Electronic Journal of Liver Tumor

Assay for transposase-accessible chromatin using sequencing combined with RNA sequencing to explore the effect of helicase like transcription factor deletion on hepatocellular carcinoma

Zhang Yixuan, Ma Yarui, Wang Xiaobing, Jiao Yuchen

2023, 10(2): 7-15.

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Objective: To investigate the potential regulatory mechanism of helicase like transcription factor (HLTF) in hepatocellular carcinoma (HCC).
Method: HLTF was knockout through clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) in HCC cell line. RNA sequencing (RNA-seq) was applied to detect and analyze the differentially expressed genes of the wild type and HLTF knockout cells. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) was applied to detect the changes in chromatin accessibility of the wild type and HLTF knockout cells. The multi-omics analysis of RNA-seq and ATAC-seq was used to find the key signaling pathways and downstream genes of HLTF.
Result: The cancer genome atlas (TCGA) database analysis showed that HLTF was highly expressed in HCC and was associated with poor prognosis; RNA-seq sequencing showed that 563 genes were up-regulated and 656 genes were down-regulated in HLTF knockout cells compared to wild-type cells; ATAC-seq analysis showed a total of 27 818 regions had significantly altered in chromatin accessibility with HLTF deletion, including 14 225 regions with enhanced chromatin accessibility and 13 593 regions with weakened chromatin accessibility; motif enrichment analysis showed that Atf3, Fra1 and BATF were enriched in regions with enhanced chromatin accessibility, Fra1, Fra2 and JunB were enriched in regions with weakened chromatin accessibility; the combination of RNA-seq and ATAC-seq analysis showed that the overlapping genes were mainly enriched in the arachidonic acid metabolism pathway, Wnt signaling pathway, calcium signaling pathway and the transforming growth factor β (TGF-β) signaling pathway; the deletion of HLTF increased the expression of nuclear RNA export factor 3 (NXF3) and highly-expressed NXF3 was associated with better prognosis in HCC patients.
Conclusion: Our study pointed out that HLTF may be involved in regulating arachidonic acid metabolism pathway, Wnt signaling pathway, TGF-β signaling pathway, etc. NXF3 may be a potential downstream gene of HLTF, and our study provided directions and ideas to elucidate the mechanism of HLTF in HCC.

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

2023, 10(2): 16-26.

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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.

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

2023, 10(2): 27-32.

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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.

Research progress of autophagy in interventional therapy of primary hepatic carcinoma

Yu Chenxi, Yao Xuesong

2023, 10(2): 33-36.

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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.

Progress on the mechanism of lenvatinib resistance in hepatocellular carcinoma

Zhang Lisha, Kang Mingjia, Zhao Jian

2023, 10(2): 37-40.

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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.

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

2023, 10(2): 41-44.

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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.

Diagnosis of hilar cholangiocarcinoma and advances in the treatment of unresectable hilar cholangiocarcinoma

Yue Zipeng, Shi Baoqi

2023, 10(2): 45-50.

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Hilar cholangiocarcinoma (HCCA) has a high incidence in Asia, among which China has one of the highest morbidity and mortality. The early symptoms of HCCA are hidden and the clinical diagnosis is more difficult. Most of the patients are in the late stage and lose the opportunity of operation. For unresectable HCCA, the curative effect of different treatment methods is different. Based on some existing clinical trials, this paper reviews the diagnosis of HCCA and the treatment of unresectable HCCA, in order to provide reference for clinical diagnosis and treatment.

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

2023, 10(2): 51-54.

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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.

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