An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer

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Abstract

Background: Immune-related long non-coding RNAs (irlncRNAs) might remodel the tumor immune microenvironment by changing the inherent properties of tumor cells and the expression of immune genes, which have been used to predict the efficacy of immunotherapy and the prognosis of various tumors. However, the value of irlncRNAs in breast cancer (BRCA) remains unclear.

Materials and Methods: Initially, transcriptome data and immune-related gene sets were downloaded from The Cancer Genome Atlas (TCGA) database. The irlncRNAs were extracted from the Immunology Database and Analysis Portal (ImmPort) database. Differently expressed irlncRNAs (DEirlncRNAs) were further identified by utilizing the limma R package. Then, univariate and multivariate Cox regression analyses were conducted to select the DEirlncRNAs associated with the prognosis of BRCA patients. In addition, the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to determine the DEirlncRNA pairs with the independent prediction capability of prognosis in BRCA patients. Finally, the chosen DEirlncRNA pair would be evaluated in terms of survival time, clinicopathological characteristics, tumor-infiltrating immune cells, immune checkpoints (ICs), signaling pathways, and potential small-molecule drugs.

Results: A total of 21 DEirlncRNA pairs were extracted, and among them, lncRNA MIR4435-2HG and lncRNA U62317.1 were chosen to establish a risk signature that served as an independent prognostic biomarker in BRCA patients. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they also had an abundance of infiltration of CD4 ⁺ T and CD8 ⁺ T cells to enhance the immune response to tumor cells. Furthermore, the risk signature showed a strong correlation with ICs, signaling pathways, and potential small-molecule drugs.

Conclusion: Our research revealed that the risk signature independent of specific DEirlncRNA pair expression was closely associated with the prognosis and tumor immune microenvironment in BRCA patients and had the potential to function as an independent prognostic biomarker and a predictor of immunotherapy for BRCA patients, which would provide new insights for BRCA accurate treatment.

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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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Extracellular matrix structure.

Achilleas Theocharis, Spyros Skandalis, Chrysostomi Gialeli … (2016)

Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

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CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance

Cheng Wang, Yang Li, Lingfei Jia … (2021)

Immunosurveillance is a critical mechanism guarding against tumor development and progression. Checkpoint inhibitors have shown significant success in cancer treatment, but expression of key factors such as PD-L1 in putative cancer stem cell (CSC) populations in squamous cell carcinoma has been inconclusive, suggesting that CSCs may have developed other mechanisms to escape immune surveillance. Here we show that CSCs upregulate the immune checkpoint molecule CD276 (B7-H3) to evade host immune responses. CD276 is highly expressed by CSCs in mouse and human head and neck squamous cell carcinoma (HNSCC) and can be used to prospectively isolate tumorigenic CSCs. Anti-CD276 antibodies eliminate CSCs in a CD8+ T cell-dependent manner, inhibiting tumor growth and lymph node metastases in a mouse HNSCC model. Single-cell RNA sequencing (RNA-seq) showed that CD276 blockade remodels SCC heterogeneity and reduces epithelial-mesenchymal transition. These results show that CSCs utilize CD276 for immune escape and suggest that targeting CD276 may reduce CSCs in HNSCC.

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Author and article information

Contributors

Hanwen Jiang: URI : https://loop.frontiersin.org/people/1820858/overview

Jingxian Sun: URI : https://loop.frontiersin.org/people/1264935/overview

Fucong Liu: URI : https://loop.frontiersin.org/people/1854224/overview

Xincai Wu: URI : https://loop.frontiersin.org/people/1854233/overview

Zhaohui Wen: URI : https://loop.frontiersin.org/people/1718333/overview

Journal

Journal ID (nlm-ta): Front Genet

Journal ID (iso-abbrev): Front Genet

Journal ID (publisher-id): Front. Genet.

Title: Frontiers in Genetics

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-8021

Publication date (Electronic): 22 June 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 895200

Affiliations

[1] ¹ Department of Neurology , Brain Ultrasound , The First Affiliated Hospital of Harbin Medical University , Harbin, China

[2] ² Department of Neurosurgery , The First Affiliated Hospital of Harbin Medical University , Harbin, China

Author notes

Edited by: Wenwen Zhang, Nanjing Medical University, China

Reviewed by: Dan Luo, Qilu Hospital, Shandong University, China

Mohamed Osama Ali Abdalla, Suez Canal University, Egypt

*Correspondence: Zhaohui Wen, wenzhaohui1968@ 123456163.com

[ † ]

These authors have contributed equally to this work

This article was submitted to Cancer Genetics and Oncogenomics, a section of the journal Frontiers in Genetics

Article

Publisher ID: 895200

DOI: 10.3389/fgene.2022.895200

PMC ID: 9257047

PubMed ID: 35812755

SO-VID: a4ad69e1-518f-422e-9afd-74e00cc73ea6

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 : 18 March 2022

Date accepted : 30 May 2022

Funding

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

An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer

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Abstract

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RNA drug delivery

Most cited references 53

Cancer Statistics, 2021

Extracellular matrix structure.

CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance

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