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Background: Hepatocellular carcinoma (HCC) is an aggressive carcinoma with genome instability. Long non-coding RNAs (LncRNAs) have been functionally associated with genomic instability in cancers. However, the identification and prognostic value of lncRNAs related to genome instability have not been explored in hepatocellular carcinoma. In this study, we aim to identify a genomic instability-related lncRNA signature for predicting prognosis and the efficacy of immunotherapy in HCC patients., Methods: According to the somatic mutation and transcript data of 364 patients with HCC, we determined differentially expressed genome instability-related lncRNAs (GInLncRNAs). Gene ontology (GO) enrichment analyses and Kyoto Encyclopedia of genes and genomes enrichment analyses revealed the potential functions of genes co-expressed with those lncRNAs involved in cancer development and immune function. We further determined a genome instability-related lncRNA signature (GInLncSig) through Cox regression analysis and LASSO regression analysis. Thereafter, we performed correlation analyses with mutations, clinical stratification analyses, and survival analyses to evaluate GInLncSig predictive function. Subsequently, we construct a nomogram model for prognostic assessments of patients with HCC. Finally, we performed Immunocytes infiltration analysis, gene set enrichment analysis (ssGSEA) of immunity circle-associated pathways, and T cell-inflamed score to explore GInLncSig's potential value in guiding immunotherapy., Results: We identified 11 independent prognosis-associated GInLncRNAs (AC002511.2, LINC00501, LINC02055, LINC02714, LINC01508, LOC105371967, RP11_96A15.1, RP11_305F18.1, RP11_342M1.3, RP11_432J24.3, U95743.1) to construct a GInLncSig. According to the risk score calculated by GInLncSig, the high-risk group was characterized by a higher somatic mutation count, significantly poorer clinical prognosis, higher T cell-inflamed score, and specific tumor immune infiltration status compared to the low-risk group. Furthermore, we constructed a nomogram model to improve the reliability and clinical utility of predicting the prognosis of patients with HCC., Conclusion: Our study established a reliable prognostic prediction signature that could be a tool for prognosis prediction and a promising predictive biomarker of immunotherapy in hepatocellular carcinoma., (© 2022. Asian Pacific Association for the Study of the Liver.)

Purpose: We aimed to evaluate the safety and effectiveness of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) guided by multiple imaging modalities for hepatocellular carcinomas (HCCs) in special (i.e., high-risk or unfavorable) locations compared with those in conventional locations., Methods: A total of 122 HCC patients were enrolled, including 85 patients (69.7%) with HCC in conventional locations and 37 (30.3%) with HCC in special locations. The clinical data, overall survival (OS), progression-free survival (PFS), and procedure-related adverse events were analyzed., Results: RFA combined with TACE was successfully performed in all patients. Three complications (2.5%) occurred, with no significant difference between the conventional (n=1, 1.2%) and special (n=2, 5.4%) locations (P = 0.218). Complete tumor necrosis rate was not significantly different between the conventional (n=73, 85.9%) and special (n=34, 91.9%) locations at one-month imaging (P = 0.353). After a follow-up of 3-48 months, the PFS was 17 months for patients with HCC in conventional locations and 14 months for patients with HCC in special locations; one-year PFS rate was 68.1% in the conventional location group, not significantly (P = 0.741) different from 59.1% in the special location group. The OS was 28 months in the conventional location group while 32 months in the special location group. The cumulative one- and two-year OS rates were 89.9% and 63.3%, respectively, in the conventional location group, not significantly different from 96.3% and 65% in the special location group (P = 0.273). Age (P = 0.043) and tumor size (P < 0.001) were significant prognostic factors for OS, and tumor size (P < 0.001) was the only significant prognostic factor for PFS., Conclusion: RFA guided by multiple imaging modalities combined with TACE may be safe and effective for treating HCCs in special locations.

Background: Although a number of technical problems and donor safety issues associated with living donor liver transplantation (LDLT) have been resolved, some initial clinical studies showed an increased risk of hepatocellular carcinoma (HCC) recurrence in LDLT. This meta-analysis was conducted to assess differences in tumor recurrence between LDLT and deceased donor liver transplantation (DDLT)., Methods: After systematic retrievals of studies about LDLT and DDLT for HCC, articles were selected with a rationale of emphasizing inter-group comparability. Results from multivariate analyses were combined and discussed together with univariate analyses. In subgroup analysis, the impact of organ allocation policy was taken into consideration., Results: Seven articles were included in the meta-analysis. Overall, a salient result that emerged from the seven studies was a significant increased risk of HCC recurrence in the LDLT group than in the DDLT group (P = 0.01). The most significant increase in hazard ratio was found in studies where organs tended to be allocated to non-tumor patients., Conclusions: An increased risk for HCC recurrence in LDLT as compared with DDLT patients was found. The relatively shorter preoperative observation windows in LDLT may lead to fewer cases of HCC with invasive features being screened out, which may provide a possible explanation for the high rates of HCC recurrence.

Cripto-1 may act as an independent predictor for prognosis in hepatocellular carcinoma (HCC). However, the function of Cripto-1 in HCC cells and its response to postoperative transarterial chemoembolization (TACE) in HCC patients remains unclearly. Up-regulated Cripto-1 expression boosted the ability of cell proliferation, migration and invasion in HCC cells in vitro . While opposite results were observed in HCC cells with down-regulated Cripto-1 expression. Cripto-1 expression was correlated with epithelial-mesenchymal transition (EMT) relevant biomarkers. Furthermore, in high Cripto-1 expression patients, those with adjuvant TACE had favorable TTR and OS times. On contrary, adjuvant TACE may promote tumor recurrence but had no influence on OS time in patients with low Cripto-1 expression. In different subgroups of vascular invasion, larger tumor size or liver cirrhosis, patients with adjuvant TACE had longer TTR and OS times than those without TACE in patients with high Cripto-1 expression, while they could not obtain benefits from adjuvant TACE in patients with low-expressed Cripto-1 expression. In conclusion, Cripto-1 may be a potential prognostic factor in predicting outcome of HCC patients with TACE therapy, and combined with Cripto-1 and tumor features may be helpful to stratify patients with respect to prognosis and response to adjuvant TACE.

Background: Systemic chemotherapy is the major treatment modality for nasopharyngeal carcinoma (NPC) liver metastases. We investigated the effectiveness of radiofrequency ablation (RFA) treatment, which has not been well explored in this disease., Methods: One-hundred and thirty-four cases of NPC with liver metastases treated with chemotherapy, chemotherapy with RFA, or RFA alone were retrospectively analyzed. Patient survival was evaluated by the log-rank test. Survival was analyses using the Kaplan-Meier method. Cox multivariate analyses of clinicopathological features and different treatment approaches were conducted., Results: Local response rates were 58% in the RFA group, 78% in the chemotherapy group and 93% in the chemotherapy with RFA group (P < 0.001). Increased progression-free survival (PFS) and overall survival (OS) were observed in the chemotherapy with RFA group (P < 0.001). Cox multivariate analysis indicated that the number of liver metastases (1 vs. >1), the dimension of the largest liver metastases (≤3 cm vs. >3 cm), evaluation of treatment (response vs. no response) and disease-free survival (≤12 months vs. >12 months) were independent prognostic factors., Conclusions: RFA combined with chemotherapy is a promising treatment for NPC metastatic liver disease with improved local response, PFS, and OS compared to current chemotherapy protocols., (Copyright © 2012 Wiley Periodicals, Inc.)

Background & Objective: The prognosis of breast cancer patients with liver metastasis is poor. How to improve treatment efficacy and prolong survival of these patients is a challenge in clinic. This study was to explore the efficacy of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast cancer patients with liver metastasis, and analyze prognostic factors., Methods: Clinical data of 98 breast cancer patients with liver metastasis, treated from 1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. The prognostic factors correlated to clinical features and treatment approaches were determined using Cox multivariate model., Results: The total response rate was 45.9% for all patients, 48.6% for the 74 patients received systemic chemotherapy, 23.1% for the 13 patients received TACE, and 54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%, 19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months), and the progression-free survival was 6 months (0-50 months)., Conclusion: The combination of systemic chemotherapy and TACE may prolong the survival of breast cancer patients with liver metastasis.

Aim: To investigate whether Helicobacter species (Helicobacter spp.) could be detected in hepatocellular carcinoma (HCC) tissue., Methods: Liver samples from 28 patients with hepatocellular carcinoma (HCC) diagnosed by histopathology were studied. Twenty-two patients with other liver diseases (5 with liver trauma, 7 with cavernous liver hemangioma, 6 with liver cyst and 4 with hepatolithiasis), 25 patients with gastric cancer, 15 with colonic cancer and 15 with myoma of uterus served as controls. Two pieces of biopsy were obtained from each patient. One was cultured for Helicobacter spp. and extraction of DNA, the other was prepared for scanning electron microscopy (SEM) and in situ hybridization. The samples were cultured on Columbia agar plates with microaerobic techniques. Helicobacter spp. in biopsy from the studied subjects was detected by polymerase chain reaction (PCR) with Helicobacter spp. 16S rRNA primers. Amplified products were identified by Southern hybridization and sequenced further. Besides, other genes (vacA, cagA) specific for Helicobacter pylori (H pylori) were also detected by PCR. Helicobacter spp. in biopsies was observed by SEM. Transmission electron microscopy (TEM) was performed to identify the cultured positive Helicobacter spp. The presence of Helicobacter spp. was detected by in situ hybridization to confirm the type of Helicobacter., Results: The positive rate of Helicobacter cultured in HCC and gastric cancer tissue was 10.7% (3/28) and 24% (6/25), respectively. Helicobacter microorganisms were identified further by typical appearance on Gram staining, positive urease test and characteristic colony morphology on TEM. The bacterium was observed in adjacent hepatocytes of the two HCC samples by SEM. The number of cocci was greater than that of bacilli. The bacterium was also found in four gastric cancer samples. PCR showed that the positive rate of HCC and gastric cancer samples was 60.7% and 72% respectively, while the controls were negative (P<0.01). The PCR-amplified products were identified by Southern hybridization and sequenced. The homology to 16S rRNA of H pylori was 97.80%. The samples were verified by in situ hybridization for Helicobacter spp. 16S rRNA-mRNA and proved to be H pylori positive. There was no statistical significance between HCC and gastric cancer (P>0.05), but the positive rate of HCC and controls had statistical significance (P<0.01). Only 3 HCC samples and 2 gastric cancer samples of the cagA genes were detected. None of the samples reacted with primers for vacA in the two groups. As for the genotype of H pylori, type II had preference over type I., Conclusion: Helicobacter infection exists in liver tissues of HCC patients. Helicobacter spp. infection is related with HCC, which needs further research.

Objective: To investigate the relationship between Helicobacter species and primary liver carcinoma (PLC)., Methods: The liver samples resected during operation from 21 patients with PLC diagnosed by histopathology and 12 patients with other liver diseases as controls were studied. Helicobacter species in liver specimens from the studied subjects were examined by PCR with Helicobacter specific 16SrRNA primers. The amplified products were identified by Southern hybridization and nucleic acid hybridization in situ and sequencing. The specimens were made slices to undergo in situ hybridization of cDNA-mRNA of Helicobacter. Qualitative and quantitative studies were used to assess the correlation of liver tissue helicobacter infection with PLC., Results: Thirteen of the 21 samples (62%) of PLC were positive for Helicobacter specific 16SrRNA gene, while none was positive in the controls (P < 0.01). In situ hybridization results demonstrated a highly Helicobacter 16SrRNA-mRNA positive rate in the PLC group (62%) and none of positive specimen in the control group (P < 0.01). Nine of the Helicobacter specific PCR applicants were sequenced and a homology of 97.80% in comparison with 16SrRNA of H p was found., Conclusion: Helicobacter infection may exist in the liver tissues of PLC patients with a high infection rate, suggesting an association between Helicobacter infection and PLC.