ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion

Background: Actin-related protein 2/3 complex subunit 2 (ARPC2) plays a fundamental role in actin filament nucleation and is critical for tumor cell migration and invasion. However, its abnormal expression, clinical significance, and biological function in human pan-cancer have been poorly explored....

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Main Authors: Shenglan Huang, Cairong Dong, Dan Li, Yongkang Xu, Jianbing Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.896080/full
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author Shenglan Huang
Shenglan Huang
Cairong Dong
Dan Li
Dan Li
Yongkang Xu
Yongkang Xu
Jianbing Wu
Jianbing Wu
author_facet Shenglan Huang
Shenglan Huang
Cairong Dong
Dan Li
Dan Li
Yongkang Xu
Yongkang Xu
Jianbing Wu
Jianbing Wu
author_sort Shenglan Huang
collection DOAJ
description Background: Actin-related protein 2/3 complex subunit 2 (ARPC2) plays a fundamental role in actin filament nucleation and is critical for tumor cell migration and invasion. However, its abnormal expression, clinical significance, and biological function in human pan-cancer have been poorly explored. Thus, we focused on ARPC2 as an entry point for identifying novel pan-cancer prognostic biomarkers.Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to assess the differential expression of ARPC2 in pan-cancer. The Human Protein Atlas was used for the tissue/cell-specific expression analysis of ARPC2. The genetic alteration information of ARPC2 was obtained from the cBioPortal database and the GSCALite platform. The prognostic value of ARPC2 was explored in pan-cancer using Cox regression and Kaplan–Meier analyses. Spearman correlation analysis was performed to investigate the relationship between ARPC2 expression and tumor mutational burden (TMB), DNA methyltransferases, microsatellite instability (MSI), immune-related genes, and mismatch repairs (MMRs). The ESTIMATE and CIBERSORT algorithms were used to evaluate the association between ARPC2 expression and the tumor microenvironment (TME) and immune infiltrating cells. We also conducted differential expression analysis of ARPC2 in hepatocellular carcinoma (HCC) tissues and cell lines using qPCR, western blotting, and immunohistochemistry and explored its role in tumor proliferation, migration, and invasion of HCC cells.Results: ARPC2 expression was significantly upregulated in multiple tumor types and significantly correlated with worse prognosis and higher clinicopathological stage. Genetic alterations and DNA methylation in tumor tissues may contribute to the aberrant expression of ARPC2. ARPC2 expression was significantly correlated with the tumor microenvironment (TME), infiltrating immune cells, TMB, microsatellite instability (MSI), and immune checkpoint-related genes in certain cancer types. In this experimental study, we found that the expression of ARPC2 was dramatically upregulated in HCC tissues and cell lines compared to adjacent liver tissues and normal liver cell lines. Functionally, ARPC2 silencing in HCC cells significantly inhibited cell proliferation, migration, and invasion, while the overexpression of ARPC2 promotes tumor proliferation, migration, and invasion.Conclusion: ARPC2 is a promising prognostic and immunological biomarker for multiple tumor types and is likely to play an important role in HCC progression and metastasis.
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spelling doaj.art-4a40a19099474568aff053bdf996692e2022-12-22T00:55:07ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-06-011010.3389/fcell.2022.896080896080ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and InvasionShenglan Huang0Shenglan Huang1Cairong Dong2Dan Li3Dan Li4Yongkang Xu5Yongkang Xu6Jianbing Wu7Jianbing Wu8Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, ChinaDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, ChinaDepartment of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, ChinaDepartment of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, ChinaBackground: Actin-related protein 2/3 complex subunit 2 (ARPC2) plays a fundamental role in actin filament nucleation and is critical for tumor cell migration and invasion. However, its abnormal expression, clinical significance, and biological function in human pan-cancer have been poorly explored. Thus, we focused on ARPC2 as an entry point for identifying novel pan-cancer prognostic biomarkers.Methods: The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to assess the differential expression of ARPC2 in pan-cancer. The Human Protein Atlas was used for the tissue/cell-specific expression analysis of ARPC2. The genetic alteration information of ARPC2 was obtained from the cBioPortal database and the GSCALite platform. The prognostic value of ARPC2 was explored in pan-cancer using Cox regression and Kaplan–Meier analyses. Spearman correlation analysis was performed to investigate the relationship between ARPC2 expression and tumor mutational burden (TMB), DNA methyltransferases, microsatellite instability (MSI), immune-related genes, and mismatch repairs (MMRs). The ESTIMATE and CIBERSORT algorithms were used to evaluate the association between ARPC2 expression and the tumor microenvironment (TME) and immune infiltrating cells. We also conducted differential expression analysis of ARPC2 in hepatocellular carcinoma (HCC) tissues and cell lines using qPCR, western blotting, and immunohistochemistry and explored its role in tumor proliferation, migration, and invasion of HCC cells.Results: ARPC2 expression was significantly upregulated in multiple tumor types and significantly correlated with worse prognosis and higher clinicopathological stage. Genetic alterations and DNA methylation in tumor tissues may contribute to the aberrant expression of ARPC2. ARPC2 expression was significantly correlated with the tumor microenvironment (TME), infiltrating immune cells, TMB, microsatellite instability (MSI), and immune checkpoint-related genes in certain cancer types. In this experimental study, we found that the expression of ARPC2 was dramatically upregulated in HCC tissues and cell lines compared to adjacent liver tissues and normal liver cell lines. Functionally, ARPC2 silencing in HCC cells significantly inhibited cell proliferation, migration, and invasion, while the overexpression of ARPC2 promotes tumor proliferation, migration, and invasion.Conclusion: ARPC2 is a promising prognostic and immunological biomarker for multiple tumor types and is likely to play an important role in HCC progression and metastasis.https://www.frontiersin.org/articles/10.3389/fcell.2022.896080/fullARPC2prognostic biomarkerimmune infiltratingpan-cancerhepatocellular carcinoma
spellingShingle Shenglan Huang
Shenglan Huang
Cairong Dong
Dan Li
Dan Li
Yongkang Xu
Yongkang Xu
Jianbing Wu
Jianbing Wu
ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
Frontiers in Cell and Developmental Biology
ARPC2
prognostic biomarker
immune infiltrating
pan-cancer
hepatocellular carcinoma
title ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
title_full ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
title_fullStr ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
title_full_unstemmed ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
title_short ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion
title_sort arpc2 a pan cancer prognostic and immunological biomarker that promotes hepatocellular carcinoma cell proliferation and invasion
topic ARPC2
prognostic biomarker
immune infiltrating
pan-cancer
hepatocellular carcinoma
url https://www.frontiersin.org/articles/10.3389/fcell.2022.896080/full
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