma (SCC). : The gene expression profiles of CD74 and HLA-DRA were determined in formalin-fixed paraffin-embedded tissues, with three samples each from normal cervixes, human papillomavirus type 16/18-positive, low-grade CIN (LGCIN), high-grade CIN (HGCIN), and squamous cell carcinoma (SCC) using Human Transcriptome Array 2.0. Immunohistochemical expression of the proteins was semi-quantitatively assessed in another cohort of tissue microarray samples comprising 7 normal cervix cases, 10 LGCIN, 10 HGCIN, and 95 SCC. : The transcriptomics profile and proteins' expression demonstrated similar trends of upregulation of CD74 and HLA-DRA from normal cervix to CIN and highest in SCC. There was a significant difference in both proteins' expression between the histological groups ( = 0.0001). CD74 and HLA-DRA expressions were significantly associated with CIN grade ( = 0.001 and = 0.030, respectively) but not with the subjects' age or SCC stage. Further analysis revealed a positive correlation between CD74 and HLA-DRA proteins. : CD74 appears to promote cervical carcinogenesis via oncogenic signalling mechanisms and may serve as a potential antitumour target. Additionally, the upregulation of HLA-DRA, often associated with stronger immunogenicity, could be a promising biomarker for developing immunotherapies.

摘要

CD74 和人类白细胞抗原-DR 阿尔法(HLA-DRA)的异常表达已在各种癌症中报道,尽管它们在宫颈癌中的作用尚不清楚。本研究旨在评估 CD74 和 HLA-DRA 的基因和蛋白表达在从正常宫颈到癌前宫颈上皮内瘤变(CIN)再到鳞状细胞癌(SCC)的进展过程中的作用。

使用 Human Transcriptome Array 2.0,在福尔马林固定石蜡包埋组织中确定了 CD74 和 HLA-DRA 的基因表达谱,每个样本来自正常宫颈、人乳头瘤病毒 16/18 阳性、低级别 CIN(LGCIN)、高级别 CIN(HGCIN)和鳞状细胞癌(SCC)各三个样本。在另一批组织微阵列样本中,通过免疫组织化学方法评估了蛋白质的半定量表达,该样本包括 7 例正常宫颈病例、10 例 LGCIN、10 例 HGCIN 和 95 例 SCC。

转录组学谱和蛋白质表达显示 CD74 和 HLA-DRA 的上调趋势相似,从正常宫颈到 CIN 逐渐升高,在 SCC 中最高。两种蛋白质的表达在组织学组之间存在显著差异( = 0.0001)。CD74 和 HLA-DRA 的表达与 CIN 分级显著相关( = 0.001 和 = 0.030),但与患者年龄或 SCC 分期无关。进一步分析显示 CD74 和 HLA-DRA 蛋白之间存在正相关。

CD74 似乎通过致癌信号机制促进宫颈癌的发生,可能成为潜在的抗肿瘤靶点。此外,HLA-DRA 的上调通常与更强的免疫原性相关,可能是开发免疫疗法的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cb/8877221/cbec383c72c6/medicina-58-00190-g001.jpg

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