Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma

Background: Epithelial cell adhesion molecule (EpCAM), a well-established marker for circulating tumor cells, plays a crucial role in the complex process of cancer metastasis. The primary objective of this investigation is to study EpCAM expression in pan-cancer and elucidate its significance in the...

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Main Authors: Mei Chen, Yuanhui Gao, Hui Cao, Zhenting Wang, Shufang Zhang
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023107134
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author Mei Chen
Yuanhui Gao
Hui Cao
Zhenting Wang
Shufang Zhang
author_facet Mei Chen
Yuanhui Gao
Hui Cao
Zhenting Wang
Shufang Zhang
author_sort Mei Chen
collection DOAJ
description Background: Epithelial cell adhesion molecule (EpCAM), a well-established marker for circulating tumor cells, plays a crucial role in the complex process of cancer metastasis. The primary objective of this investigation is to study EpCAM expression in pan-cancer and elucidate its significance in the context of kidney renal clear cell carcinoma (KIRC). Methods: Data obtained from the public database was harnessed for the comprehensive assessment of the EpCAM expression levels and prognostic and clinicopathological correlations in thirty-three types of cancer. EpCAM was validated in our own KIRC sequencing and immunohistochemical cohorts. Subsequently, an in-depth exploration was conducted to scrutinize the interrelationship between EpCAM and various facets, including immune cells, immune checkpoints, and chemotherapy drugs. We employed Cox regression analysis to identify prognostic immunomodulators associated with EpCAM, which were subsequently utilized in the development of a prognostic model. The model was validated in our own clinical cohort and public datasets, and compared with 137 published models. The role of EpCAM in KIRC was explored by biological function experiments in vitro. Results: While EpCAM exhibited pronounced overexpression across a wide spectrum of cancer types, a notable reduction was observed in KIRC tissues. As grade increased, EpCAM expression decreased. EpCAM expression decreased in patients without metastasis. EpCAM mRNA and protein levels were used as independent, favorable prognostic factors in patients with KIRC in our own cohort. The expression of EpCAM exhibited strong associations with immune-related pathways, demonstrating an inverse correlation with the majority of immune cell types. Immune checkpoint inhibitors exert better therapeutic effects on patients with low EpCAM expression. In addition, EpCAM can be used as a drug resistance indicator and guide the clinical medication of patients with KIRC. A robust model, which had good predictive accuracy and applicability, showed significant superiority over other models. Importantly, EpCAM played the dual roles of promoting proliferation and resisting metastasis in KIRC. Conclusion: In the context of KIRC, EpCAM assumes a surprising dual role, where it not only facilitates cell proliferation but also exerts resistance against the metastatic process. EpCAM serves as a standalone prognostic marker for patients with KIRC, and related models can also effectively predict prognosis. These discoveries offer novel perspectives on the functional significance of EpCAM in the context of KIRC.
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spelling doaj.art-f47b83ce275a46bcb7d8fa5854d0c45e2024-02-01T06:32:11ZengElsevierHeliyon2405-84402024-01-01101e23505Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinomaMei Chen0Yuanhui Gao1Hui Cao2Zhenting Wang3Shufang Zhang4Central Laboratory, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, ChinaCentral Laboratory, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, ChinaCentral Laboratory, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, ChinaUrology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, China; Corresponding author.Central Laboratory, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, 570208, China; Corresponding author.Background: Epithelial cell adhesion molecule (EpCAM), a well-established marker for circulating tumor cells, plays a crucial role in the complex process of cancer metastasis. The primary objective of this investigation is to study EpCAM expression in pan-cancer and elucidate its significance in the context of kidney renal clear cell carcinoma (KIRC). Methods: Data obtained from the public database was harnessed for the comprehensive assessment of the EpCAM expression levels and prognostic and clinicopathological correlations in thirty-three types of cancer. EpCAM was validated in our own KIRC sequencing and immunohistochemical cohorts. Subsequently, an in-depth exploration was conducted to scrutinize the interrelationship between EpCAM and various facets, including immune cells, immune checkpoints, and chemotherapy drugs. We employed Cox regression analysis to identify prognostic immunomodulators associated with EpCAM, which were subsequently utilized in the development of a prognostic model. The model was validated in our own clinical cohort and public datasets, and compared with 137 published models. The role of EpCAM in KIRC was explored by biological function experiments in vitro. Results: While EpCAM exhibited pronounced overexpression across a wide spectrum of cancer types, a notable reduction was observed in KIRC tissues. As grade increased, EpCAM expression decreased. EpCAM expression decreased in patients without metastasis. EpCAM mRNA and protein levels were used as independent, favorable prognostic factors in patients with KIRC in our own cohort. The expression of EpCAM exhibited strong associations with immune-related pathways, demonstrating an inverse correlation with the majority of immune cell types. Immune checkpoint inhibitors exert better therapeutic effects on patients with low EpCAM expression. In addition, EpCAM can be used as a drug resistance indicator and guide the clinical medication of patients with KIRC. A robust model, which had good predictive accuracy and applicability, showed significant superiority over other models. Importantly, EpCAM played the dual roles of promoting proliferation and resisting metastasis in KIRC. Conclusion: In the context of KIRC, EpCAM assumes a surprising dual role, where it not only facilitates cell proliferation but also exerts resistance against the metastatic process. EpCAM serves as a standalone prognostic marker for patients with KIRC, and related models can also effectively predict prognosis. These discoveries offer novel perspectives on the functional significance of EpCAM in the context of KIRC.http://www.sciencedirect.com/science/article/pii/S2405844023107134EpCAMPan-cancerKidney renal clear cell carcinomaPrognosisProliferationMetastasis
spellingShingle Mei Chen
Yuanhui Gao
Hui Cao
Zhenting Wang
Shufang Zhang
Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
Heliyon
EpCAM
Pan-cancer
Kidney renal clear cell carcinoma
Prognosis
Proliferation
Metastasis
title Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
title_full Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
title_fullStr Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
title_full_unstemmed Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
title_short Comprehensive analysis reveals dual biological function roles of EpCAM in kidney renal clear cell carcinoma
title_sort comprehensive analysis reveals dual biological function roles of epcam in kidney renal clear cell carcinoma
topic EpCAM
Pan-cancer
Kidney renal clear cell carcinoma
Prognosis
Proliferation
Metastasis
url http://www.sciencedirect.com/science/article/pii/S2405844023107134
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