Severity Of Hepatocellular Carcinoma Research Articles

Determination of correlation between cytokines IL 6, IL8, IL10, IL12, IL17 and severity of hepatocellular carcinoma in patients having hepatitis C.

To determine the correlation between the levels of interleukins 6, 8, 10, 12 and 17 and the severity of hepatocellular carcinoma in patients positive for hepatitis C. The retrospective, cross-sectional, analytical study was conducted at the Department of Medicine, Mardan Medical Complex, Mardan, Khyber Pakhtunkhwa, Pakistan, and comprised data of hepatocellular carcinoma patients who were positive for hepatitis C on polymerase chain reaction test from March 2021 to December 2022. A control group of healthy patients was also included. The severity of hepatocellular carcinoma was assessed using the Barcelona Clinic Liver Cancer method, and the patients were classified into five stages: very early stage 0, earlystage A, intermediate-stage B, advanced-stage C, and end-stage D. Interleukin 6, 8, 10, 12 and 17 levels and disease severity were correlated using Pearson correlation coefficient. Data was analysed using SPSS 26. Of the 115 subjects, 67(58.3%) were patients and 48(41.7%) were controls. There were 72(62.6%) males and 43(37.4%) females. The median age of patients was 56 years (interquartile range: 38-64 years), and among the cases it was 36 years (interquartile range: 32-44 years). Among the patients, 8(11.94%) were at stage 0, 11(16.41%) stage A, 24(35.82%) stage B, 13(19.40%) stage C, and 11(16.41%) stage D. Intergroup differences indicated a significant difference, with interleukin levels being higher in patients with more advanced stages (p<0.05). </AbstractText> <AbstractText Label="CONCLUSIONS">The use of interleukin levels as biomarkers could facilitate earlier detection of advanced-stage disease, leading to more timely interventions and potentially improving patient outcomes.

Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1 (TGF-β1) availability and inhibits hepatocarcinogenesis.

Increased Galectin 3-binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway. The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis. The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice. In patients with MASH and HCC, the levels of LGALS3BP and TGFB1 exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton. The released TGF-β1 activated JunB transcription factor, which in turn promoted the TGF-β1 positive feedback loop. LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis. Moreover, LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1. LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway, making it a promising therapeutic target in TGF-β1-related diseases.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

Unawareness of hepatitis B infection and lack of surveillance are associated with severity of hepatocellular carcinoma.

Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

Retracted: The Relationship between Ultrasonographic Features of Hepatocellular Carcinoma and the Severity of Hepatocellular Carcinoma and the Expression of PTEN and Tg737.

[This retracts the article DOI: 10.1155/2022/2608633.].

The Relationship between Ultrasonographic Features of Hepatocellular Carcinoma and the Severity of Hepatocellular Carcinoma and the Expression of PTEN and Tg737.

To investigate the relationship between the ultrasonographic features of hepatocellular carcinoma (HCC) and the severity of HCC and the expression of tumor suppressor genes PTEN and Tg737, 90 patients with primary liver cancer are selected as the study subjects. The enhancement of liver tumor in arterial phase, portal venous phase, and delayed phase is observed by contrast-enhanced ultrasound (CEUS) before operation, and the echo intensity is compared with that of surrounding liver parenchyma. Immunohistochemistry is used to detect the expression of PTEN and Tg737 in hepatocellular carcinoma and paracancerous tissues. (1) In HCC, CEUS enhancement is characterized by rapid enhancement in arterial phase, enhancement in portal venous phase and delayed phase, and decreased hypoechoic changes. About 78.0% of the stage I-II liver cancer and 85.0% of the stage III-IV liver cancer show rapid enhancement and high echo in the arterial phase; only 8.0% of the stage I-II liver cancer shows moderate echo changes in the portal venous phase, while 32.5% (13/40) stage III-IV liver cancer shows moderate echo changes in the portal venous phase. (2) The positive rates of PTEN in liver cancer tissues and paracancerous tissues are 21.1% (19/90) and 70.0% (63/90), respectively, and the difference is statistically significant. The positive rates of Tg737 in liver cancer tissues and paracancerous tissues are 17.8% (16/90) and 75.6% (68/90), respectively, and the difference is statistically significant. Compared with PTEN and Tg737 negative groups, the ascending slope (RS) and initial elimination time (WT) of PTEN and Tg737 positive groups are significantly higher, indicating that the inflow velocity of contrast medium in the positive group is higher, the outflow time is shorter, and the lesions shows low enhancement rapidly. However, the expression of PTEN and Tg737 had no significant difference in maximal intensity (IMAX), peak time (TTP), and mean transit time (mTT). (3) Correlation analysis shows that the immunohistochemical scores of PTEN and Tg737 are not significantly correlated with IMAX, mTT, and TTP but positively correlated with RS (r = 0.359,P < 0.05), suggesting that the positive expressions of PTEN and Tg737 are negatively correlated with the inflow velocity of contrast medium. The immunohistochemical scores of PTEN and Tg737 are negatively correlated with WT, which indicated that the higher the expression intensity of PTEN is, the longer the outflow time of contrast medium is and the slower the outflow of contrast medium is. There is a significant correlation between the expression of PTEN and Tg737 proteins and CEUS parameters in hepatocellular carcinoma.

Facilitatory effect of insulin treatment on hepatocellular carcinoma development in diabetes

BackgroundTo evaluate the effect of insulin treatment on the incidence and/or severity of hepatocellular carcinoma (HCC) in a mouse model of HCC based on diabetes.MethodsWe recently reported that neonatal streptozotocin (STZ) treatment causes type 1 diabetes and subsequent HCC in ddY, Institute for Animal Reproduction (DIAR) mice. Newborn male DIAR mice were divided into three groups based on STZ and insulin (INS) treatment. STZ was subcutaneously injected (60 mg/g) into the STZ-treated group (DIAR-nSTZ mice, N = 13) and the STZ/insulin-treated group (DIAR-nSTZ/INS mice, N = 20). A physiologic solution was injected into the control group (DIAR-control mice, N = 8) 1.5 days after birth. Insulin was subcutaneously injected into the DIAR-nSTZ/INS mice according to the following protocol: 2 IU/day at 4–5 weeks of age, 3 IU/day at 5–7 weeks of age, and 4 IU/day at 7–12 weeks of age. All mice were fed a normal diet and were subjected to physiological and histopathological assessments at 12 weeks of age.ResultsDIAR-nSTZ mice had significantly lower body weight and higher blood glucose levels than DIAR-control mice, whereas no significant differences were observed between DIAR-nSTZ/INS mice and control mice. At 12 weeks of age, lower weight of paratesticular fat and higher levels of total cholesterol, triglyceride, and free fatty acids were observed in DIAR-nSTZ mice compared to DIAR-control mice, whereas there were no significant differences between DIAR-nSTZ/INS mice and DIAR-control mice. In the livers of DIAR-nSTZ mice, HCC was observed in 15% of cases, and dysplastic nodules were observed in 77% of cases. In the livers of DIAR-nSTZ/INS mice, HCC was observed in 39% of cases and dysplastic nodules were observed in 61% of cases (p = 0.011). Moreover, the average tumor size was significantly larger in STZ/INS-treated mice than in STZ-treated mice. Immunohistochemical analysis demonstrated that the expression of ERK1/2, downstream substrates of insulin signaling that activate cell proliferation, was significantly higher in STZ/INS-treated mice compared to STZ-treated mice.ConclusionsInsulin treatment promoted, rather than inhibited, the progression of liver carcinogenesis in DIAR-nSTZ mice. Hyperinsulinemia rather than hyperglycemia can accelerate the progression of HCC via insulin signaling.

Relationship Between Vascular Endothelial Growth Factor and Severity of Hepatocellular Carcinoma

Background: Severity of hepatocellular carcinoma (HCC) that is assessed using Barcelona Clinic Liver Cancer (BCLC) classification is a main prognostic factor of hepatocellular carcinoma. Assessment of the serum level of Vascular Endothelial Growth Factor (VEGF) is considered to reflect the severity of HCC. However, there is still no fundamental basis of the association of severity of HCC with the serum VEGF level. The objective of this study is to know the relationship between serum VEGF levels with the severity of HCC by assessing the average difference of serum VEGF level in various severity of HCC.Method: This study was a cross sectional study to identify the association between serum VEGF levels with the severity of HCC based on BCLC classification. This study was performed in Cipto Mangunkusumo Hospital between January and May 2015. Statistical tests used to evaluate the association between serum VEGF level with BCLC classification was one-way ANOVA analysis, and continued with post hoc Tukey Schaffe analysis.Results: A total of 61 subjects with HCC were included into this study. In this study, we did not find subjects with stage 0 BCLC. The average of serum VEGF level in stage A BCLC was 288.26 ± 156.6 pg/mL; stage B BCLC: 434 ± 164.8 pg/mL; stage C BCLC: 785.57 ± 194.25 pg/mL; stage D BCLC: 1537.97 ± 660.62 pg/mL. One-way ANOVA analysis showed significant difference (P 0.001) between serum VEGF level and HCC severity based on BCLC classification. Post hoc Tukey Schaffe analysis showed the presence of significant difference between stage A and C BCLC (p 0.05) and stage A and D BCLC (p 0.001), stage B and D BCLC (p 0.001), and stage C and D BCLC (p 0.001). There was no significant difference between stage A and B BCLC, and between stage B and C BCLC.Conclusion: It was found that serum VEGF level increased in accordance to the HCC severity based on BCLC classification, particularly for stage B BCLC and above.

Alleles and genotypes of polymorphisms of IL-18, TNF-α and IFN-γ are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607(*)A (P=0.0235; OR=1.48; 95%CI=1.06-2.08); TNF-α -238(*)A (P=0.0025; OR=2.12; 95%CI=1.32-3.40) and TNF-α -308(*)A (P=0.0351; OR=1.82; 95%CI=1.07-3.08); and genotypes IL-18-607AA (P=0.0048; OR=3.03; 95%CI=1.40-6.55); TNF-α -238GA (P=0.0011; OR=2.44; 95%CI=1.45-4.12); and TNF-α -308GA (P=0.0031; OR=2.51; 95%CI=1.39-4.51). Significant association was found between multinodular HCC and IL-18 -607(*)C allele (P=0.029; OR=2.40, 95%CI: 1.09-5.28), and IL-18 -607CC genotype (P=0.028; OR=3.5, 95%CI: 1.24-9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P=0.044; OR=3.6, 95%CI: 1.03-12.47). The IL-18 -137(∗)C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607(*)A and TNF-α (-238(*)A and -308(*)A) alleles may confer susceptibility to HCC, while IL-18 -607(*)C and -137(*)C alleles more severe disease.

Correlation between epigenetic alterations in the insulin growth factor-II gene and hepatocellular carcinoma

To investigate whether epigenetic alterations in the insulin-like growth factor-II (IGF-II) gene that cause differential transcription or expression are correlated with onset and severity of hepatocellular carcinoma (HCC). Patient-matched specimens of HCC, paracancerous, and non-cancerous tissues were collected from 40 primary liver cancer patients. Epigenetic alterations in the promoter (P3) sequence of the IGF-II gene were analyzed by methylation-specific PCR (MSP) and IGF-II transcription was measured by RT-PCR. IGF-II protein expression and clinicopathological features were assessed by immunohistochemistry and microscopic observation. The rate of IGF-II P3 methylation was significantly lower in HCC tissues (0%) than in paracancerous tissues (vs. 47.5%; x2 = 24.918, P less than 0.001) and non-cancerous tissues (vs. 100%; x2 = 80.000, P less than 0.001). IGF-II mRNA expression was significantly higher in HCC tissues (100%) than in paracancerous tissues (vs. 52.5%; x2 = 24.918, P less than 0.001) and non-cancerous tissues (vs. 0%; x2 = 80.000, P less than 0.001). IGF-II protein expression was significantly higher in HCC tissues (82.5%) than in paracancerous tissues (vs. 45.0%; x2 = 12.170, P less than 0.001) and non-cancerous tissues (vs. 0%; x2 = 56.170, P less than 0.001). IGF-II overexpression in HCC was significantly associated with degree of differentiation, extent of infiltrated serosa, size of tumor, and HBV-positive infection status. Epigenetic alterations in the IGF-II gene regulate its transcription and expression and are closely associated with HCC development and progression.

Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach.

The severity of hepatocellular carcinoma (HCC) and the lack of good diagnostic markers and treatment strategies have rendered the disease a major challenge. Previous microarray analyses of HCC were restricted to the selected tissue sample sets without validation on an independent series of tissue samples. We describe an approach to the identification of a composite discriminator cassette by intersecting different microarray datasets. We studied the global transcriptional profiles of matched HCC tumor and nontumor liver samples from 37 patients using cDNA (cDNA) microarrays. Application of nonparametric Wilcoxon statistical analyses (P < 1 x 10(-6)) and the criteria of 1.5-fold differential gene expression change resulted in the identification of 218 genes, including BMI-1, ERBB3, and those involved in the ubiquitin-proteasome pathway. Elevated ERBB2 and epidermal growth factor receptor (EGFR) expression levels were detected in ERBB3-expressing tumors, suggesting the presence of ERBB3 cognate partners. Comparison of our dataset with an earlier study of approximately 150 tissue sets identified multiple overlapping discriminator markers, suggesting good concordance of data despite differences in patient populations and technology platforms. These overlapping discriminator markers could distinguish HCC tumor from nontumor liver samples with reasonable precision and the features were unlikely to appear by chance, as measured by Monte Carlo simulations. More significantly, validation of the discriminator cassettes on an independent set of 58 liver biopsy specimens yielded greater than 93% prediction accuracy. In conclusion, these data indicate the robustness of expression profiling in marker discovery using limited patient tissue specimens as well as identify novel genes that are highly likely to be excellent markers for HCC diagnosis and treatment.