Expression of telomerase-associated protein 1 and telomerase reverse transcriptase in hepatocellular carcinoma

To know whether two protein components of human telomerase (human telomerase-associated protein 1 (hTEP1) and human telomerase reverse transcriptase (hTERT) are useful markers for telomerase activation in human liver diseases, we examined mRNA levels of these and telomerase activity in human liver samples. Twenty-three human hepatocellular carcinomas (HCCs) and corresponding adjacent livers were analysed for hTEP1 and hTERT expression by semiquantitative reverse transcription-polymerase chain reaction, and for telomerase activity by a telomeric repeat amplification protocol assay. Thirteen liver samples (ten HCCs and three dysplastic nodules) that were biopsied with 21-gauge needles were analysed for hTERT expression. hTEP1 was expressed in all samples examined. No correlation between hTEP1 expression and telomerase activity was observed. hTERT expression significantly correlated with telomerase activity (P< 0.001). The positivity of hTERT for HCC and corresponding non-cancerous liver was 100% and 30.4% respectively (P< 0.001). Seventy-four per cent (17/23) of HCCs showed strong hTERT expression, but none of the non-cancerous liver tissues did. hTERT expression of the 21-gauge needle biopsied specimens showed no significant difference from that of the surgical samples. The present study revealed that hTERT is strongly expressed in most HCCs, and that hTERT but not hTEP1 is a key component regulating telomerase activity in human liver. © 2000 Cancer Research Campaig

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib

Background: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy

Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma

MAGE gene family encodes peptides recognized by autologous cytotoxic T lymphocytes in a major histocompatibility complex (MHC) class-I restricted fashion. In the present study, we have performed reverse-transcription polymerase chain reaction (RT-PCR) for the genes, as well as immunohistochemical analysis and Western blotting of MAGE-1 and -3 proteins in 33 surgically resected hepatocellular carcinomas (HCCs). MAGE-1 and -3 mRNAs were constitutively expressed exclusively in 78 and 42% of HCCs respectively. On immunohistochemistry with monoclonal antibodies, 77B for MAGE-1 and 57B for MAGE-3, MAGE-1 and -3 proteins were recognized in cytoplasm of only six among 33 (18%) and two of 29 HCCs (7%) respectively. The distribution pattern was mostly focal in HCC nodules. By contrast, the Western blot analysis revealed that the MAGE-1 (46 kDa) and -3 proteins (48 kDa) were expressed in 80 and 60% of 15 HCCs examined respectively. The proteins of MAGE-1 and -3 were also expressed exclusively in HCCs regardless of the histological grading and clinical staging. Our results indicate that the detection of the genes by RT-PCR or the proteins by Western blotting is useful for differentiating early HCCs from non-cancerous lesions, and that the peptides derived from MAGE-1 and -3 proteins might be suitable targets for immunotherapy of human HCC. © 1999 Cancer Research Campaig