High expression of transmembrane P24 trafficking protein 9 predicts poor prognosis in breast carcinoma

ABSTRACT

Over the years, molecular subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) status have been observed to effectively guide decision-making for the optimal treatment of patients with breast carcinoma (BRCA). However, despite this progress, there are still more than 41,000 BRCA-related fatalities each year in the United States. Moreover, effective drug targets for triple-negative breast carcinoma (TNBC) are still lacking. Given its high mortality rate, it is necessary to investigate more biomarkers with prognostic and pathological relevance in BRCA. In our study, we examined the expression patterns and prognostic implications of transmembrane P24 trafficking protein 9 (TMED9) in BRCA using multiple public cohorts and BRCA specimens collected from Shanghai General Hospital. In addition to this, in vitro experiments were also performed to evaluate the effects of TMED9 expression in BRCA cell proliferation and migration. Our results have demonstrated that a high expression of TMED9 promoted BRCA cell proliferation and migration and predicted poor prognosis in patients with BRCA. In conclusion, TMED9 is a potential prognostic indicator and a possible drug target of BRCA.

KEYWORDS:

• TMED9
• breast carcinoma
• biomarker
• prognosis
• bioinformatics

Research highlights

1. TMED9 expression was higher in BRCA samples than in normal breast samples.

2. High TMED9 expression predicted poor prognosis in patients with BRCA.

3. TMED9 knockdown suppressed MDA-MB-231 and BT549 cells proliferation and migration in vitro.

Abbreviations

TMED9, transmembrane P24 trafficking protein 9; TCGA, the cancer genome atlas; GEO, Gene Expression Omnibus; BRCA, breast carcinoma; ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor-2; TNBC, triple negative breast carcinoma; IHC, immunohistochemistry; GEPIA, Gene Expression Profiling Interactive Analysis; HPA, human protein atlas; CPTAC, Clinical Proteomic Tumor Analysis Consortium; PPI, protein-protein interaction; GO, gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; FDR, false discovery rate; GSCA, Gene Set Cancer Aanlysis; GDSC, Genomics of Drug Sensitivity in Cancer; CTRP, Genomics of Therapeutics Response Portal; DMEM, Dulbecco’s modified eagle medium; COPE, COPI coat complex subunit epsilon; TMED1, transmembrane p24 trafficking protein 1; BNIP1, BCL2 interacting protein 1; PPIB, peptidylprolyl isomerase B; P4HB, prolyl 4-hydroxylase subunit beta; MYDGF, myeloid derived growth factor; B4GALT7, beta-1,4-galactosyltransferase 7.

Acknowledgements

The results of this study were based on the data obtained in these cohorts: TCGA-BRCA, GSE15852, GSE24124, GSE3344, and GSE53752. Online tools (GEPIA 2.0, HPA, UALCAN, PrognoScan, GSCA, and DepMap Portal) were used to simplify the methods of data analysis. We thank the contributors of data and tools in our study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.