Elevated expression of FREM1 in breast cancer indicates favorable prognosis and high‐level immune infiltration status

Autor: Zhi‐fang Yang, Xingrui Li, Zheng-tao Lv, Ge Wang, Han-ning Li, Miaomiao Cai
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Receptor
ErbB-2
Estrogen receptor
Breast Neoplasms
Metastasis
03 medical and health sciences
breast cancer
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
Immune system
Breast cancer
Databases
Genetic
Biomarkers
Tumor
medicine
Carcinoma
Humans
Radiology
Nuclear Medicine and imaging
Original Research
Cancer Biology
Neoplasm Staging
Tumor microenvironment
immune infiltration
business.industry
Estrogen Receptor alpha
Computational Biology
Receptors
Interleukin
Middle Aged
FRAS1‐Related Extracellular Matrix 1 (FREM1)
medicine.disease
Survival Rate
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
biomarker
Female
Triple-Negative Breast Carcinoma
prognosis
Neoplasm Grading
Receptors
Progesterone
business
Invasive Lobular Breast Carcinoma
Zdroj: Cancer Medicine
ISSN: 2045-7634
DOI: 10.1002/cam4.3543
Popis: Breast cancer (BC) poses one of the major threats to female's health worldwide. Immune infiltration in BC is a key representative of the tumor microenvironment and has been proven highly relevant for prognosis. The role of the FREM1 (FRAS1‐Related Extracellular Matrix 1) gene in carcinoma has not studied, moreover, the underlying mechanism remains largely unknown. This study aims to investigate the expression profile and potential action of FREM1 on BC progression. We applied series of bioinformatic methods as well as immunohistochemistry (IHC) and immunofluorescence (IF) to analyze FREM1 expression profile, its relationship with clinicopathological characteristics, impact on clinical outcomes, relevant functions, correlation with immune infiltration in BC. The results demonstrated that FREM1 had a dramatically reduced expression in BC tissues, possessed an inverse correlation with stage, age, and metastasis, and exhibited a higher level in invasive lobular breast carcinoma than in ductal one. Furthermore, decreased FREM1 expression was often associated with estrogen receptor (ER)/progesterone receptor (PR) negative and triple negative breast carcinoma (TNBC) status while human epidermal growth factor 2 (Her‐2) positive status, and considerably correlated with a worse overall survival (OS) and recurrence‐free survival (RFS). Meanwhile, the univariate/multivariate Cox model revealed that low‐FREM1 expression can be an independent prognostic factor for BC. Additionally, FREM1 was mainly involved in the cell metabolism and immune cells infiltration. Moreover, IHC and IF demonstrated a positive correlation of its expression with the immune infiltrating levels of CD4+, CD8+ T cells, and CD86+ M1 macrophages while a negative correlation with CD68+ pan‐macrophages and CD163+ M2 macrophages. These findings suggest that FREM1 can be a potential biomarker for evaluating the immune infiltrating status, and the BC prognosis.
This study aims to investigate the expression profile and potential action of FREM1 on BC tumorigenesis. We applied series of bioinformatic and statistical methods to analyze FREM1 expression profile, its diagnostic efficiency, relationship with clinicopathological characteristics, impact on clinical outcomes, relevant functions, correlation with immune infiltration in BC. We provide the first evidence that increased FREM1 expression correlates with favorable clinical outcomes and mediates the regulation of the function and recruitment of immune cells.
Databáze: OpenAIRE
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