Correlation Of Hepatocellular Carcinoma Research Articles

Identification and Validation of a Tumor Microenvironment-Related Gene Signature in Hepatocellular Carcinoma Prognosis.

Background: Hepatocellular carcinoma (HCC) is a typical inflammatory-related malignant tumor with complex immune tolerance microenvironment and poor prognosis. In this study, we aimed to construct a novel immune-related gene signature for the prognosis of HCC patients, exploring tumor microenvironment (TME) cell infiltration characterization and potential mechanisms. Methods: A total of 364 HCC samples with follow-up information in the TCGA-LIHC dataset were analyzed for the training of the prognostic signature. The Least Absolute Shrinkage and Selector Operation (LASSO) regression based on the IRGs was conducted to identify the prognostic genes and establish an immune risk signature. The immune cell infiltration in TME was estimated via the CIBERSORT method. Gene Set Variation Analysis (GSVA) was conducted to compare the biological pathways involved in the low-risk and high-risk groups. Furthermore, paraffin sections of HCC tissue microarrays containing 77 patients from Fudan University Shanghai Cancer Center were used for IHC staining. The clinical characteristics of the 77 HCC patients were collected and summarized for survival analysis validation via the Kaplan–Meier (KM) method. Results: Three-gene signature with close immune correlation (Risk score = EPO * 0.02838 + BIRC5 * 0.02477 + SPP1 * 0.0002044) was constructed eventually and proven to be an effective prognostic factor for HCC patients. The patients were divided into a high-risk and a low-risk group according to the optimal cutoff, and the survival analysis revealed that HCC samples with high-risk immuno-score had significantly poorer outcomes than the low-risk group (p < 0.0001). The results of CIBERSORT suggested that the immune cell activation was relatively higher in the low-risk group with better prognosis. Besides, GSVA analysis showed multiple signaling differences between the high- and low-risk group, indicating that the three-gene prognostic model can affect the prognosis of patients by affecting immune-related mechanisms. Tissue microarray (TMA) results further confirmed that the expression of three genes in HCC tissues was closely related to the prognosis of patients, respectively. Conclusion: In this study, we constructed and validated a robust three-gene signature with close immune correlation in HCC, which presented a reliable performance in the prediction of HCC patients’ survival.

Correlation of Hepatocellular Carcinoma with Different Levels of Alpha-Fetoprotein in Pakistani Population

Objective: To assess pathological, biochemical and clinical parameters in HCC patients with low, normal and high AFP levels. Methodology: This comparative analytical study was conducted in Liver and Gastric Clinic, Holy Family Hospital, Rawalpindi from June 2019-June 2020.Sample size was calculated as 225 by WHO sample size calculator . Non randomized convenient sampling was used. Patients were divided into three groups according to AFP values; &lt;200 ng/ml, 200-400ng/ml and &gt;400 ng/ml. Patients demographic details, medical history, clinical symptoms and signs, biochemical parameters and pathological findings on ultrasonography and CECT were assessed. Data was analyzed by SPSS version 21. Descriptive statistics were calculated for categorical  variable.  p Value less than 0.05 was considered significant. Results: Out of 256 patients, 161 (62.9%) were males and 95 (37.1%) were females.The mean age of patients was 60.5 years ± 10.5. 94.4% of patients with HCC had Hepatitis C. Anorexia, jaundice and abdominal distension, hepatomegaly and splenomegaly were more frequent in patients having high AFP level. Serum bilirubin, tumor size, number of lesions, BCLC staging and other pathological parameters associated with HCC worsens as AFP levels increase. Conclusion: Alpha-fetoprotein levels are significantly associated with clinical and pathological parameters of hepatocellular carcinoma thus can be used as a better diagnostic and prognostic tool.

Pathological considerations of CEUS LI-RADS: correlation with fibrosis stage and tumour histological grade.

To evaluate the influence of pathological factors, such as fibrosis stage and histological grade, on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasonography (CEUS) in patients with high risk of hepatocellular carcinoma (HCC). Between June 2015 and December 2016, 441 consecutive patients at high risk of HCC with 460 pathologically proven HCCs were enrolled in this retrospective study. All patients underwent a CEUS examination. The major features (arterial phase hyperenhancement, late and mild washout) were assessed, and LI-RADS categories were assigned according to CEUS LI-RADS v2017. CEUS LI-RADS categories and major features were compared in different histological grades and fibrosis stages. The CEUS LR-5 category was more frequently assigned in the low-grade group (151/280) than in the high-grade group (66/159) (p = 0.013), whereas the LR-TIV category was more frequently assigned in the high-grade group (36/159) than in the low-grade group (40/280) (p= 0.035). CEUS LI-RADS category was not significantly different among different fibrosis stages (p ≥ 0.05). Arterial phase hyperenhancement (APHE) and the hepatic fibrosis stage showed a significant correlation in HCCs ≥ 2cm and the low-grade group (p= 0.027 and p= 0.003, respectively). No major features of CEUS LI-RADS showed statistically significant differences between the low- and high-grade groups (p≥ 0.05). Hepatic fibrosis stage can influence APHE but showed no impact on the CEUS LI-RADS classification, whereas the histological grade of HCC influenced the LR-5 and LR-TIV categories. • Histological grade influenced CEUS LR-5 and LR-TIV category (p = 0.013 and p = 0.035 respectively). Low-grade HCCs occurred more frequently in LR-5 category whereas high-grade HCCs occurred more frequently in LR-TIV category. • Fibrosis stage shows significant influence on APHE on HCCs of the size ≥ 2cm and low-grade group (p = 0.027 and p = 0.003, respectively). • Hepatic fibrosis stage and HCC histological grade exhibited limited impact on CEUS LI-RADS. CEUS LI-RADS may be feasible for diagnosing HCC in patients regardless of histological grade and fibrosis stage.

E3 Ubiquitin Ligase APC/CCdh1 Regulation of Phenylalanine Hydroxylase Stability and Function.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by the dysfunction of the enzyme phenylalanine hydroxylase (PAH). Alterations in the level of PAH leads to the toxic accumulation of phenylalanine in the blood and brain. Protein degradation mediated by ubiquitination is a principal cellular process for maintaining protein homeostasis. Therefore, it is important to identify the E3 ligases responsible for PAH turnover and proteostasis. Here, we report that anaphase-promoting complex/cyclosome-Cdh1 (APC/C)Cdh1 is an E3 ubiquitin ligase complex that interacts and promotes the polyubiquitination of PAH through the 26S proteasomal pathway. Cdh1 destabilizes and declines the half-life of PAH. In contrast, the CRISPR/Cas9-mediated knockout of Cdh1 stabilizes PAH expression and enhances phenylalanine metabolism. Additionally, our current study demonstrates the clinical relevance of PAH and Cdh1 correlation in hepatocellular carcinoma (HCC). Overall, we show that PAH is a prognostic marker for HCC and Cdh1 could be a potential therapeutic target to regulate PAH-mediated physiological and metabolic disorders.

Immune infiltration-associated serum amyloid A1 predicts favorable prognosis for hepatocellular carcinoma.

BACKGROUNDSerum amyloid A1 (SAA1) is an acute-phase protein involved in acute or chronic hepatitis. Its function is still controversial. In addition, the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma (HCC) is still unclear.AIMTo demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODSSAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) in GEPIA tool, and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal. The high or low expression group was then drawn based on the median level of SAA1 expression. The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC, including tumor grade, patient disease stage, and the TP53 mutation. The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal. The tumor purity score and the immune score were analyzed with CIBERSORT. The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions. GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy. Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC. The similar genes of SAA1 in HCC were identified in GEPIA, and the protein-protein interaction of SAA1 was conducted in the Metascape tool. The expression of C-X-C motif chemokine ligand 2, C-C motif chemokine ligand 23, and complement C5a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal, respectively.RESULTSSAA1 expression was decreased in HCC, and lower SAA1 expression predicted poorer overall survival, progression-free survival, and disease-specific survival. Furthermore, SAA1 expression was further decreased with increased tumor grade and patient disease stage. Also, SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53. SAA1 expression was negatively correlated with the TP53 mutation. Lower SAA1 predicted poorer survival rate, especially in the patients with no hepatitis virus infection, other than those with hepatitis virus infection. Moreover, the SAA1 expression was negatively correlated with tumor purity. In contrast, SAA1 expression was positively correlated with the immune score in HCC, and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC. Decreased SAA1 was closely associated with the immune tolerance of HCC. C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1, which could also serve as favorable prognosis markers for HCC.CONCLUSIONSAA1 is downregulated in the liver tumor, and it is closely involved in the progression of HCC. Lower SAA1 expression indicates lower survival rate, especially for those patients without hepatitis virus infection. Lower SAA1 expression also suggests lower immune infiltrating cells, especially for those with immune cells exerting anti-tumor immune function. SAA1 expression is closely associated with the anti-tumor immune pathways.

MiR-139-5p influences hepatocellular carcinoma cell invasion and proliferation capacities via decreasing SLITRK4 expression.

The microRNA, miR-139-5p, has been proved to play important roles in regulating tumor progression, including prostate cancer, osteosarcoma, esophageal cancer, and so on, but its correlation of hepatocellular carcinoma (HCC) still remains unclear. Here we found that hsa-miR-139-5p (miR-139-5p) was decreased in HCC samples compared with normal liver tissues, and a lower expression of miR-139-5p was connected to a poorer prognosis. Mechanism study indicated that a decreased/increased miR-139-5p could increase/decrease HCC cells invasion and proliferation capacities via increasing SLITRK4 expression, what’s more, the reverse assays also confirmed the conclusion when we knocked down SLITRK4 in the miR-139-5p low-expression cells. Luciferase assay confirmed that miR-139-5p could directly bind to the 3′UTR of SLITRK4 mRNA to regulate its expression. Together, these findings show the importance of miR-139-5p/SLITRK4 pathway in HCC growth and progression and may provide new targets for us to better arrange the progression of HCC.

Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study...

Radiological-pathological correlation study of hepatocellular carcinoma undergoing local chemoradiotherapy and surgery.

Optimal response criteria and assessment timing were investigated through radiologic-pathologic correlation in hepatocellular carcinoma (HCC) treated with localized chemoradiotherapy (CRT). We reviewed 19 consecutive HCC patients who underwent surgical resection after radiotherapy and concurrent hepatic arterial infusion chemotherapy. Patients who received transarterial chemoembolization before RT or surgery were excluded from evaluation. Tumor diameters and total and enhancing tumor volumes were measured from CT images obtained 1, 3, 6, and 9 months after CRT. Percent changes calculated using size (RECIST and WHO) and enhancement criteria (mRECIST and EASL) were correlated with percent changes in total and enhancing tumor volumes, and with percent viable tumor in surgical specimens. Median time between CRT and resection was 4.1 months (range, 1.5-15.4 months). CR and PR rates were 0 and 68% by RECIST, 0 and 63% by WHO, 53% and 37% by mRECIST, and 53% and 42% by EASL. Pathologic CR (pCR) rate was 52.6%. Radiologic criteria showed strong correlation with tumor volumes at 1 and 3 months after CRT; at 6 months, however, size and enhancement criteria showed strong correlation only with total and enhancing tumor volumes, respectively. Enhancement criteria were better predictors of pathologic response at all times including preoperative evaluation (RECIST: R(2) = 0.303, P = 0.015 and WHO: R(2) = 0.366, P = 0.006 vs. mRECIST: R(2) = 0.760, P < 0.0001 and EASL: R(2) = 0.768, P < 0.0001). Time interval >6 months before resection showed significant correlation with pCR (P = 0.013). We recommend using enhancement criteria in assessing tumor viability, especially if the tumor was to be resected <6 months after CRT.

Genome-wide integrative analysis revealed a correlation between lengths of copy number segments and corresponding gene expression profile.

Microarray analysis has been applied to comprehensively reveal the abnormalities of DNA copy number (CN) and gene expression in human cancer research during the last decade. These analyses have individually contributed to identify the genes associated with carcinogenesis, progression, metastasis of tumor cells and poor prognosis of cancer patients. However, it is known that the correlation between profiles of CN and gene expression does not highly correlate. Factors which determine the degree of correlation remain largely unexplained. To investigate one such factor, we performed trend analyses between the lengths of CN segments and corresponding gene expression profiles from microarray data in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC). Significant correlations were observed in CN gain of HCC and CRC (p<0.05). The trend of the CN loss showed a significant correlation in HCC although there was no correlation between the length of CN loss segments and gene expression in CRC. Our findings suggest that the influence of CN on gene expression highly depends on the length of CN region, especially in the case of CN gain. To the best of our knowledge, this is the first study describing the correlation between lengths of CNA segments and expression profiles of corresponding genes.