Abstract
BackgroundBreast cancer (BC) is the most diagnosed cancer and the leading cause of global cancer incidence in 2020. It is quite known that highly invasive cancers have disrupted metabolism that leads to the creation of an acidic tumor microenvironment. Among the proton-sensing G protein-coupled receptors is GPR68. In this study, we aimed to explore the expression pattern of GPR68 in tissues from BC patients as well as different BC cell lines. Methods: In-silico tools were used to assess the expression of GPR68 in BC patients. The expression pattern was validated in fresh and paraffin-embedded sections of BC patients using qPCR and immunohistochemistry (IHC), respectively. Also, in-silico tools investigated GPR68 expression in different BC cell lines. Validation of GPR68 expression was performed using qPCR and immunofluorescence techniques in four different BC cell lines (MCF-7, MDA-MB-231, BT-549 and SkBr3). Results: GPR68 expression was found to be significantly increased in BC patients using the in-silico tools and validation using qPCR and IHC. Upon classification according to the molecular subtypes, the luminal subtype showed the highest GPR68 expression followed by triple-negative and Her2-enriched cells. However, upon validation in the recruited cohort, the triple-negative molecular subtype of BC patients showed the highest GPR68 expression. Also, in-silico and validation data revealed that the triple-negative breast cancer cell line MDA-MB-231 showed the highest expression of GPR68. Conclusion: Therefore, this study highlights the potential utilization of GPR68 as a possible diagnostic and/or prognostic marker in BC.
Highlights
According to the World Health Organization (WHO), breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of global cancer incidence in 2020, with an estimated 2.3 million new cases, representing 11.7% of all cancer cases
Breast cancer (BC) tumor tissue showed higher GPR68 expression compared to adjacent normal tissues (p=1.15e-17). This was further validated by UALCAN tool where a similar expression pattern was observed in BC patients (n=1097) that showed significantly higher GPR68 compared to normal breast tissues (n=114) with a p-value of 1.63e-12 (Figure 1D)
The effects of acidosis on cancer cells have been previously investigated in different tumors [3]
Summary
According to the World Health Organization (WHO), breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of global cancer incidence in 2020, with an estimated 2.3 million new cases, representing 11.7% of all cancer cases. It is quite known that highly malignant and invasive cancers have disrupted metabolism and an elevated glycolytic activity. This creates an acidic milieu, known as the Warburg effect, which is an important hallmark of the tumor microenvironment (TME) [2]. Such an environment regulates proliferation, apoptosis, and metastasis of cancer cells as well as modulate inflammation, anti-tumor immunity, and angiogenesis [3–5]. It is quite known that highly invasive cancers have disrupted metabolism that leads to the creation of an acidic tumor microenvironment. In-silico and validation data revealed that the triple-negative breast cancer cell line MDA-MB-231 showed the highest expression of GPR68. Conclusion: this study highlights the potential utilization of GPR68 as a possible diagnostic and/or prognostic marker in BC
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