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Long-term outcomes of radiotherapy combined with immune checkpoint blockade inhibitor and lenvatinib therapy in hepatocellular carcinoma with portal vein tumor thrombus Zhao Ying, Li Kewei, Yang Yanmei, Li Wei, Li Guangxin, Li Gong Electronic Journal of Liver Tumor    2023, 10 (3): 58-63.   Abstract （306）      PDF （3346KB）（26）       Knowledge map    Save Objective:To explore the efficacy and safety of radiotherapy combined with immune checkpoint blockade inhibitor(PD-1 inhibitor) and lenvatinib in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Methods:Between March 2018 to October 2020, patients diagnosed with unresectable HCC with PVTT who were admitted to our hospital were screened. In whom we included patients who met Barcelona Clinic Liver Cancer (BCLC) stage C, with Vp3 or Vp4 type portal vein tumor thrombus, and had no prior systemic treatment. The primary endpoints were 3-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of PVTT. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. Results:47 patients were enrolled in the study, 39 of whom had Vp4 type PVTT. The median follow-up duration was 33.9 (range: 3.1-57.1) months. The median OS tuime was 11.9 (95%CI:7.5-16.3) months, and the 3-year OS rate was 18%. The median PFS tiume was 5 months(95%CI:3.5-6.5 months) , and the 3-year PFS rate was 10%. Among patients with Vp4 type PVTT, the median OS time was 9.4 months (95%CI:8.3-10.5 months) , and the 3-year OS rate was 13%. The median PFS time was 4.9 months (95%CI:3.2-6.6 months), and the 3-year PFS rate was 9%. The objective response rate of PVTT was 75%. No grade 3 or higher adverse events occurred. Conclusions:Radiotherapy combined with PD-1 inhibitor and lenvatinib in HCC patients with PVTT demonstrated favorable long-term efficacy and low toxicity. This triple combination therapy may become one of the competitive treatment options for HCC with BCLC stage C. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (4): 1-14.   Abstract （304）      PDF （2280KB）（267）       Knowledge map    Save Reference | Related Articles | Metrics

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Progress on the mechanism of lenvatinib resistance in hepatocellular carcinoma Zhang Lisha, Kang Mingjia, Zhao Jian Electronic Journal of Liver Tumor    2023, 10 (2): 37-40.   Abstract （213）      PDF （1635KB）（50）       Knowledge map    Save Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Lenvatinib is an inhibitor of multiple receptor tyrosine kinases, was approved in 2018 for the first-line treatment of unresectable HCC. However, the inevitable drug resistance of lenvatinib is the main reason that hindering its long-term anticancer activity, but the mechanism of drug resistance is not completely clear. In this paper, the potential mechanisms of resistance to lenvatinib in HCC were reviewed according to signal pathway and targets classification, providing reference for research on prevention or delay of lenvatinib resistance. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (3): 1-11.   Abstract （143）      PDF （1692KB）（255）       Knowledge map    Save Reference | Related Articles | Metrics

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Analysis of incidence and mortality of liver cancer in Shanxi cancer registries, 2019 Guo Xuerong, Cao Ling, Zhang Ruifeng, Wang Xinchen, Qiao Nan, Zhang Yongzhen Electronic Journal of Liver Tumor    2023, 10 (2): 27-32.   Abstract （141）      PDF （2308KB）（102）       Knowledge map    Save Objective: To analyze the incidence and mortality of liver cancer in Shanxi cancer registries in 2019, and to provide the strategies of prevention and treatment of liver cancer. Method: According to the "Chinese Guideline for Cancer Registration" and referring to the data quality audit evaluation standards formulated by the International Agency for Research on Cancer (IARC)/International Association of Cancer Registration (IACR), a summary analysis was conducted on the incidence, death, and population data of liver cancer reported by tumor registration points in Shanxi Province that meet the quality control standards. The incidence/mortality crude rate, standardized incidence/mortality rate, and the cumulative rate of 0-74 years old were calculated by gender, area (urban and rural), and age. The age-standardized of Chinese standard population (ASR China) and world standard population (ASR world) were calculated by the Chinese standard population in 2000 and Segi's population, respectively. Result: In 2019, 644 new cases of liver cancer were recorded in Shanxi cancer registries, accounting for 5.39% of all new cancer cases. The crude incidence rate was 13.18 per 100 000, with ASR China of 8.13 per 100 000 and ASR world of 8.30 per 100 000, respectively. The cumulative incidence rate (0-74 years old) was 0.96%. Liver cancer was the 7th most common cancer in the registration areas of China in 2019. The incidence of ASR China was 2.46 times in males as that in females, and it was 0.99 times in urban areas as that in rural areas. A total of 791 cases died of liver cancer in Shanxi cancer registries, accounting for 10.00% of all cancer deaths. The crude mortality rate was 16.19 per 100 000, with ASR China of 9.90 per 100 000 and ASR world of 10.06 per 100 000. The cumulative mortality rate (0-74 years old) was 1.16%. Liver cancer was the 4th most common cause of cancer deaths in the registration areas of China in 2019. The mortality of ASR China was 1.90 times in males as that in females, and it was 0.78 times in urban areas as that in rural areas. The incidence and mortality of liver cancer both increased with age, and the incidence increased more significantly after the age of 40. The incidence and mortality in Shanxi Province reached the peak in the age group of 85 years, and the male was higher than the female. Conclusion: The incidence and mortality rates of liver cancer in Shanxi cancer registries are lower than national average, the male is higher than the female, and higher in rural areas than in urban areas. Therefore, the prevention and treatment of liver cancer should focus on males and pelple in rural areas. Early diagnosis and treatment of liver cancer should be promoted to increase the detection rate of early liver cancer and reduce the disease burden caused by liver cancer. Reference | Related Articles | Metrics

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Analysis of the effect of mouthwash prepared with mannitol on tyrosine kinase receptor inhibitor oral mucosal adverse reactions in patients with liver cancer Wu Shu, Liu Yan, Zhan Zhengyin, Li Xiaoqing, Liu Zirong, Huang Lihui, Li Caiyun, Wang Jingya, Lu Hong Electronic Journal of Liver Tumor    2023, 10 (2): 51-54.   Abstract （122）      PDF （1833KB）（7）       Knowledge map    Save Objective: Tyrosine kinase transmembrane receptor inhibitors are widely used in the clinical treatment of liver cancer, and oral mucosal adverse reactions may occur. This study is to explore the effect of mannitol, lidocaine, dexamethasone and mouthwash in such patients. Method: In this paper, 46 patients with liver cancer who were treated with sorafenib, lenvatinib, regorafenib or cetuximab were selected as the research objects (all oral mask reactions were grade 2-3). They were randomly divided into 23 cases in the observation group and 23 cases in the control group. The control group used mannitol, lidocaine and dexamethasone to rinse the mouth when adverse reactions to the oral mask occurred, and the observation group was. Result: The effect of oral mucosal adverse reactions in the observation group was later than that in the control group and the symptoms were milder. The difference between the two groups was significant (P<0.05). Conclusion: The mannitol, lidocaine and dexamethasone preparation has a good effect on the oral mucosal side effects of the tyrosine kinase transmembrane receptor inhibitor, and it is worthy of clinical application. This article provides references for oncology nursing workers to deal with related adverse reactions. Reference | Related Articles | Metrics

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The progress of radiotherapy in hepatocellular carcinoma with portal vein tumor thrombus Xin Lingxia, Xu Xin, Zhai Yirui, Deng Min, Chen Bo Electronic Journal of Liver Tumor    2023, 10 (3): 76-82.   Abstract （114）      PDF （1746KB）（17）       Knowledge map    Save With a poor prognosis, hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) progresses rapidly and is life-threatening. Currently, the treatment options for HCC with PVTT mainly include transcatheter arterial intervention, radiotherapy, targeted therapy, immunotherapy, surgery, etc., but there is still no standard treatment strategy. Intensity-modulated radiotherapy can significantly raise the prescribed dose with the minimum dose delivery to the remaining liver, ensuring the safety of radiotherapy for HCC. Previous clinical studies have confirmed the safety and efficacy of radiotherapy for HCC with PVTT. With the deepening of the multidisciplinary treatment concept, radiotherapy combined with other treatments for HCC with PVTT has been continuously explored. Focusing on radiotherapy for HCC with PVTT, this review mainly discusses the progress of multidisciplinary combined therapy including radiotherapy, surgery, interventional therapy, targeted therapy, and immunotherapy. Reference | Related Articles | Metrics

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Research progress on the role of lysyl oxidase-like 2 in the development of hepatocellular carcinoma Shen Yaqiong, Li Jiao, Li Xingxin, Xu Jing, Jin Yan Electronic Journal of Liver Tumor    2023, 10 (2): 41-44.   Abstract （102）      PDF （2142KB）（9）       Knowledge map    Save Lysyl oxidase-like 2 (LOXL2), one of the members of the lysyl oxidase (LOX) family, can catalyze the covalent cross-linking of collagen and elastin in the extracellular matrix. It is found overexpressed in hepatocellular carcinoma (HCC) and can promote cell growth, tumor invasion and metastasis. In recent years, more and more evidences has showed that LOXL2 plays a key role in the occurrence and development of HCC. High level of LOXL2 is an independent factor affecting the prognosis of HCC, suggesting that it has great potential as therapeutic targets. Reference | Related Articles | Metrics

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Progress of vascular intervention combined with targeted therapy and immunotherapy for hepatocellular carcinoma Miao Jixuan, Jin Yong Electronic Journal of Liver Tumor    2023, 10 (3): 31-37.   Abstract （100）      PDF （1765KB）（25）       Knowledge map    Save Vascular interventional therapy represented by transcatheter arterial chemoembolization（TACE）and hepatic artery infusion chemotherapy is the main clinical treatment of unresectable hepatocellular carcinoma(HCC). Among them, TACE was used throughout the treatment of stage Ib to IIIb HCC. Targeted drugs such as multi-target tyrosine kinase inhibitors and angiogenesis inhibitors have played an important role in the treatment and adjuvant therapy of advanced liver cancer, and their clinical application has been quite mature. In recent years, immunotherapy led by immune checkpoint inhibitors has gradually become the latest hot spot in clinical research and application. Patients with high rates of HCC, most often found for the first time has been in the middle-late stage. For the treatment of such patients with HCC, existing vascular intervention targeted therapy and immunotherapy, a single treatment curative effect is not very desirable, this makes the combination therapy in treating HCC has become a new trend. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (2): 1-6.   Abstract （76）      PDF （5133KB）（29）       Knowledge map    Save Reference | Related Articles | Metrics

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Effect of narrative nursing model based on evidence-based medicine on early ambulation and compliance of patient Pan Wenbing, Lu Yao, Li Yan, Shi Zhuolin, Liu Yudi Electronic Journal of Liver Tumor    2023, 10 (3): 89-92.   Abstract （74）      PDF （1804KB）（52）       Knowledge map    Save Objective:To explore the effect of narrative nursing model based on evidence-based medicine on early ambulation and compliance of patients with primary liver cancer after transcatheter arterial chemoembolization (TACE). Methods:From December 2019 to February 2022, 70 patients with primary liver cancer undergoing TACE in our hospital were randomly divided into the control group (n=35) and the observation group (n=35) with conventional perioperative nursing and narrative nursing model based on evidence-based medicine. The early ambulation and early recovery, compliance before and after receiving nursing, quality of life score changes and postoperative complications were compared between the two groups. Results:The observation group had shorter first time out of bed activity and longer activity duration than the control group (P<0.05). The observation group had shorter anal exhaust, general food recovery, and hospitalization time in sequence compared to the control group (P<0.05). After nursing, the compliance and QLICP-LI scores of the observation group were higher than those of the control group (P<0.05). Compared with the control group, the observation group had a lower incidence of postoperative complications (P<0.05). Conclusion:The narrative nursing model based on evidence-based medicine for patients with primary liver cancer after TACE can shorten the time of early ambulation, promote postoperative recovery, reduce the occurrence of postoperative complications, improve patient compliance, and improve the quality of life. Reference | Related Articles | Metrics

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The global status and development trends of radioembolization for liver cancer with yttrium-90: a bibliometric analysis Tang Fan, Luo Yingen, Ou Aixin, Xu Haoran, Li Xiao Electronic Journal of Liver Tumor    2023, 10 (3): 38-47.   Abstract （72）      PDF （12361KB）（30）       Knowledge map    Save Objective:To investigate the global status and development trends of radioembolization for liver cancer with yttrium-90 through bibliometric analysis. Method:All available data of the articles concerning radioembolization for liver cancer with yttrium-90, based on Web of Science database from 1991 to 2021, were analyzed with bibliometric analysis for creating visual knowledge maps of the countries, institutions, authors, journals and keywords by VOS viewer. Result:According to the search strategy and screening criteria, a total of 989 articles related to radioembolization for liver cancer with yttrium-90 were included in this study, involving 4 406 researchers from 1 055 institutions in 47 countries. The overall number of annual and cumulative publications significantly showed an upward trend, reaching a peak in 2021. United States dominated in national cooperation and number of articles. The top three institutions of total publications were Northwestern University, University of Navarra and Washington University. The top three authors of total publications and citations were Salem R, Lewandowski RJ and Mulcahy MF. Journal of Vascular and Interventional Radiology and other journals have played a vital role in promoting the development of this field. The top 10 keywords with occurrence frequency were radioembolization, hepatocellular carcinoma, yttrium-90, Y-90 microspheres, survival, cancer, liver metastases, microspheres, selective internal radiation therapy and internal radiation therapy. Conclusion:Radioembolization for liver cancer with yttrium-90 is one of the important research hotspots of liver cancer. Chinese researchers should not only pay attention to the frontier research in this field, but also actively carry out multicenter clinical research projects. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (2): 55-58.   Abstract （65）      PDF （3951KB）（12）       Knowledge map    Save Related Articles | Metrics

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Research progress of autophagy in interventional therapy of primary hepatic carcinoma Yu Chenxi, Yao Xuesong Electronic Journal of Liver Tumor    2023, 10 (2): 33-36.   Abstract （60）      PDF （1755KB）（18）       Knowledge map    Save Primary hepatic carcinoma is one of most common malignant tumors in China. Interventional therapy plays an important role in primary hepatic carcinoma, suitable for Ia-IIIb stage patients according to China liver cancer staging (CNLC). As a metabolic process unique to eukaryotic cells, autophagy is involved in metabolic diseases and malignant tumors, and plays an important role in the tumorigenesis of primary hepatic carcinoma, especially promoting the tolerance of tumor cells to interventional therapy, which makes the treatment ineffective. In this paper, we review the effects of common interventional treatments for primary hepatic carcinoma on autophagy in tumor cells. Ablation therapy, transvascular interventional therapy, and internal radiation therapy can promote levels of autophagy in tumor cells by cellular pathways such as hypoxia inducible factor-1α (HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), resulting in treatment resistance. In vitro studies, the use of autophagy inhibitors has prevent therapeutic resistance from autophagy. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (3): 12-26.   Abstract （59）      PDF （3747KB）（38）       Knowledge map    Save Reference | Related Articles | Metrics

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Effect of aryl hydrocarbon receptor gene knockout on metabolic pathways and metabolites in hepatocellular carcinoma Wei Zhewen, Zhu Qing, Cai Jianqiang Electronic Journal of Liver Tumor    2023, 10 (4): 23-28.   Abstract （59）      PDF （4069KB）（12）       Knowledge map    Save Objective:To investigate the effect of aryl hydrocarbon receptor (AHR) gene knockout on metabolic pathways and metabolites in hepatocellular carcinoma (HCC). Method:PLC/PRF/5 hepatoma cell line with AHR knockout was constructed by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. Untargeted metabolomics was performed on the wild type (AHR-WT) and AHR knockout (AHR-KO) hepatoma cells to detect the metabolites, and the differential metabolites between the two groups were analyzed. Metaboanalyst 4.0 was used to perform metabolic pathway enrichment analysis and find differential metabolites. Result:The AHR-WT and AHR-KO hepatoma cells were examined for metabolites under positive and negative ionic model respectively. The results showed that the top 10 functional enrichments were mainly amino acid metabolism glutamate metabolism, glycine and serine metabolism, arginine and proline metabolism, methionine metabolism, aspartate metabolism, urea cycle, ammonia recycling, energy metabolism glutathione metabolism, Warburg effect and nucleotide metabolism purine metabolism. The pathway enrichment analysis showed that eight metabolic pathways were found including arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, alanine, aspartic acid and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, purine metabolism, lysine degradation, ascorbic acid and uronate metabolism. Compared with AHR-WT hepatoma cells, the levels of L-arginine, L-phenylalanine, L-tyrosine, uridine and xanthine were significantly down-regulated in AHR-KO hepatoma cells. Nicotinamide adenine dinucleotide (NADH), oxidized glutathione and nicotinamide adenine dinucleotide phosphate (NADPH) were significantly up-regulated in the AHR-KO cells. Conclusion:AHR may play an important role in the metabolism of HCC, and the research on the metabonomics of HCC by targeting AHR may be a new anti-tumor treatment strategy. Reference | Related Articles | Metrics

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Electronic Journal of Liver Tumor    2023, 10 (3): 104-105.   Abstract （58）      PDF （1994KB）（35）       Knowledge map    Save Related Articles | Metrics

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Recognition of bone metastasis driving genes in hepatocellular carcinoma by machine learning and analysis of in external-beam radiotherapy Wang Yu, Tong Liexing, Kang Wanying, Ding Xin, Qian Hesheng Electronic Journal of Liver Tumor    2023, 10 (3): 64-75.   Abstract （55）      PDF （6518KB）（6）       Knowledge map    Save Objective:To identify the driving genes of hepatocellular carcinoma with bone metastasis (HCC-BM) by machine learning and to explore the effect of external-beam radiotherapy (EBRT) on the expression level of driving genes. Methods:GSE14520 and GSE84402 data sets in Gene Expression Omnibus database were combined as test sets, and GSE121248 andGSE54236 data sets were used as validation sets respectively. The least absolute shrinkage and selection operator and support vector machine-regression feature elimination were performed to screen the key differentially expressed genes,and the intersection with HCC-BM related genes in the GeneCards database obtained HCC-BM driving genes. CIBERSORT evaluated the correlation between HCC-BM driver gene and immune cell infiltration.The 22 HCC-BM patients admitted to our hospital from 2020 to 2021 were selected as the study group. In the same period, 22 healthy people with normal physical examinations in our hospital were selected as the control group. The changes in HCC-BM driver gene expression before and after EBRT were compared, and the relationship between HCC-BM driver gene expression and and relationship with ASPM expression levels and pain relief. Results:Four HCC-BM driving genes were identified,it is respectively assembly factor for spindle microtubules (ASPM), C-type lectin domain family 4 member M (CLEC4M), extracellular matrix protein 1 (ECM1), and ficolin 2 (FCN2). The expression of ASPM in normal liver tissue was lower than that in HCC tissue (P<0.05), and the expression of clec4m, ECM1, and FCN2 was higher than that in HCC tissue (P<0.05). The same results were obtained in both validation sets GSE121248 and GSE54236. The prognosis of HCC patients with high ASPM expression is poor, while patients with low CLEC4M, ECM1 and FCN2 expression are better. ASPM was positively correlated with macrophages m2; CLEC4M was positively correlated with macrophages M2, neutrophils, and M1 macrophages; FCN2 was negatively correlated with macrophages M0. The expression of serum ASPM in 22 patients with HCC-BM was higher than that in the healthy control group (P < 0.05), and the expression of FCN2 was lower than that in the healthy control group (P<0.05). After EBRT, the expression level of serum ASPM in HCC-BM patients decreased (P<0.05). The expression level of serum ASPM in patients with complete remission was lower than that in patients with partial remission. Conclusions:ASPM, CLEC4M, ECM1, and FCN2 may be involved in the pathogenesis of HCC-BM. Among them, ASPM may be related to the effect of EBRT. Further exploration of driver genes is helpful to develop therapeutic targets, improve the effect of EBRT and then improve the prognosis. Reference | Related Articles | Metrics

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Involvement of microRNA-551a in the response mechanism of sorafenib in patients with advanced hepatocellular carcinoma Bian Tao, Qin Feng, Wang Shengjie, Wang Hui, Han Shanshan Electronic Journal of Liver Tumor    2023, 10 (2): 16-26.   Abstract （55）      PDF （10919KB）（12）       Knowledge map    Save Objective: Sorafenib is one of the standard first-line therapies for patients with advanced hepatocellular carcinoma (HCC) disease. This study aimed to explore the role of microRNAs (miRNAs) in sorafenib response mechanisms. Method: HCC-related miRNAs expression profiles were analyzed, and a comprehensive bioinformatics approach identified sorafenib response miRNAs and their associated molecular mechanisms. A total of 24 patients with advanced HCC admitted to our hospital for treatment between February 2021 and February 2022 were selected. During the same period, 18 patients with cirrhosis admitted for treatment were selected as the control group. To verify the expression characteristics and prognostic value of sorafenib-responsive miRNAs. Result: HCC patients with high miRNA-551a expression had a poorer prognosis, and expression was suppressed by sorafenib, which is involved in HCC progression and sorafenib response mechanisms through multiple pro-oncogenic pathways and autophagic pathways. In the clinical validation cohort, serum miRNA-551a expression was higher in advanced HCC patients before sorafenib treatment than in controls (P<0.05) and decreased after treatment (P<0.05). Patients with advanced HCC with high pre-treatment serum miRNA-551a expression benefited from sorafenib treatment (P<0.05). Univariate and multivariate Cox proportional regression models also confirmed that pre-treatment serum miRNA-551a levels could predict the prognosis of advanced HCC patients treated with sorafenib independently of clinicopathological features (P<0.05). Molecular docking and kinetic modeling confirmed that sorafenib directly binds pre-miRNA-551a and prevents cleavage of pre-miRNA-551a from maturing miRNA-551a by the endoribonuclease Dicer. The Nomogram model based on the combination of miRNA-551a expression characteristics and clinicopathological features effectively predicted the prognosis of HCC patients at survival rates at 1-, 3- and 5- years and, ideally, screening of sorafenib-responsive patients. Conclusion: miRNA-551a, as a pro-oncogene, can be suppressed by sorafenib expression involved in its response mechanism. The assessment and targeting of miRNA-551a expression characteristics can help personalize the treatment of HCC patients. Reference | Related Articles | Metrics

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Research progress of driver gene alteration and targeted therapy for intrahepatic cholangiocarcinoma Zhang Shihui, Li Zhuo, Yihebali·Chi, Shi Susheng Electronic Journal of Liver Tumor    2023, 10 (4): 15-22.   Abstract （54）      PDF （1810KB）（19）       Knowledge map    Save Intrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer originating from the intrahepatic bile duct epithelium, which is second only to hepatocellular carcinoma in terms of incidence and is extremely malignant with a 5-year overall survival rate of less than 10%. Surgery is the perferred radical treatment choice. Patients with advanced disease are resistant to radiotherapy or chemotherapy, the efficacy is unsatisfactory, and there is an urgent need to find new and effective treatment methods. With the advent of precision medicine, research on the mechanisms of multiple driver gene alterations and signaling pathway abnormalities in intrahepatic cholangiocarcinoma in China and abroad has been intensifying in recent years, and targeted therapy and immunotherapy have been more and more widely used in clinical practice. This paper is intended to review the research progress of driver gene alterations and targeted therapies for intrahepatic cholangiocarcinoma. Reference | Related Articles | Metrics