Prognostic Value and Therapeutic Potential of CBX Family Members in Ovarian Cancer

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Abstract

Background: Ovarian cancer (OV) is one of the common malignant tumors and has a poor prognosis. Chromobox (CBX) family proteins are critical components of epigenetic regulation complexes that repress target genes transcriptionally via chromatin modification. Some studies have investigated the function specifications among several CBXs members in multiple cancer types, however, little is known about the functions and prognostic roles of distinct CBXs family proteins in ovarian cancer.

Methods: In this study, several bioinformatics databases and in vitro experiments were used to analyze the expression profiles, prognostic values, and therapeutic potential of the CBXs family (CBX1-8) in ovarian cancer.

Results: It was found that higher expression of CBX3/8 and lower expression of CBX1/6/7 were detected in OV tissues. CBX2/4/5/8 were significantly correlated with individual cancer stages of OV. The expression of CBX1/2/3 were all significantly associated with worse overall survival (OS) and progression-free survival (PFS) for OV patients, whereas the expression of other five CBXs members showed either irrelevant (CBX5 and CBX8) or inconsistent (CBX4, CBX6, and CBX7) results for both OS and PFS in OV. These results showed that only CBX3 had consistent results in expression and prognosis. Further cell experiments also showed that CBX3 promoted the proliferation of ovarian cancer cells. CBX3 was highly expressed in chemoresistant OV tissues. These results indicated that CBX3 was the most likely prognostic indicator and new therapeutic target in OV. Furthermore, gene enrichment analysis suggests that the CBXs family was primarily involved in mast cell activation and mast cell mediated immunity. Individual CBXs members were associated with varying degrees of the infiltration of immune cells, especially B cells. Finally, a high genetic alteration rate of CBXs family (39%) was observed in OV. The low methylation status of CBX3/8 in OV may be associated with their high expression levels.

Conclusions: Taken together, these findings exhibited the pivotal value of CBXs family members (especially CBX3) in the prognosis and chemoresistance of ovarian cancer. Our results may provide new insight to explore new prognostic biomarkers and therapeutic targets for ovarian cancer.

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Cancer Statistics, 2021

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

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Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

J. Gao, B. A. Aksoy, U Dogrusoz … (2015)

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.

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UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

Darshan S. Chandrashekar, Bhuwan Bashel, Sai Balasubramanya … (2017)

Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. The large sample numbers in TCGA offer an excellent opportunity to address questions associated with tumo heterogeneity. Exploration of the data by cancer researchers and clinicians is imperative to unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed to aid researchers in carrying out specific TCGA data analyses; however there is need for resources to facilitate the study of gene expression variations and survival associations across tumors. Here, we report UALCAN, an easy to use, interactive web-portal to perform to in-depth analyses of TCGA gene expression data. UALCAN uses TCGA level 3 RNA-seq and clinical data from 31 cancer types. The portal's user-friendly features allow to perform: 1) analyze relative expression of a query gene(s) across tumor and normal samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinicopathologic features, 2) estimate the effect of gene expression level and clinicopathologic features on patient survival; and 3) identify the top over- and under-expressed (up and down-regulated) genes in individual cancer types. This resource serves as a platform for in silico validation of target genes and for identifying tumor sub-group specific candidate biomarkers. Thus, UALCAN web-portal could be extremely helpful in accelerating cancer research. UALCAN is publicly available at http://ualcan.path.uab.edu.

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Author and article information

Contributors

Kuan Hu: URI : https://loop.frontiersin.org/people/1179166/overview

Zhijie Xu: URI : https://loop.frontiersin.org/people/476407/overview

Yuanliang Yan: URI : https://loop.frontiersin.org/people/796195/overview

Juanni Li: URI : https://loop.frontiersin.org/people/974241/overview

Journal

Journal ID (nlm-ta): Front Cell Dev Biol

Journal ID (iso-abbrev): Front Cell Dev Biol

Journal ID (publisher-id): Front. Cell Dev. Biol.

Title: Frontiers in Cell and Developmental Biology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-634X

Publication date (Electronic): 27 January 2022

Publication date Collection: 2022

Volume: 10

Electronic Location Identifier: 832354

Affiliations

[1] ¹ Department of Hepatobiliary Surgery , Xiangya Hospital , Central South University , Changsha, China

[2] ² Department of Pathology , Xiangya Hospital , Central South University , Changsha, China

[3] ³ Department of Pharmacy , Xiangya Hospital , Central South University , Changsha, China

[4] ⁴ National Clinical Research Center for Geriatric Disorders , Xiangya Hospital , Central South University , Changsha, China

Author notes

Edited by: Dongling Zou, Chongqing University, China

Reviewed by: Xinyan Zhu, Tongji University, China

Lei Peng, Shandong University, China

Xi Cheng, Fudan University, China

*Correspondence: Juanni Li, lijuanni2014@ 123456csu.edu.cn ; Yuanliang Yan, yanyuanliang@ 123456csu.edu.cn

This article was submitted to Stem Cell Research, a section of the journal Frontiers in Cell and Developmental Biology

Article

Publisher ID: 832354

DOI: 10.3389/fcell.2022.832354

PMC ID: 8829121

PubMed ID: 35155439

SO-VID: 921cfbf0-8ea8-4b8c-ad80-62ad516ffb88

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 09 December 2021

Date accepted : 12 January 2022

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Award ID: 82103300 82102743

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Prognostic Value and Therapeutic Potential of CBX Family Members in Ovarian Cancer

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Most cited references 67

Cancer Statistics, 2021

Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses1

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