Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features

Llanos, Adana A.M.; Yao, Song; Singh, Amartya; Aremu, John B.; Khiabanian, Hossein; Lin, Yong; Omene, Coral; Omilian, Angela R.; Khoury, Thaer; Hong, Chi-Chen; Ganesan, Shridar; Foran, David J.; Higgins, Michael J.; Ambrosone, Christine B.; Bandera, Elisa V.; Demissie, Kitaw

doi:10.1007/s10549-020-05972-0

Cited by 14 publications

(20 citation statements)

References 35 publications

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“…These findings suggested possible links between LEP expression and OC, however, the exact mechanism of this gene and its potential prognostic value remain unclear. Furthermore, several studies have investigated the protein expression pattern of LEP in tissues of many cancer types such as breast [ 59 , 60 ] and colorectal cancer [ 61 ], but only one study had assessed the clinical value of LEP and its associated receptor (Ob-R) in OC patients from the Middle-East region [ 62 ]. In the current study, we evaluated the protein expression of LEP in OC tissues, its correlation with the LEP promoter methylation status, and its potential prognostic value.…”

Section: Discussionmentioning

confidence: 99%

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Assidi

Yahya

Al-Zahrani

et al. 2021

IJMS

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Ovarian cancer (OC) is the deadliest among all gynecological cancers. Epidemiological studies showed that obesity might influence many cancers including OC. One of the key factors that may link obesity and OC is leptin (LEP), known as an adipokine with pleiotropic effects on body homeostasis. This study aims to investigate the expression pattern of LEP, assess the methylation profiles of LEP and their associations with clinicopathological features including survival outcomes of OC patients. The protein expression of LEP was evaluated in 208 samples using both tissue microarray and immunohistochemistry techniques. The methylation profiles of LEP were measured in 63 formalin-fixed, paraffin-embedded tumor tissues by quantitative polymerase chain reaction using a MethyLight assay. Our results showed a significant association of LEP protein overexpression with several clinicopathological variables, mainly tumor subtype, LVI, age of menarche, tumor size and stage (p < 0.04). Kaplan–Meier analysis (using low expression versus high expression as a discriminator) indicated that LEP protein overexpression is a powerful positive prognosticator of both OC recurrence (DFS) and disease-specific survival (DSS) in our OC cohort (log-rank p = 0.01 and p = 0.002, respectively). This implies that patients with high LEP expression profiles live longer with less recurrence rates. Methylation analysis results demonstrated a clear association between no/low LEP protein expression pattern (38%) and LEP promoter CpG island hypermethylation (43%). Results of this study suggest that LEP is a powerful prognosticator of OC recurrence and DSS. LEP expression in OC seems to be regulated by its promoter hypermethylation through gene partial/total silencing. Further multi-institutional studies using larger cohorts are required to demystify the intricate molecular functions of this leptin-driven effects in OC pathophysiology and to accurately assess its theranostic potential and validate its prognostic/predictive power in OC onset, progression towards more effective and personalized management of OC patients.

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Section: Discussionmentioning

confidence: 99%

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Assidi

Yahya

Al-Zahrani

et al. 2021

IJMS

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“…Many epidemiology studies have suggested a correlation of BC with leptin and APN (summarised in Table 1). In relation to APN, it has been mostly regarded that there is a higher correlation of BC with lower levels of APN [17], in which it is also associated with greater chance of recurrence [18,19] and a more aggressive phenotype [20][21][22], hence an inverse relationship of APN level with cancer development [23]. In a similar fashion, APN levels are often higher in non-cancerous tissues [24] and by that reasoning lower in cancerous tissues [25].…”

Section: Clinical Significance Of Leptin and Adiponectin In Breast Cancer (Bc)mentioning

confidence: 99%

Complex interaction of adipokines in breast cancer and anti-tumour immunity; a new paradigm for cancer treatment

Tan¹,

Xie²,

Sfakianakis³

2021

JCRCT

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Obesity and its related complications have been the pressing disease pandemic affecting the developed world. It is well-established that the direct consequence of obesity in the cardiovascular system resulting in many diseases. However, its implications in carcinogenesis, cancer treatment and one’s anti-tumour immunity are gradually unfolding. To understand how fat cells can affect these, one needs to explore how the fat cell affects epithelial and immune cells. To this end, we explore the way how the adipocytes, via its production of adipokines, influence these cells, resulting in early epithelial cell transformation into cancer cells and influencing anti-tumour immunity once the cancer is established. In order to simplify our discussion, we focus this review on breast cancer. We propose that to have an effective therapy for cancer treatment, we need to intervene at the adipokine interaction with epithelial cells, cancer cells, and immune cells. In this review we also decipher the potential therapeutic targets in controlling carcinogenesis and disease progression.

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“…Currently, numerous studies have confirmed that tumorigenesis, progression and prognosis are closely related to tumor tissue gene expression (Li et al, 2021b;Lin et al, 2017;Zhang et al, 2019). The genetic expression features of the tumor microenvironment (TME) play an important impact in predicting the clinical outcome of tumor treatment (Llanos et al, 2021;Yang et al, 2021). The TME is mainly composed of cells and extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

Prognostic tumor microenvironment gene and the relationship with immune infiltration characteristics in metastatic breast cancer

Yang¹,

LIU²,

ZHANG³

et al. 2022

Biocell

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The aim of this study was to reveal genes associated with breast cancer metastasis, to investigate their intrinsic relationship with immune cell infiltration in the tumor microenvironment, and to screen for prognostic biomarkers. Gene expression data of breast cancer patients and their metastases were downloaded from the GEO, TCGA database. R language package was used to screen for differentially expressed genes, enrichment analysis of genes, PPI network construction, and also to elucidate key genes for diagnostic and prognostic survival. Spearman's r correlation was used to analyze the correlation between key genes and infiltrating immune cells. We screened 25 hub genes, FN1, CLEC5A, ATP8B4, TLR7, LY86, PTGER3 and other genes were differentially expressed in cancer and paraneoplastic tissues.However, patients with higher expression of CD1C, IL-18 breast cancer had a better prognosis in the 10 years survival period, while patients with high expression of FN1, EIF4EBP1 tumors had a worse prognosis. In addition, TP53 and HIF1 genes are closely related to the signaling pathway of breast cancer metastasis. In this study, gene expression of ATP8B4 and CD1C were correlated with cancer tissue infiltration of CD8 + T lymphocytes, while GSE43816, GSE62327 and TCGA databases showed that CD8 + T lymphocytes were closely associated with breast cancer progression. Functional enrichment analysis of genes based on expression differences yielded key genes of prognostic value in the breast cancer microenvironment.

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Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features

Cited by 14 publications

References 35 publications

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Leptin Protein Expression and Promoter Methylation in Ovarian Cancer: A Strong Prognostic Value with Theranostic Promises

Complex interaction of adipokines in breast cancer and anti-tumour immunity; a new paradigm for cancer treatment

Prognostic tumor microenvironment gene and the relationship with immune infiltration characteristics in metastatic breast cancer

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