scholarly journals TMEM205 Is an Independent Prognostic Factor and Is Associated With Immune Cell Infiltrates in Hepatocellular Carcinoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Jiawei Rao ◽  
Xukun Wu ◽  
Xiaozhuan Zhou ◽  
Ronghai Deng ◽  
Yi Ma
2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Lu ◽  
Shenglan Cai ◽  
Xiaozhen Peng ◽  
Ruochan Cheng ◽  
Yiya Zhang

The Na+/K+-ATPase (NKA), has been proposed as a signal transducer involving various pathobiological processes, including tumorigenesis. However, the clinical relevance of NKA in hepatocellular carcinoma (HCC) has not been well studied. This study revealed the upregulation of mRNA of ATP1A1, ATP1B1, and ATP1B3 in HCC using TCGA, ICGC, and GEO database. Subsequently, ATP1B3 was demonstrated as an independent prognostic factor of overall survival (OS) of HCC. To investigate the potential mechanisms of ATP1B3 in HCC, we analyzed the co-expression network using LinkedOmics and found that ATP1B3 co-expressed genes were associated with immune-related biological processes. Furthermore, we found that ATP1B3 was correlated immune cell infiltration and immune-related cytokines expression in HCC. The protein level of ATP1B3 was also validated as a prognostic significance and was correlated with immune infiltration in HCC using two proteomics datasets. Finally, functional analysis revealed that ATP1B3 was increased in HCC cells and tissues, silenced ATP1B3 repressed HCC cell proliferation, migration, and promoted HCC cell apoptosis and epithelial to mesenchymal transition (EMT). In conclusion, these findings proved that ATP1B3 could be an oncogene and it was demonstrated as an independent prognostic factor and correlated with immune infiltration in HCC, revealing new insights into the prognostic role and potential immune regulation of ATP1B3 in HCC progression and provide a novel possible therapeutic strategy for HCC.


Author(s):  
Xiao-Wei Fu ◽  
Chun-Qing Song

Background: Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and accounts for the fourth common cause of cancer-related deaths. Recently, pyroptosis has been revealed to be involved in the progression of multiple cancers. However, the role of pyroptosis in the HCC prognosis remains elusive.Methods: The clinical information and RNA-seq data of the HCC patients were collected from the TCGA-LIHC datasets, and the differential pyroptosis-related genes (PRG) were firstly explored. The univariate Cox regression and consensus clustering were applied to recognize the HCC subtypes. The prognostic PRGs were then submitted to the LASSO regression analysis to build a prognostic model in the TCGA training cohort. We further evaluated the predictive model in the TCGA test cohort and ICGC validation cohort (LIRI-JP). The accuracy of prediction was validated using the Kaplan—Meier (K-M) and receiver operating characteristic (ROC) analyses. The single-sample gene set enrichment analysis (ssGSEA) was used to determine the differential immune cell infiltrations and related pathways. Finally, the expression of the prognostic genes was validated by qRT-PCR in vivo and in vitro.Results: We identified a total of 26 differential PRGs, among which three PRGs comprising GSDME, GPX4, and SCAF11 were subsequently chosen for constructing a prognostic model. This model significantly distinguished the HCC patients with different survival years in the TCGA training, test, and ICGC validation cohorts. The risk score of this model was confirmed as an independent prognostic factor. A nomogram was generated indicating the survival years for each HCC patient. The ssGSEA demonstrated several tumor-infiltrating immune cells to be remarkably associated with the risk scores. The qRT-PCR results also showed the apparent dysregulation of PRGs in HCC. Finally, the drug sensitivity was analyzed, indicating that Lenvatinib might impact the progression of HCC via targeting GSDME, which was also validated in human Huh7 cells.Conclusion: The PRG signature comprised of GSDME, GPX4, and SCAF11 can serve as an independent prognostic factor for HCC patients, which would provide further evidence for more clinical and functional studies.


BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Akihiro Tanemura ◽  
Shugo Mizuno ◽  
Aoi Hayasaki ◽  
Kazuyuki Gyoten ◽  
Takehiro Fujii ◽  
...  

Abstract Background Several inflammation-based scores are used to assess the surgical outcomes of hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the prognostic value of the prognostic nutritional index (PNI) in HCC patients who underwent hepatectomy with special attention to preoperative liver functional reserve. Methods Preoperative demographic and tumor-related factors were analyzed in 189 patients with HCC undergoing initial hepatectomy from August 2005 to May 2016 to identify significant prognostic factors. Results Multivariate analysis for overall survival (OS) revealed that female sex (p = 0.005), tumor size (p < 0.001) and PNI (p = 0.001) were independent prognostic factors. Compared to the High PNI group (PNI ≥ 37, n = 172), the Low PNI group (PNI < 37, n = 17) had impaired liver function and significantly poorer OS (13% vs. 67% in 5-year OS, p = 0.001) and recurrence-free survival (RFS) (8 vs. 25 months in median PFS time, p = 0.002). In the subgroup of patients with a preserved liver function of LHL15 ≥ 0.9, PNI was also independent prognostic factor, and OS (21% vs. 70% in 5-year OS, p = 0.008) and RFS (8 vs. 28 months in median PFS time, p = 0.018) were significantly poorer in the Low PNI group than the High PNI group. Conclusions PNI was an independent prognostic factor for HCC patients who underwent hepatectomy. Patients with PNI lower than 37 were at high risk for early recurrence and poor patient survival, especially in the patients with preserved liver function of LHL ≥ 0.9.


2004 ◽  
Vol 41 (1) ◽  
pp. 104-111 ◽  
Author(s):  
Tsutomu Fujii ◽  
Katsumi Koshikawa ◽  
Shuji Nomoto ◽  
Osamu Okochi ◽  
Tetsuya Kaneko ◽  
...  

2015 ◽  
Vol 19 (4) ◽  
pp. 167 ◽  
Author(s):  
Ye-Rang Jang ◽  
Kwang-Woong Lee ◽  
Hyeyoung Kim ◽  
Jeong-Moo Lee ◽  
Nam-Joon Yi ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Binsheng Fu ◽  
Wei Meng ◽  
Xiancheng Zeng ◽  
Hui Zhao ◽  
Wei Liu ◽  
...  

Thioredoxin reductase 1 (TXNRD1) which is a selenocysteine-containing protein is overexpressed in many malignancies. Its role in the hepatocellular carcinoma (HCC) prognosis has not been investigated. In this study, we investigated whether TXNRD1 functions as an independent prognostic factor for HCC patients. We found TXNRD1 was overexpressed in HCC tissues and cells, immunohistochemical analysis suggested TXNRD1 was elevated in 57 of 120 (47.5%) clinical samples, and its level was increased with the increasing clinical stage. In addition, TXNRD1 expression was positively correlated with clinical stage (p=3.5e-5), N classification (p=4.4e-4), and M classification (p=0.037) of HCC patients. Kaplan-Meier analysis revealed that patients with high TXNRD1 expression had significantly shorter survival time than patients with low TXNRD1 expression. Multivariate analysis found TXNRD1 was an independent prognostic factor for HCC patients. In conclusion, our data suggested that TXNRD1 was a biomarker for the prognosis of patients with HCC.


2021 ◽  
Vol 12 (13) ◽  
pp. 4039-4048
Author(s):  
Fahui Liu ◽  
Wanyun Hou ◽  
Jiadong Liang ◽  
Lilan Zhu ◽  
Chunying Luo

2021 ◽  
pp. 1-12
Author(s):  
Mingxin Cui ◽  
Fengzhi Qu ◽  
Libing Wang ◽  
Xiaogang Liu ◽  
Jingkun Yu ◽  
...  

Hepatocellular carcinoma (HCC) is a cancer with relatively high mortality, yet little attention has been devoted for related prognostic biomarkers. This study analyzed differential expression of m5C RNA methyltransferase-related genes in normal samples and tumors samples in TCGA-LIHC using Wilcoxon test. K-means consensus clustering analysis was implemented to subdivide samples. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. KEGG pathway enrichment analysis was performed on the screened independent prognostic factor using GSEA tools. qPCR was conducted to test mRNA expression of key m5C RNA methyltransferase-related genes in tissues and cells. There were 7 m5C RNA methyltransferase-related genes (NOP2, NSUN4, etc.) differentially expressed in HCC tumor tissues. HCC samples were classified into 3 subgroups through clustering analysis according to the expression mode of m5C RNA methyltransferase-related genes. It was also discovered that patients in different subgroups presented significant differences in survival rate and distribution of grade. Additionally, NOP2, NSUN4 and NSUN5 expression notable varied in different grades. Through regression analyses combined with various clinical pathological factors, it was displayed that NSUN4 could work as an independent prognostic factor. KEGG analysis showed that NSUN4 mainly enriched in signaling pathways involved in ADHERENS JUNCTION, RNA DEGRADATION, MTOR SIGNALING PATHWAY, COMPLEMENT and COAGULATION CASCADES. As examined by qPCR, NSUN4 was conspicuously upregulated in HCC patient’s tissues and cells. Altogether, our study preliminarily developed a novel biomarker that could be independently used in prognosis of HCC, which may provide a new direction for the study of related molecular mechanism or treatment regimen.


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