Prognostic Marker For Hepatocellular Carcinoma Research Articles

ADH4—a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications

ObjectiveThis study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment.MethodsHCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues.ResultsADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy.ConclusionThis study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

A comprehensive analysis of GAS2 family members identifies that GAS2L1 is a novel biomarker and promotes the proliferation of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a high incidence and mortality. Members of the growth-arresting-specific 2 (GAS2) family are involved in various biological processes in human malignancies. To date, there is only a limited amount of information available about the expression profile and clinical importance of GAS2 family in HCC. In this study, we found that GAS2L1 and GAS2L3 were distinctly upregulated in HCC specimens compared to non-tumor specimens. Pan-cancer assays indicated that GAS2L1 and GAS2L3 were highly expressed in most cancers. The Pearson’s correlation revealed that the expressions of GAS2, GAS2L1 and GAS2L2 were negatively associated with methylation levels. Survival assays indicated that GAS2L1 and GAS2L3 were independent prognostic factors for HCC patients. Immune cell infiltration analysis revealed that GAS2, GAS2L1 and GAS2L3 were associated with several immune cells. Finally, we confirmed that GAS2L1 was highly expressed in HCC cells and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings suggested the expression patterns and prognostic values of GAS2 members in HCC, providing insights for further study of the GAS2 family as sensitive diagnostic and prognostic markers for HCC.

Apolipoprotein H-based prognostic risk correlates with liver lipid metabolism disorder in patients with HBV-related hepatocellular carcinoma

Background/Aim: Chronic hepatitis B patients often develop concomitant fatty liver disease, which is associated with increased risk of liver cirrhosis and hepatocarcinoma. Our previous studies have shown that apolipoprotein H (APOH) levels are gradually decreased in patients with chronic HBV infection at different stages of disease progression, and APOH deficiency disrupted hepatic lipid metabolism and caused fatty liver. We focus on the relationship between APOH and hepatocellular carcinoma (HCC) in the context of chronic HBV infection. Methods and resultsAPOH was downregulated at the transcriptional level in HBV-related HCC patients from open-source human liver transcriptome databases, and relatively high expression of APOH might be a favourable prognostic marker in HCC. APOH downregulation was positively associated with tumour grade and HCC subtypes. The analysis result of CHCC-HBV database showed that APOH-associated differential expression genes (DEGs) enriched in lipid metabolic pathways and downregulated APOH correlated with macrophage, neutrophil and CD8 T cell infiltration levels. Next, in vitro experiments were performed and APOH gene was silenced in HepG2.2.15 cells, an HBV producing human HCC cells. Further transcriptomic assay and analysis revealed the DEGs were enriched in cholesterol metabolism. The subsequent RT-qPCR experiments identified that CYP7A1 expression was higher upregulated in APOH silencing HepG2.2.15 cells than vehicle control cells (p < 0.05). Finally, demographic data of patients with HBV-related HCC were enrolled, and serum APOH levels were analysed using ELISA. Serum APOH levels were significantly lower in patients with HCC than in healthy controls (p < 0.05), and positively correlated with triglyceride level in healthy controls (p < 0.05). In HBV-HCC patients, serum APOH levels were positively correlated with albumin levels and negatively correlated with alkaline phosphatase (ALP), total bilirubin, and INR levels (p < 0.05). ConclusionAPOH downregulation disrupted liver lipid metabolism to potentially affect the overall survival in patients with HBV-related HCC.

Global contextual representation via graph-transformer fusion for hepatocellular carcinoma prognosis in whole-slide images

Current methods of digital pathological images typically employ small image patches to learn local representative features to overcome the issues of computationally heavy and memory limitations. However, the global contextual features are not fully considered in whole-slide images (WSIs). Here, we designed a hybrid model that utilizes Graph Neural Network (GNN) module and Transformer module for the representation of global contextual features, called TransGNN. GNN module built a WSI-Graph for the foreground area of a WSI for explicitly capturing structural features, and the Transformer module through the self-attention mechanism implicitly learned the global context information. The prognostic markers of hepatocellular carcinoma (HCC) prognostic biomarkers were used to illustrate the importance of global contextual information in cancer histopathological analysis. Our model was validated using 362 WSIs from 355 HCC patients diagnosed from The Cancer Genome Atlas (TCGA). It showed impressive performance with a Concordance Index (C-Index) of 0.7308 (95% Confidence Interval (CI): (0.6283–0.8333)) for overall survival prediction and achieved the best performance among all models. Additionally, our model achieved an area under curve of 0.7904, 0.8087, and 0.8004 for 1-year, 3-year, and 5-year survival predictions, respectively. We further verified the superior performance of our model in HCC risk stratification and its clinical value through Kaplan–Meier curve and univariate and multivariate COX regression analysis. Our research demonstrated that TransGNN effectively utilized the context information of WSIs and contributed to the clinical prognostic evaluation of HCC.

Impact of Thrombocytopenia on Survival in Patients with Hepatocellular Carcinoma: Updated Meta-Analysis and Systematic Review.

Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06-1.25; random-effect HR = 1.30, 95% CI: 1.05-1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary.

A Meta-Analysis of MiRNA-497 and Prognosis of Hepatocellular Carcinoma.

Recently, microRNA-497 (miR-497) has been reported as a prognostic marker for hepatocellular carcinoma (HCC). However, there is no systematic study summarizing these data. Herein, we elucidated the prognostic role of miR497 in HCC by using meta-analysis. We systematically searched Embase, PubMed, Web of Science, and, China National Knowledge Infrastructure for relevant studies. The two researchers conducted data extraction and quality evaluation independently. We used hazard ratios (HRs), odds ratios (ORs), and their 95% confidence interval (95% CI) to evaluate the relationship between miR-497 expression level and HCC prognosis. A total of 6 studies involving 457 participants were included in this meta-analysis. There was a significant association between the lower level of miR-497 expression and the shorter overall survival (HR = 2.17, 95% CI: 1.67-2.84, P < 0.001). Meanwhile, patients with low miR-497 expression were more prone to vascular infiltration (OR = 2.73, 95%: 1.79-4.17, P < 0.001). However, the lower expression level of miR-497 had no significant correlation with TNM (tumor-node-metastasis) stage (OR = 1.47, 95% CI: 0.17-12.49, P=0.47). MiR-497 might serve as a prognostic biomarker in HCC, but more clinical studies are needed to confirm this view.

Clinical Significance and Functional Insights of Tesmin in Hepatocellular Carcinoma.

Tesmin, a 60 kDa protein encoded by the metallothionein-like 5 (MTL5) gene, plays a vital role in spermatogenesis and oogenesis. Recent research has unveiled its potential involvement in malignancies, although its impact on HCC remains poorly understood. In this study, we sought to elucidate the clinical significance of tesmin in HCC patients. We investigated the relationship between tesmin expression and the prognosis of individuals with hepatocellular carcinoma (HCC), as well as its potential role in tumor proliferation and invasion. Immunohistochemistry (IHC) was employed to assess the expression of tesmin in HCC tissues. Chi-square tests were conducted to analyze the correlation between tesmin expression and various clinicopathological features among HCC patients. For survival analysis, we employed the Kaplan-Meier method and conducted Cox regression analyses. To investigate the functional role of tesmin, we utilized shRNA constructs for transfection-mediated knockdown. Proliferation was assessed using the CCK-8 assay, and invasive capability was determined through Matrigel Transwell assays. IHC results indicated that tesmin expression was prominently observed in cancerous tissue. Notably, we observed a significant association between tesmin expression and tumor stage and invasion in HCC patients from both our medical center and TCGA dataset. Survival analysis further revealed that tesmin expression emerged as an independent prognostic factor for overall survival among individuals with HCC. Furthermore, cellular experiments demonstrated that knockdown of tesmin led to decreased proliferation and invasion of HCC cells. Our findings suggest that tesmin may serve as a novel prognostic marker for HCC, highlighting its potential as a target for further research into HCC treatment. Additionally, the functional experiments support the notion that tesmin may participate in promoting the proliferation and invasion of HCC cells, warranting further investigations into its mechanistic involvement in HCC progression.

CDK4 as a Prognostic Marker of Hepatocellular Carcinoma and CDK4 Inhibitors as Potential Therapeutics.

The proteins CDK4 and CDK6, which are extremely homologous, control cell cycle entry. For the treatment of breast tumors that include hormone receptors, CDK4 and CDK6 inhibitors have been authorized. The link between CDK4 and liver hepatocellular carcinoma (LIHC), however, has not yet been established. The study aimed to explore the link between CDK4 and LIHC and the effect of CDK4 inhibitors on LIHC. In this study, we have evaluated CDK4's prognostic relevance in LIHC using data from The Cancer Genome Atlas (TCGA). The relationship between clinical-pathologic features and CDK4 expression has been evaluated using the Kruskal-Wallis test, the Wilcoxon signed-rank test, and logistic regression. We have analyzed CDK4 and factors related to the prognosis of HCC using the Kaplan-Meier technique and multivariate Cox regression. Gene set enrichment analysis (GSEA) identified CDK4-related critical pathways. To investigate the connections between CDK4 and cancer immune infiltrates, TCGA data were employed in single-sample gene set enrichment analysis (ssGSEA). For functional validation, CDK4 was chosen since it can be inhibited by recognized CDK4/ 6-inhibitors (e.g., abemaciclib). Poorer overall and disease-specific outcomes were linked to high CDK4 expression in HCC patients. GSEA suggested that CDK4 and immune response are closely connected. The amount of Th2 cells infiltrating was positively correlated with CDK4 expression, while the amount of cytotoxic cells infiltrating was negatively correlated, according to ssGSEA. Both in vitro and in vivo, the anti-tumor efficacy of CDK4 inhibitor has been found to be superior to that of sorafenib. This study suggests a relationship between CDK4 and immune infiltration and prognosis in HCC. Additionally, a CDK4 inhibitor may have anti-tumor properties against hepatocellular cancer.

CMTM6 promotes hepatocellular carcinoma progression through stabilizing β-catenin

CMTM6, a regulator of PD-L1 stability, has been implicated in the development of various cancers. However, the expression and role of CMTM6 in hepatocellular carcinoma (HCC) remains controversial. Our study revealed a negative correlation between CMTM6 expression and HCC prognosis through bioinformatics analysis and immunofluorescence staining. CMTM6 expression was also positively associated with alpha-fetoprotein (AFP) levels, supporting its potential as a prognostic marker for HCC. Using Cmtm6 knockout mice, we found that Cmtm6 deficiency inhibited HCC formation and cell proliferation in primary liver cancer models induced by DEN and DEN/CCl4. In HCC cell lines, CMTM6 promoted cell proliferation and interacted with β-catenin, stabilizing it by preventing ubiquitination. In conclusion, our study suggested that CMTM6 upregulation promotes HCC cell proliferation through the β-catenin pathway, making it a potential therapeutic target for HCC treatment.

Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma

Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma

CCDC167 promotes hepatocellular carcinoma cell proliferation and is associated with the immune microenvironment of hepatocellular carcinoma

Coiled-coil domain-containing (CCDC)family proteins play an important role in tumour progression, however, the role of CCDC167 in hepatocellular carcinoma remains unclear. To investigate the role of coiled-coil structural domain 167 (CCDC167) in hepatocellular carcinoma progression, we downloaded three hepatocellular carcinoma datasets (TCGA-LIHC, ICGC-LIRI and GSE76427) and analysed the mechanisms by which CCDC167 regulates hepatocellular carcinoma progression using MetaScape, CPTAC, HPA, TISCH and TISIDB.“ pRRophetic” package predicted the chemotherapeutic agents associated with CCDC167. The results showed that CCDC167 was highly expressed in hepatocellular carcinoma tissues and was associated with poor prognosis in patients with hepatocellular carcinoma. Knockdown of CCDC167 inhibits the proliferative capacity of hepatocellular carcinoma cells. CCDC167 was involved in the regulation of cell cycle, DNA replication and oxidative phosphorylation. Hepatocellular carcinoma samples with high expression of CCDC167 showed higher immune scores and C4 (lymphocyte depleted) subtypes. CCDC167 was associated with a variety of immune molecules (CD274, IL6R, and KDR), not only that, but CCDC167 was positively correlated with Treg infiltration and negatively correlated with T cells CD4 memory resting. High expression of CCDC167 increased immune escape in hepatocellular carcinoma patients. CCDC167 was associated with sensitivity to cisplatin in hepatocellular carcinoma patients. CCDC167 promoted the proliferative capacity of hepatocellular carcinoma cells. Our study suggests that CCDC167 is a novel and potentially valuable prognostic marker for hepatocellular carcinoma, and that CCDC167 iCCDC167 not only promotes hepatocellular carcinoma cell proliferation but is also associated with immune function in hepatocellular carcinoma patients.

Serum Clusterin Level as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is the third deadliest and fifth most common cancer worldwide, despite the widespread use of surveillance programs in at risk populations, more than half of HCC cases are diagnosed late, and curative therapies such as surgical resection, radiofrequency ablation (RFA) or TACE are possible in less than 30% of patients. Objective To assess the diagnostic and prognostic role of detection of serum Clusterin as a biomarker of hepatocellular carcinoma among the Egyptian patients before and after interventional treatment. Patients and Methods This study has been carried out in the department of Internal Medicine and Gastroenterology in Ain Shams University Hospitals and Hepatology department in Manshiyet El Bakry General Hospital in the period between July to December 2020. Results There was significant positive correlation between Clusterin and the mRecist score with pvalue (&amp;lt;0.001) where it increases with advancing in stages. Conclusion AFP is significantly elevated in HCC groups than in cirrhotic (control) and with better sensitivity and specificity than Clusterin. Clusterin has significant positive correlation with Mrecist score of HCC patients which means it acts better as a prognostic tool for following HCC patients. Patients who had recurrence in both HCC groups (RF and TACE) showed less decrease in Clusterine level than those with non-recurrence among both groups. Serum clusterin level was significantly higher among patients with progressive disease (PD) than those with partial response (PR) than those with complete response (CR). Also follow up serum clusterin level after intervention was statistically significant higher among patients with progressive disease (PD) than those with partial response (PR) than those with complete response (CR).

Dickkopf-1 (DKK1): A Diagnostic Marker for Hepatocellular Carcinoma (HCC) on Top of Chronic Hepatitis C Virus Related Diseases

Abstract Background Hepatocellular carcinoma (HCC) is a common form of cancer in the world and is the third leading cause of cancer-related death. More than 80% of its incidence is found in developing countries; rates are more than twice as high in men compared with women. HCC is the most common form among primary liver cancers occurring worldwide, about 70–85% of liver tumors. Aim of the Work This study was aimed to evaluate the clinical significance of serum Dickkopf-1 (DKK1) as a diagnostic and prognostic marker in hepatocellular carcinoma. Patients and Methods This was a prospective study that was conducted on 60 patients and 30 healty control subjects recruited from Al Sahel Teaching Hospital. Results Regarding the demographic data, there was no statistically significant difference found between 3 groups regarding age and sex. Tumor Size was &amp;lt; 2 cm in 10.0% of HCC patients, 2 – 3 cm in 56.7% of them &amp; &amp;gt; 5 cm in 33.3% of HCC patients. While number of tumors was Single in 33.3% of HCC patients, 2 – 3 in 30.0% &amp; Multiple masses in 36.7% of patients. PV thrombosis was reported in 30% of patients. Incidence of child score c in our study was significantly higher in HCC Group when compared with Liver Cirrhosis group. According to this study, there was Non statistically significant correlation Between DKKA1 (pg/ml) &amp; each of Age, HB, WBCs, Platelets, ALT, AST, Creat, Urea, Albumin, INR, Bilirubin and AFP in both all patients &amp; Liver Cirrhosis groups. While for HCC group, there was Non statistically significant correlation Between DKKA1(pg/ml), Age, HB, Platelets, ALT, Creat, Urea, Albumin, INR, Bilirubin and AFP, but there was statically significant Positive correlation Between DKKA1(pg/ml), WBCs and AST. Serum DKK1 was significantly higher in HCC group comparing with liver cirrhosis group and control group. According to our study, ROC curve showed that the best cut off point of DKKA1 to detect Liver Cirrhosis group was &amp;gt; 264.9 pg/ml with sensitivity of 56.67%, specificity of 86.67%, PPV of 81.0%, NPV of 66.7%. Another ROC curve showed that the best cut off point of DKKA1 to detect HCC group was found &amp;gt; 453 with sensitivity of 83.33%, specificity of 93.33%, PPV of 92.6%, NPV of 84.8%. Assessment of diagnostic performance of serum DKK1 when used in discriminating Group (HCC) from Group (Liver Cirrhosis), revealed a better diagnostic performance of DKK1) as the best ROC cut-off for DKK1 was &amp;gt; 1674.8 ng/mL, this had a diagnostic sensitivity of 50%, specificity 96.67%, positive predictive value 93.7%, negative predictive value 65.9%. Conclusion In conclusion, our study suggests that DKK-1 may be a key regulator in HCC progression, a promising potential therapeutic target for HCC. We also demonstrated that serum DDK-1 could be a useful marker for diagnosing HCC.

Thymidine kinase 1 appears to be a marker for the prognosis of hepatocellular carcinoma based on a large-scale, multicenter study.

The aim of this study was to investigate the role of thymidine kinase 1 (TK1) levels in hepatocellular carcinoma (HCC) prognosis and to develop a nomogram for predicting HCC prognosis. In this study, 1066 HCC patients were enrolled between August 2018 and April 2022. TK1 levels were measured within one week before enrollment, and the relationship with HCC prognosis was evaluated. Next, all patients were randomly assigned to the training set (70%, n=746) and the validation set (30%, n=320). We used multivariate Cox analysis to find independent prognostic factors in the training set to construct a nomogram. The predictive power of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The optimal critical value of TK1 was determined as 2.35 U/L using X-tile software. Before and after propensity score matching (PSM), the median overall survival (mOS) of the low-TK1 group (<2.35U/L) remained significantly longer than that of the high-TK1 group (≥ 2.35U/L) (48.1 vs 16.5 months, p < 0.001; 75.7 vs 19.8 months, p = 0.001). Moreover, multivariate Cox analysis showed that the low TK1 level was an independent positive prognostic indicator. Additionally, the area under the ROC curve for predicting the 1-year, 2-year, and 3-year survival rates was 0.770, 0.758, and 0.805, respectively. TK1 could serve as a prognostic marker for HCC. In addition, the nomogram showed good predictive capability for HCC prognosis.

Relationship between STAP1 methylation in peripheral blood T cells and the clinicopathological characteristics and prognosis of patients within 5-cm diameter HCC.

The aim of this study is to explore the methylation of signal transduction adaptor protein 1 (STAP1) in peripheral blood T cells as a prognostic marker for hepatocellular carcinoma (HCC) ≤5 cm. A total of 66 HCC patients who visited our hospital from November 2012 to June 2016 were retrospectively analyzed, and 55 patients who met the inclusion and exclusion criteria were studied. Clinical and pathological data were collected from all patients to detect STAP1 methylation. STAP1 methylation expression was analyzed in HCC patients ≤5 cm with different clinicopathological features; univariate and independent prognostic factors were analyzed in HCC patients; and the relationship between STAP1 methylation expression and prognosis was analyzed in HCC patients. There was no significant difference in STAP1 methylation expression between patients with different gender, age, history of alcoholism, history of liver cirrhosis, recurrence, 3-year OS, 5-year OS, treatment, number of tumors, tumor diameter, HBV-DNA, HBSAg, Hbe-Ag expression, and AFP level (P>0.05); however, there was significant difference in STAP1 methylation expression between patients with different survival, 3-year DFS, and 5-year DFS (P<0.05). Multivariate Cox regression analysis showed that recurrence and STAP1 methylation were independent factors for OS and DFS (P<0.05). Kaplan-Meier survival curve results showed that the median survival time, OS, and DFS of STAP1 hypermethylation expression were shorter than those of hypomethylation (P<0.05). STAP1 methylation in peripheral blood T cells serves as a potential prognostic marker for HCC ≤5 cm.

Retracted: Identification and Validation of an Inflammatory Response-Related Polygenic Risk Score as a Prognostic Marker in Hepatocellular Carcinoma.

[This retracts the article DOI: 10.1155/2022/1739995.].

Identification of KNOP1 as a prognostic marker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. This study aimed to evaluate the role and molecular mechanism of lysine-rich nucleolar protein 1 (KNOP1) in HCC. Data from The Cancer Genome Atlas (TCGA), genotype-tissue expression (GTEx), and Gene Expression Omnibus (GEO) databases were used to compare KNOP1 expression in normal and HCC tissues. The Human Protein Atlas (HPA) database was used to verify KNOP1 protein expression. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment, protein-protein and gene-gene interaction network, DNA methylation, genetic alteration, and immune cell infiltration analyses were used to analyze the function and pathway enrichment of KNOP1. Finally, receiver operating characteristic (ROC) curves, Kaplan-Meier (KM) analysis, univariate/multivariate Cox regression analyses, and nomograms were used to predict the clinical and prognostic significance of KNOP1. KNOP1 expression was higher in HCC tissue samples than in normal specimens. Additionally, high KNOP1 expression was positively correlated with T helper 2 (Th2) cells and immune checkpoints. KM analysis, Cox regression analysis, and nomogram prognostic model prediction suggested that high KNOP1 expression is a risk factor for poor HCC prognosis. KNOP1 overexpression is associated with poor HCC prognosis and increased proportions of immune cell infiltration and checkpoints. KNOP1 is a potential biomarker for evaluating HCC prognosis.

Vitronectin (VTN): A Novel Diagnostic and Prognostic Marker for Hepatocellular Carcinoma (HCC) on Top of Chronic Hepatitis C Virus Related Diseases

Vitronectin (VTN): A Novel Diagnostic and Prognostic Marker for Hepatocellular Carcinoma (HCC) on Top of Chronic Hepatitis C Virus Related Diseases

A novel approach for the analysis of single-cell RNA sequencing identifies TMEM14B as a novel poor prognostic marker in hepatocellular carcinoma

A fundamental goal in cancer-associated genome sequencing is to identify the key genes. Protein–protein interactions (PPIs) play a crucially important role in this goal. Here, human reference interactome (HuRI) map was generated and 64,006 PPIs involving 9094 proteins were identified. Here, we developed a physical link and co-expression combinatory network construction (PLACE) method for genes of interest, which provides a rapid way to analyze genome sequencing datasets. Next, Kaplan‒Meier survival analysis, CCK8 assays, scratch wound assays and Transwell assays were applied to confirm the results. In this study, we selected single-cell sequencing data from patients with hepatocellular carcinoma (HCC) in GSE149614. The PLACE method constructs a protein connection network for genes of interest, and a large fraction (80%) of the genes (screened by the PLACE method) were associated with survival. Then, PLACE discovered that transmembrane protein 14B (TMEM14B) was the most significant prognostic key gene, and target genes of TMEM14B were predicted. The TMEM14B-target gene regulatory network was constructed by PLACE. We also detected that TMEM14B-knockdown inhibited proliferation and migration. The results demonstrate that we proposed a new effective method for identifying key genes. The PLACE method can be used widely and make outstanding contributions to the tumor research field.

FKBP11 upregulation promotes proliferation and migration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients' outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients' clinical characteristics and potential role in HCC development. Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate involvement in HCC development. FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p< 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823-0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p< 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC.