The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

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Identification of glycolysis related pathways in pancreatic adenocarcinoma and liver hepatocellular carcinoma based on TCGA and GEO datasets

Cancer Cell International ◽

10.1186/s12935-021-01809-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ji Li ◽

Chen Zhu ◽

Peipei Yue ◽

Tianyu Zheng ◽

Yan Li ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Energy Metabolism ◽

Pancreatic Adenocarcinoma ◽

Digestive System ◽

Prognostic Significance ◽

R Package ◽

The Cancer Genome Atlas ◽

System Structure ◽

Liver Hepatocellular Carcinoma

Abstract Background Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms. Methods Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently. Results High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop. Conclusions Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism–signaling target combined therapy.

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Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05186-y ◽

2021 ◽

Author(s):

Xi Li ◽

S. Ali Montazeri ◽

Ricardo Paz-Fumagalli ◽

Carlos A. Padula ◽

Weiping Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Significance ◽

Neutrophil To Lymphocyte Ratio ◽

Glass Microspheres ◽

Lymphocyte Ratio

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Hepatoblastoma: glutamine depletion hinders cell viability in the embryonal subtype but high GLUL expression is associated with better overall survival

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03713-4 ◽

2021 ◽

Author(s):

Andreas Schmidt ◽

Angela Armento ◽

Ovidio Bussolati ◽

Martina Chiu ◽

Verena Ellerkamp ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Growth Inhibition ◽

Cell Viability ◽

Cell Lines ◽

Prognostic Significance ◽

Asparagine Synthetase ◽

Inhibition Of Proliferation ◽

Its Gene ◽

Glutamine Synthesis

Abstract Purpose Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic factor and potential therapeutic target in adult hepatocellular carcinoma, we investigated the expression of its gene ASNS and of the gene GLUL, encoding for glutamine synthetase, in hepatoblastoma specimens and cell lines and investigated the correlation with overall survival. Methods We correlated GLUL and ASNS expression with overall survival using publicly available microarray and clinical data. We examined GLUL and ASNS expression by RT-qPCR and by Western blot analysis in the embryonal cell lines Huh-6 and HepT1, and in five hepatoblastoma specimens. In the same cell lines, we investigated the effects of glutamine depletion. Hepatoblastoma biopsies were examined for histology and CTNNB1 mutations. Results High GLUL expression was associated with a higher median survival time. Independent of mutations and histology, hepatoblastoma samples showed strong GLUL expression and glutamine synthesis. Glutamine depletion resulted in the inhibition of proliferation and of cell viability in both embryonal hepatoblastoma cell lines. ASNS expression did not correlate with overall survival. Conclusion Growth inhibition resulting from glutamine depletion, as described for the hepatoblastoma fetal subtype, is also detected in established embryonal hepatoblastoma cell lines carrying different mutations. At variance with adult hepatocellular carcinoma, in hepatoblastoma asparagine synthetase has no prognostic significance.

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A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-021-08351-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Liang Hong ◽

Yu Zhou ◽

Xiangbang Xie ◽

Wanrui Wu ◽

Changsheng Shi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Molecular Subtypes ◽

Prognostic Significance ◽

Predictive Performance ◽

Gene Signature ◽

The Cancer Genome Atlas ◽

Cumulative Distribution ◽

Gene Module ◽

Expression Levels

Abstract Background Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear. Methods Molecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature. Results We identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature. Conclusions Findings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.

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