TMED2/9/10 Serve as Biomarkers for Poor Prognosis in Head and Neck Squamous Carcinoma

Abstract

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies’ progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated.Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC.Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC.Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

TMED family genes and their roles in human diseases

“…TMED2/9/10 and its co-expressed genes appear to be involved in tumor biological processes such as intracellular transferase complex, protein transport, focal adhesion, and intracellular protein processing, which contribute to malignant behavior, according to analyses from Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). These findings imply that TMED2/9/10 and related genes may affect HNSC's prognosis as a whole 49 . Genes like X-box binding protein 1 (XBP1) and TMED7 have been identified in transcription factor-gene and protein-protein interaction (PPI) networks as potential HNSC modifiers that may cooperate with TMED2/9/10.…”

BCAP29/31 as a Poor Prognostic Biomarker for Head and Neck Squamous Carcinoma: Impacting the TGFβ1/Smad- EMT Pathway

“…The functions of the genes that appear to be common in the BCAP29/31 reciprocal network have also been explored to some extent. Among them, STT3A and STT3B may induce endoplasmic reticulum stress-dependent apoptosis in breast cancer [51], and TMED10 has been shown to act as a biomarker of poor prognosis in HNSC [52], these results suggest that in HNSC, BCAP29/31 may still play a synergistic role at the level of endoplasmic reticulum output and quality control, and have a prognostic situation.…”

Integrative Multi-Omics Analysis Identifies Transmembrane p24 Trafficking Protein 1 (TMED1) as a Potential Prognostic Marker in Colorectal Cancer

“…Additionally, some TMED proteins have been shown to regulate signaling pathways that promote tumor growth and survival, such as the Wnt signaling pathway and the PI3K/AKT signaling pathway [21,54]. TMED1 belongs to the TMED protein family and is overexpressed in various cancers [11,18]. However, the biological behavior of TMED1 in malignant tumors has yet to be fully elucidated, especially in CRC.…”

“…Furthermore, most members of this family have been reported to be associated with poor prognosis [16,17]. The expression of TMED2 is elevated in head and neck squamous carcinoma and breast cancer and acts as an unfavorable prognostic biomarker [18,19]. TMED3 is highly expressed in malignant melanoma and lung squamous cell carcinoma, which is important in advancing cancer [20,21].…”

“…TMED9 promotes colon cancer metastases and relates to vascular invasion and poor prognosis in hepatocellular carcinoma [23,24]. TMED1 is highly expressed in multiple tumor tissues [18], but its prognostic significance in malignant tumors has yet to be clarified, especially in CRC.…”