Abstract

As recently reported by The International Agency for Research on Cancer (IARC), breast cancer has the highest incidence of all cancers in 2020. Many studies have revealed that golgi apparatus is closely associated with the development of breast cancer. However, the role of golgi apparatus in immune microenvironment is still not clear. In this study, using RNA-Seq datasets of breast cancer patients from the public database (n = 1080), we revealed that GOLT1B, encoding a golgi vesicle transporter protein, was significantly higher expressed in human breast cancer tissues versus normal tissues. Besides, we verified GOLT1B expression in five breast cancer cell line using our original data and found GOLT1B was significantly up-regulated in MDA-MB-231, MCF-7, SKBR3. Subsequently, we identified GOLT1B as a potential independent prognostic factor for breast cancer. After a multi-omics analysis, we uncovered that the higher expression of GOLT1B in breast cancer tissues versus normal tissues might be due to the amplification of GOLT1B and altered phosphorylation of its potential transcriptional factors, including JUN and SIN3A. Subsequently, we discovered that GOLT1B potentially regulated the immune microenvironment basing on the finding that its expression was closely related to the tumor microenvironment score and infiltration of immune cells. Moreover, we revealed that GOLT1B might affect the overall survival rates of breast cancer through regulating the immune cell infiltration. Finally, we disclosed the potential pathways involved in the functions of GOLT1B in breast cancer, including metabolism and ECM-receptor interaction pathways. To sum up, we identified GOLT1B as a potential prognostic gene for breast cancer and disclosed its role in regulating the immune microenvironment.

Highlights

  • The International Agency for Research on Cancer (IARC) has released “the latest data on the global burden of cancer in 2020” [1] showing that the incidence of breast cancer has replaced lung cancer in the first place in the world, accounting for 11.7% of new cancer cases

  • The results showed that GOLT1B was up-regulated in 25 types of tumors, such as breast invasive carcinoma (BRCA), adrenal cortical carcinoma (ACC), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), clear cell carcinoma of the kidney (KIRC), squamous cell carcinoma of the head and neck (HNSC), liver hepatocellular carcinoma (LIHC), acute myeloid leukemia (LAML)

  • We investigated the expression of GOLT1B in BRCA tissues and para-cancerous tissues using the datasets from the Cancer Genome Atlas (TCGA), and the results showed that GOLT1B mRNA was significantly elevated in BRCA tissues (Figure 1C)

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Summary

Introduction

The International Agency for Research on Cancer (IARC) has released “the latest data on the global burden of cancer in 2020” [1] showing that the incidence of breast cancer has replaced lung cancer in the first place in the world, accounting for 11.7% of new cancer cases. With the progress of diagnosis and treatment, the 5-year survival rate of breast cancer has been improved, the mortality rate of patients with advanced breast cancer still reach to more than 70% [2]. Distinguishing high-risk patients by prognostic biomarkers can frequently lead to an appropriate individualized treatment and reduce the mortality. The effects of immunotherapy in breast cancer are not satisfactory. There is a necessary to further explore the mechanism underlying the development of breast cancer and search for key regulatory genes of immune microenvironment. Golgi apparatus is closely related to innate immune signal transduction and subsequent effect response [6]. The essential role of the golgi apparatus in carcinogenesis has been well characterized, its functions in tumor immune microenvironment are still unclear

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