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Immunotherapy, including ICIs, has emerged as an invaluable treatment option for advanced PLC. Nevertheless, the expression patterns of PD‐L1 and PD‐1 in PLC remain incompletely understood. In this study, the expression pattern and clinical correlation of PD‐L1 and PD‐1 were analysed in 5245 PLC patients. The positivity rates of PD‐L1 and PD‐1 were very low in the patient PLCs, but the positivity rates of PD‐L1 and PD‐1 were higher in the ICC and cHCC‐ICC than in HCC. The expression of PD‐L1 and PD‐1 correlated with the malignant phenotypes and clinicopathological characteristics of PLC. Interestingly, PD‐1 positivity might serve as an independent prognostic factor. Based on a systematic analysis of a large amount of PLC tissues, we proposed a novel classification of PD‐1/PD‐L1 expression in HCC and ICC. In light of this stratification, we observed a close correlation between PD‐L1 levels and PD‐1 expression in HCC and ICC. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Complex genetic and epigenetic alterations are the two primary causes of HCC. The aim of the study was mainly to explore the correlation between the methylation status of DNAH17 and HCC. Methods: We evaluated the methylation levels of DNAH17 in 163 HCC samples and their paired normal tissue using Sequenom EpiTYPER assays and performed the TaqMan copy number assay to assess the copy number status of DNAH17 in HCC samples. Results: The mean methylation levels were significantly decreased in the tumor tissues compared to the paired normal tissues in both selected regions of DNAH17 (amplicon 1:58.7% vs 84.5%, P < 0.0001; amplicon 2:69.9% vs 84.5%, P = 0.0060). Contrarily，both RNA‐seq and immunohistochemistry indicated the expression of DNAH17 was increased in tumor tissues (P < 0.05). DNMT inhibitor decitabine treatment could increase the expression of DNAH17 in HCC cell lines. DNAH17 gene amplification always companied with hypomethylation status. Moreover, hypomethylation status was associated with several clinical characteristics, such as male patients, higher AFP values, higher age of onset, fibrous capsules, tumor necrosis, liver cirrhosis, and tumor thrombus (P < 0.05). Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of DNAH17 could efficiently predict the existence of the fibrous capsule (AUC = 0.695) and tumor thrombus (AUC = 0.806). Conclusions: These findings suggested that aberrant methylation of DNAH17 was associated with comprehensive HCC clinicopathological factors and could be a promising biomarker for tumor thrombosis in HCC patients. The aim of the study was to explore the correlation between the methylation status of DNAH17 and HCC. Our findings suggested that aberrant methylation of DNAH17 might contribute to hepatocarcinogenesis and progression and could be a promising biomarker for tumor thrombosis in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Currently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective., Objective: The aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC., Methods: We retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety., Results: We enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P<0.05). The ORRs of the chemo-regimen, dual-regimen, and triple-regimen groups were 18.2%, 55.5%, and 54.7%, respectively. The DCRs were 72.7%, 90%, and 96.2%, respectively, indicating significantly better outcomes in the combination therapy groups., Conclusion: The combination of chemotherapy with PD-1 inhibitors and lenvatinib demonstrates considerable efficacy and tolerability as a treatment strategy for patients with advanced ICC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dong, Sui, Lu, Guo, Duan, Wang, Geng, Dai and Yang.)

Substantial evidence indicates that transforming growth factor-beta 1 (TGF-β1) plays a vital role in epithelial-mesenchymal transition (EMT). PEG10 has been shown involved in invasion and metastasis of tumors. The present study investigated the role of PEG10 in TGF-β1-triggered EMT in hepatocellular carcinoma (HCC) progression. Immunohistochemistry and real-time PCR were used to measure the expression level of PEG10 in clinical HCC tissues with or without lymph node metastasis, and normal tissues. The results showed that PEG10 expression is higher in HCC tissues and associated with overall survival (OS) and lymph node metastasis. Moreover, PEG10 expression level was remarkably higher in hepatic cancer cells than the normal hepatic cell line L02. In the present study, we constructed an adenovirus vector containing the coding area of PEG10 (Ad-PEG10) and infected HepG2 cells and found that overexpression of PEG10 promoted the cell migration, invasion ability and EMT of HepG2 cells. TGF-β1 acted on HepG2 cells by enhancing cell migration, invasion, EMT and upregulating PEG10 expression level. However, cells pretreated with adenovirus vector of PEG10 shRNAs (Ad-shRNA1 and Ad-shRNA2) did not occur EMT prior to TGF-β1 stimulation. Moreover, TGF-β1 did not increase the migration and invasion of cells with PEG10 knockdown and overexpression of PEG10 confers chemoresistance to HepG2 cells. Accordingly, sufficient PEG10 expression level is essential for TGF-β1 induced EMT and associated with the chemoresistance in HepG2 cells.