Abstract
Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC. Patient data were extracted from cohorts in the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Differential expression of TMED3 was observed between the low stage (Stage I and II) and high stage (Stage III and IV) patients in the TCGA and ICGC cohorts and between the low grade (Grade I and II) and high grade (Grade III and IV) patients in the TCGA cohort. Further, we evaluated TMED3 expression as a prognostic gene using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno’s C-index, and the AUC of the receiver operating characteristics at 5 years. The Kaplan-Meier analysis revealed that TMED3 overexpression was associated with poor prognosis for ccRCC patients. Analysis of the C-indices and area under the receiver operating characteristic curve further supported this. Multivariate analysis confirmed the prognostic significance of TMED3 expression levels (P = 0.005 and 0.006 for TCGA and ICGC, respectively). Taken together, these findings demonstrate that TMED3 is a potential prognostic factor for ccRCC.
Highlights
The transmembrane emp24 domain (TMED) protein family is involved in the vesicular trafficking of proteins and innate immune signaling (Strating and Martens, 2009; Zheng et al, 2016)
The expression of TMED3 was compared between low (Stage I and II) and high stage (Stage III and IV) clear cell renal cell carcinoma (ccRCC) patients in the the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, and between low (Grade I and II) and high grade (Grade III and IV) ccRCC patients from the TCGA cohort
We confirmed that the TMED3 gene fulfills a sufficient role as a universal prognostic marker for ccRCC
Summary
The transmembrane emp domain (TMED) protein family is involved in the vesicular trafficking of proteins and innate immune signaling (Strating and Martens, 2009; Zheng et al, 2016). TMED proteins contain a Golgi dynamics domain and function in Golgi dynamics and intracellular protein trafficking Recent studies have implicated TMED7 in the regulation of TLR4 signaling (Palsson-McDermott et al, 2009; Doyle et al, 2012; Liaunardy-Jopeace et al, 2014), and TMED1 is involved in the ST2L-IL33 axis (Connolly et al, 2013). A recent study showed that TMED3 overexpression was significantly correlated with an aggressive phenotype of HCC and poor prognosis (Zheng et al, 2016). The clinical significance of TMED3 and its role in other malignancies are unknown
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