Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide despite the availability of diverse treatment strategies. Much research progress has been made regarding immunotherapy but the effects remain unsatisfactory, highlighting the urgent need for novel immune-related therapy targets. In recent years, more and more studies have pointed out the associations between certain transmembrane (TMEM) family proteins and tumor progression, but the role of TMEM205 remains unclear. In this study, we analyzed the RNA-seq and clinical data of 371 patients from The Cancer Genome Atlas (TCGA) and found significant differential expression of TMEM205 between normal and tumor tissues (P < 0.001). Low TMEM205 expression was also found to be independently associated with poor overall survival (OS; p = 0.032) and poor disease-specific survival (DSS; p = 0.002) in multivariate Cox regression analyses. RNA-seq and clinical data from hepatocellular carcinoma patients in the International Cancer Genome Consortium (ICGC) also showed significant differential expression of TMEM205 (P < 0.001) and association between low TMEM205 expression and poor survival (P < 0.001). We also used the Estimate the Proportion of Immune and Cancer cells (EPIC) tool to estimate the proportions of various immune cells in the tumor tissues. A correlation analysis was conducted, and TMEM205 expression in tumor tissues was found to be significantly associated with the proportion of macrophages (Pearson r = 0.45, p < 0.0001). A negative correlation was found between TMEM205 expression and M2 macrophage markers (CD163, EGR2, and MS4A4A) and between TMEM205 expression and regulatory T cell (Treg) markers (CCR8, STAT5B, and IL2RA), while a positive correlation was found between TMEM205 expression and the proportion of CD8+ T cells (Pearson r = 0.26, p < 0.0001). In conclusion, TMEM205 might improve HCC patients’ prognosis by reducing the levels of immunosuppressive cells (M2 macrophages and Tregs) and facilitating the infiltration of cytotoxic T cells into the tumor microenvironment. Therefore, TMEM205 has potential as a prognostic biomarker and immunotherapy agent in combination therapy regimens for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, causing nearly 800,000 deaths every year (Ferlay et al, 2015)
We found significant difference in TMEM205 expression between normal tissue and tumor tissue (p < 0.001) and demonstrated that low TMEM205 expression was independently associated with poor overall survival (OS) (p = 0.032) and disease-specific survival (DSS) (p = 0.002) in HCC patients from the The Cancer Genome Atlas (TCGA) cohort
A significant differential expression of TMEM205 was observed (p < 0.001) and low TMEM205 expression still predicted poor survival (p < 0.001) in HCC patients from the International Cancer Genome Consortium (ICGC) cohort, which validated that TMEM205 expression was an independent prognostic factor in HCC
Summary
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, causing nearly 800,000 deaths every year (Ferlay et al, 2015). The limited clinical effect of immunotherapy (e.g., anti-PD-1) may be related to disturbances in the immunosuppressive cells (such as increased M2-like macrophage levels) in the TME, and there is an urgent need for a detailed understanding of the TAM-mediated inhibition of cytotoxic T cells (Noy and Pollard, 2014). Using RNA-seq data and clinical data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), this study explored whether TMEM205 is a prognostic marker in HCC patients and the associations between TMEM205 expression and the proportions of different types of immune cells in the TME.
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