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上皮性卵巢癌中间质转化标志物与 EGFR 表达的相关性及其预后价值。

Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients.

机构信息

Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

出版信息

Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4213-4225. doi: 10.31557/APJCP.2022.23.12.4213.

DOI:10.31557/APJCP.2022.23.12.4213
PMID:36580004
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9971466/
Abstract

BACKGROUND

CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC).

METHODS

This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification.

RESULTS

High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030).  CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000).

CONCLUSION

EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.

摘要

背景

CD44 是上皮-间质转化(EMT)表面受体,调节细胞与细胞外基质之间的相互作用,从而促进细胞迁移。表皮生长因子受体(EGFR)家族是一种跨膜激酶相关蛋白。它调节细胞黏附蛋白,可能促进细胞增殖和侵袭性。间质上皮转化(MET)是另一种 EMT 受体,刺激细胞增殖、侵袭、存活和血管生成。本研究旨在评估 CD44、EGFR 表达和 MET 基因扩增对上皮性卵巢癌(EOC)的预后影响。

方法

这是一项回顾性队列研究,包括 85 例 EOC 病例。通过免疫组织化学评估上皮和基质细胞中 CD44 和 EGFR 的表达。肿瘤细胞还通过荧光原位杂交(FISH)进行细胞遗传学分析,以检测 MET 基因扩增。

结果

肿瘤中 CD44 高表达与浆液性亚型显著相关(P=0.001)、腹膜沉积物(P=0.002)和晚期(P=0.002)。EGFR 高肿瘤表达与淋巴结转移(P=0.038)和 EOC 晚期显著相关(P=0.016)。MET 基因拷贝数增加与部分治疗反应显著相关(P=0.030)。CD44 和 EGFR 肿瘤高表达与总生存(OS)不良相关。此外,肿瘤中 MET 基因增益与较短的 OS 相关(P=0.000)。

结论

EOC 中的 EMT 生物标志物(CD44 和 MET)和 EGFR 表达是 OS 的独立预后因素。MET 基因拷贝数增加在浆液性肿瘤中检测到,与不良生存和最小治疗反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/e5eea2f08876/APJCP-23-4213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/953c5e68278b/APJCP-23-4213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/0240f485dc80/APJCP-23-4213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/a417d2eba01c/APJCP-23-4213-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/d5947e304b0d/APJCP-23-4213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/e5eea2f08876/APJCP-23-4213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/953c5e68278b/APJCP-23-4213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/0240f485dc80/APJCP-23-4213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/a417d2eba01c/APJCP-23-4213-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/d5947e304b0d/APJCP-23-4213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/127a/9971466/e5eea2f08876/APJCP-23-4213-g005.jpg

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