Expression and prognostic potential of TMEM204: a pan-cancer analysis

Abstract

TMEM204 (Transmembrane Protein 204) is a member of the TMEM family that regulates cell function and angiogenesis. Previous studies showed that TMEM204 is related to pancreatic cancer, but its roles in other cancers remain unknown. To reveal this relationship, we conducted a pan-cancer analysis by several online databases. The expression of TMEM204 was analyzed by Oncomine and Tumor Immune Estimation Resource2.0 (TIMER2.0). The prognostic potential of TMEM204 was evaluated by the GEPIA2, UALCAN, and Oncolnc. The methylation level of gene expression was analyzed by UALCAN, and the relationship between cancer and immune invasion was displayed by TIMER2.0. The Protein-Protein Interactions Network and functional analysis of TMEM204 and its related genes were conducted by STRING and Webgestalt. We found that TMEM204 expression was up-regulated and correlated with prognosis in multiple cancers. In liver hepatocellular carcinoma (LIHC), high TMEM204 expression was associated with a good prognosis, and with high infiltrating levels of CD8⁺ T and CD4⁺ T cells, macrophages, neutrophils, and myeloid dendritic cells. In addition, the methylation level in LIHC was higher than in normal tissues. p53 signaling pathway and Fanconi anemia pathway were implicated by KEGG pathway analysis. These results indicate that TMEM204 is associated with the prognosis, methylation, and immune invasion of cancers, especially LIHC. TMEM204 may act as a prognostic marker of LIHC and its role in other cancers should be studied.

Keywords: Expression; TMEM204; methylation; pan-cancer analysis; prognostic biomarker.

Figure 1

TMEM204 expression in cancers. A. TMEM204 data showing an increase or decrease in various cancers compared to normal tissues in the Oncomine database. B. TMEM204 expression profiles in all tumor samples and matched normal tissues were detected by TIMER2.0. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Figure 2

Survival curves of TMEM204 in different cancers obtained through GEPIA2, UALCAN, and Oncolnc databases. GEPIA2: (A-F), UALCAN: (G-J), Oncolnc: (K-N). (A) OS survival curve of BLCA (n=402). (B, E) OS and DFS survival curves of KIRC (n=516). (C, F) OS and DFS survival curves of LIHC (n=364). (D) OS survival curves of LUSC (n=482). (G-J) Survival curves of COAD, KIRC, KIRP, and LIHC in UALCAN. (K-N) Survival curve of KIRC, LIHC, LUSC, and STAD in Oncolnc.

Figure 3

Box plot of TMEM204 expression levels in tumors based on UALCAN and Oncomine database. A. The box plot shows the relative expression of TMEM204 in normal and LIHC tissue. B. The box plot shows the relative expression of TMEM204 in LIHC based on histologic subtype. C. The box plot shows the relative expression of TMEM204 in LIHC based on gender. D. The box plot shows the relative expression of TMEM204 in the liver and hepatocellular carcinoma. ***P < 0.001.

Figure 4

Promoter methylation level of TMEM204 in LIHC through UALCAN. *P < 0.05.

Figure 5

Gene alterations in TMEM204 in LIHC tissue. A. Showing mutations in TMEM204 in LIHC. B. Details of all mutations in LIHC. C. Frequency of genetic alterations in LIHC. D. Disease-specific survival curve, disease-free survival curve, progression-free survival curve, and overall survival curve of gene alterations in LIHC.

Figure 6

Correlation of TMEM204 expression with immune infiltration level in LIHC.

Figure 7

PPI network and functional enrichment of TMEM204. A. PPI network of TMEM204-related genes was constructed in STRING. B. Biological processes, cell composition, and molecular function map related to TMEM204. C. KEGG pathway figure of TMEM204.