Table of Content

30 September 2024, Volume 11 Issue 3

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A new strategy for solid tumor treatment: the immunotherapeutic potential of chimeric antigen receptor macrophages

Kong Qinghao, Li Shuang, Lu Yinying

2024, 11(3):  16-19. 

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Solid tumors are one of the major diseases threatening human health worldwide. Traditional treatments such as surgery, radiotherapy, and chemotherapy have their inherent limitations, and although immune checkpoint inhibitors have shown efficacy, not all patients respond to them. Chimeric antigen receptor-macrophage (CAR-M) therapy involves the genetic engineering of macrophages to express chimeric receptors that specifically recognize tumor antigens, demonstrating the potential for targeted tumor cell destruction. However, CAR-M therapy for solid tumors is currently in the preclinical and early clinical research stages. This paper provides a comprehensive review of the current state of preclinical studies on CAR-M, including the design of CAR structures, sources of donor cells, and vectors for delivering CAR genes to macrophages. Additionally, it summarizes the limitations and challenges faced in the development of CAR-M, offering new research perspectives for the future advancement of CAR-M therapy.

Preliminary observe of the efficacy and safety of mixed liver cancer immunotherapy

Liang Jun, Yang Zhenyun, Zhang Yaojun, Chen Minshan, Hu Dandan

2024, 11(3):  20-24. 

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Objective: To observe preliminary the efficacy and safety of immune checkpoint inhibitors in the treatment of mixed liver cancer.
Methods: From January 2018 to December 2023, clinical data of patients admitted to the Cancer Prevention Center of Sun Yat-sen University were collected, including basic information, treatment plan, laboratory indicators and survival status. Efficacy was assessed by response evaluation criteria in solid tumors v1.1 for solid tumors. The survival analysis with Kaplan-Meier curve. The univariate and multivariate analysis with Cox regression model.
Results: A total of 21 patients with mixed liver cancer were collected. The median age was 55 years. The objective response rate was 28.6%. The disease control rate was 52.4%. The median progression-free survival time was 12.4 months (95%CI : 6.7-18.1 months). The median overall survival time was 14.4 months (95%CI: 10.4-18.4 months). Multivariate analysis showed that cancer thrombus (HR=3.95, 95%CI: 1.09-14.28, P=0.036) and increased carcinoembryonic antigen levels (>5 μg/L) (HR=5.46, 95%CI: 1.14-26.17, P=0.034) were associated with poor progression-free survival time. Adverse events of any level were controllable and no adverse event-related deaths.
Conclusion: Preliminary observe shows that the immune checkpoint inhibitors have good efficacy and safety in the treatment of mixed liver cancer, and the increased thrombus and increased antigen level (> 5 μg/L) may be adverse factors to shorten the progression-free survival time.

Clinical features and prognosis analysis of combined mixed hepatocellular carcinoma, hepatocellular carcinoma and intrahepatic cholangiocarcinoma after surgical resection: propensity match analysis

Zhu Runze, Mu Shaowei, Li Zhao, Zhu Jiye, Gao Jie

2024, 11(3):  25-32. 

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Objective: To compare the clinicopathological features and prognosis of mixed hepatocellular carcinoma (mHCC), hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) after surgical resection.
Methods: The clinical data of 317 patients diagnosed with liver malignant tumors who were admitted to the Department of Hepatobiliary Surgery, Peking University People's Hospital from January 2015 to December 2023 were retrospectively analyzed. After propensity matching with 1:1 in the degree of tumor differentiation, lymph node metastasis and AJCC (8th edition) stage, 150 patients were enrolled in two independent matching cohorts: mHCC and HCC 43 cases each, mHCC and ICC 32 cases each. The clinical characteristics and prognosis of patients were compared between groups. Normally distributed continuous variables were compared using Student's t-test or one-way ANOVA, and non-normally distributed continuous variables were compared using Wilcoxon rank sum statistics. Chi-square test is used to compare categorical variables. The Kaplan-Meier method assesses median survival and median disease-free survival.
Results: The age, sex, and degree of cirrhosis of mHCC patients were similar to those of HCC and ICC patients, and the prevalence of hepatitis B was lower than that of HCC patients but comparable to that of ICC patients. mHCC patients had significantly higher levels of AFP than those of ICC patients, lower levels of CA19-9 than those of HCC patients, and significantly higher levels of CEA than those of the other two pathological types. mHCC's pathological features of microvascular invasion rate and lymph node metastasis rate were higher than those of HCC and comparable to those of ICC.The median survival of mHCC patients was worse than that of HCC patients (19.6 months vs. 70.8 months, P<0.001) and comparable to that of ICC patients (19.6 months vs. 40.6 months, P=0.07). mHCC patients had a worse disease-free survival than that of HCC patients and comparable to that of ICC patients. Multifactorial Cox analysis showed that lymph node metastasis, poorly differentiated tumor, tumor stage, pathological type and history of alcohol consumption were independent risk factors associated with prognosis, and that poorly differentiated tumor and tumor stage were independent risk factors for disease-free survival; multiple tumors were an independent risk factor affecting postoperative prognosis in both 1:1 matched cohorts.
Conclusions: The clinical features and prognosis of mHCC are not consistent with those of HCC and ICC, and it is a rare pathological type with a high degree of malignancy that is highly susceptible to recurrence, and it should be treated as a unique tumor type in primary hepatocellular carcinoma. The mHCC has a poorer long-term survival than HCC, and it is comparable to that of ICC, and lymph node metastasis, poorly differentiated tumors, tumor stage, and a history of alcohol consumption are prognostically relevant independent risk factors, luminal surgery was a prognostically relevant independent insurance factor, and poorly differentiated tumors and tumor stage were independent risk factors for disease-free survival. The multiple tumors were found to be associated with poor prognosis and recurrent metastases in mHCC after propensity matching.

Expression and clinical significance of transmembrane protein 132A in liver cancer based on bioinformatics

Zhao Hangqi, Ma Xiaowen, Zhang Tian'ai, Li Baifeng

2024, 11(3):  33-41. 

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Objective: To explore the expression pattern and clinical significance of transmembrane protein 132A (TMEM132A) in liver cancer based on public databases.
Methods: The Cancer Genome Atlas and GSE14520, GSE60502 of Gene Expression Omnibus was used to analyze the mRNA level of TMEM132A in liver cancer and adjacent tissues, the promoter methylation level, and the correlation with clinical factors. The immunohistochemical results of TMEM132A in tissues were obtained through HPA database. Kaplan-Meier method was used to explore the correlation between TMEM132A and the prognosis of patients. Receiver operating characteristic curve was used to explore whether TMEM132A could accurately diagnose patients. The drug sensitivity of TMEM132A to chemotherapy drugs was predicted by cancer drug sensitivity genomics. Immune analysis of TEME132A was performed by single-sample GSEA, TIMER, STORMAL SCORE and immune checkpoint heatmap. Linkedomics website was used to perform gene set enrichment analysis for differential genes of TMEM132A. The STRING database was used to predict the interacting proteins of TMEM132A.
Results: The expression of MEM132A in HCC tissues was significantly higher than that in adjacent tissues (P<0.05), and it was located in the cytoplasm and cell membrane. The high expression of TMEM132A was positively correlated with tumor stage, grade, AFP level and body weight. High expression of TMEM132A indicates poor prognosis and can be used as an accurate diagnostic indicator. TMEM132A is sensitive to a variety of chemotherapy drugs and infiltrated by a variety of immune cells, which can be used as a research target for drug therapy and immunotherapy. The promoter methylation level of TMEM132 was significantly decreased in cancer tissues. TMEM132A affects cell adhesion, fatty acid metabolism and other signaling pathways.
Conclusion: TMEM132A is highly expressed in HCC and positively correlated with poor prognosis.

Intraoperative use of dexmedetomidine in patients with hepatocellular carcinoma: prognostic impact and mechanism analysis

Shao Chaoyan, Ma Zhonglin, Wu Wei, Wu Song, Zheng Lidong

2024, 11(3):  42-53. 

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Objective: The aim is to investigate the impact of intraoperative dexmedetomidine (DEX) on the prognosis of patients with hepatocellular carcinoma (HCC) and to investigate the underlying mechanisms.
Methods: Retrospective analysis of clinical data of 144 HCC patients undergoing hepatectomy in Lu’an Hospital of Anhui Medical University from January 2019 to January 2023. The association between DEX and the prognosis of HCC patients was determined by univariate and multifactorial Cox risk regression. To resolve DEX cancer-promoting mechanisms by bioinformatics, western blotting, immunohistochemistry and various online databases.
Results: 144 patients were followed up for 6-48 months with a mean follow-up time of 32.9 months, including 63 recurred and 57 patients died. Patients with intraoperative DEX had lower recurrence-free survival (P<0.05) and overall survival (P<0.05) than those without DEX. Univariate combined with multifactorial Cox risk regression analysis identified intraoperative DEX use as an independent risk factor for recurrence and death in HCC patients (P<0.05). Six DEX-regulated genes were identified based on the GSE188867 dataset and the TCGA-HCC cohort: CCDC34, E2F8, CENPH, CTHRC1, CENPW, and E2F1. Western blotting and IHC results showed that E2F8 and E2F1 expression was increased in HCC tissues (P<0.05) and was rapidly upregulated by DEX (P<0.05). Computerized molecular docking models showed that DEX stably formed hydrogen bonds with ARC-267 and LYS-264 residues in E2F8 at a binding energy of -6.7 kcal/mol and with TYR-746 residues in E2F1 at an energy of -5.0 kcal/mol. The results of gene set enrichment analysis (GSEA) highlighted that DEX could rapidly activate cell cycle signaling (P<0.05).
Conclusion: Intraoperative systemic administration of DEX mediates a worse prognosis in patients with HCC, a process that involves DEX's rapid activation of cell cycle signaling, including possible direct binding to E2F8 and E2F1. DEX should be used with caution in patients with HCC.

Study on the development trend of liver cancer mortality among Chinese residents from 2012 to 2021

Shao Tang, Zheng Fangshu, Wu Jun

2024, 11(3):  54-57. 

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Objective: To analyze the trends of liver cancer mortality and standardized mortality among Chinese residents from 2012 to 2021.
Methods: The trend of liver cancer mortality and standardized mortality among Chinese residents was studied and analyzed by using the Joinpoint regression model with the number of liver cancer deaths and survey population in the National Disease Surveillance System Cause of Death Surveillance Dataset (2012), the Chinese Cause of Death Surveillance Dataset (2013-2021), and the data from the 6th and 7th national census as the study data.
Results: The number of liver cancer deaths and mortality rates among men in the surveillance population from 2012 to 2021 years were approximately 2.7 to 2.8 times higher than those among women. There were 2 Joinpoint turning points for liver cancer mortality in the total, male and female populations in the surveillance population from 2012 to 2021 years, with the turning points in the male population occurring in 2014 years and 2018 years, with an increasing trend from 2012 to 2014 years (P<0.05) and a decreasing trend from 2014 to 2018 years (P<0.05). The turning points in the total and female populations occurred in 2014 years and 2019 years, with an upward trend from 2012 to 2014 years (P<0.05) and a downward trend from 2014 to 2019 years (P<0.05). There was one Joinpoint turning point of liver cancer mortality in the total population, male population and female population, which occurred in 2019 years, and the female population showed an increasing trend from 2019 to 2021 years (P<0.05).
Conclusion: The mortality rate of liver cancer in the monitored population was higher in males than in females, and its development trend showed an increasing trend before 2014 and a decreasing trend after 2014, and the trend of the standardized mortality rate of liver cancer tended to be stable.

From susceptibility to prognosis: the multifaceted role of the cytochrome p450 family in hepatocellular carcinoma

Hong Shengjie, Zhang Guangquan, Li Ruixi, He Yongfei, Wu Fenfang, Shi Xianjie

2024, 11(3):  58-63. 

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The cytochrome P450 (CYP450) family is a group of enzymes that play a crucial role in the metabolism of exogenous and endogenous compounds. Growing evidence suggests that the CYP450 family is pivotal in the occurrence, progression, and prognosis of hepatocellular carcinoma (HCC). Polymorphisms in CYP450 family genes can influence an individual's susceptibility to carcinogens and metabolic capacity, closely associated with the risk of HCC. Furthermore, dysregulation of CYP450 family genes is involved in HCC progression, with mechanisms encompassing reactive oxygen species levels, DNA damage, cell proliferation, invasion, and apoptosis. The expression levels of CYP450 family genes are also intimately linked to the prognosis of HCC patients, showing promise as essential indicators for prognostic assessment. In conclusion, a deep understanding of the role of the CYP450 family in the occurrence, progression, and prognosis of HCC is of great significance for elucidating the molecular mechanisms of HCC and developing individualized prevention and treatment strategies. Future research should further investigate the molecular mechanisms underlying the polymorphisms and dysregulation of CYP450 family genes, establish corresponding risk prediction and prognostic evaluation models, and emphasize the regulatory effects of drugs on the CYP450 family, aiming to provide new strategies and targets for the prevention and treatment of HCC.