Systematic analysis of the role and significance of target genes of active ingredients of traditional Chinese medicine injections in the progression and immune microenvironment of hepatocellular carcinoma

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Abstract

Background: Traditional Chinese medicine in China is an important adjuvant therapy for the treatment of hepatocellular carcinoma (HCC) and traditional Chinese medicines injections have a wide range of clinical applications. The purpose of this study was to identify the active ingredients and related genes of traditional Chinese medicine injections that can treat hepatocellular carcinoma.

Methods: Effective small molecule components were extracted from 14 types of traditional Chinese medicines from 8 injections and the main gene targets were identified. The 968 patients with HCC were classified based on the target gene set, and the characteristics of patients with different subtypes were analyzed. Patients with two subtypes of HCC were compared with normal tissues and cirrhosis to identify important gene targets related to traditional Chinese medicines in HCC progression.

Results: In this study, 138 important genes associated with traditional Chinese medicines were identified and two HCC subtypes were identified. By analyzing the differences between the two subtypes, 25 related genes were associated with HCC subtypes. Through clinical and pharmacological analysis, this study identified quercetin as an important traditional Chinese medicines small molecule and secreted phosphoprotein 1 (SPP1) as an important oncogene in HCC.

Conclusion: Traditional Chinese medicines injection is an important adjuvant treatment modality for HCC. SPP1 is an important oncogene in HCC.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Hepatocellular carcinoma

Josep Llovet, Robin Kate Kelley, Augusto Villanueva … (2021)

Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.

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Is Open Access

Immune checkpoint therapy in liver cancer

Feng Xu, Tianqiang Jin, Yuwen Zhu … (2018)

Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.

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Author and article information

Contributors

Chao Wang: URI : https://loop.frontiersin.org/people/2138796/overview

Jinbao Zhang: URI : https://loop.frontiersin.org/people/2094626/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 06 January 2023

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 1095965

Affiliations

[1] ¹ Department of General Surgery , First Affiliated Hospital of Dalian Medical University , Dalian, Liaoning, China

[2] ² Department of Dermatology , First Affiliated Hospital of Dalian Medical University , Dalian, Liaoning, China

[3] ³ Department of Plastic Surgery , First Affiliated Hospital of Dalian Medical University , Dalian, Liaoning, China

[4] ⁴ Department of Neurosurgery , First Affiliated Hospital of Dalian Medical University , Dalian, Liaoning, China

Author notes

Edited by: Zhi-qian Zhang, Southern University of Science and Technology, China

Reviewed by: Yongjun Guan, Renmin Hospital of Wuhan University, China

Weicheng Lu, Sun Yat-sen University Cancer Center (SYSUCC), China

Bole Tian, Sichuan University, China

*Correspondence: Jinbao Zhang, jinbaozhang1988@ 123456163.com

This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology

[ † ]

These authors have contributed equally to this work

Article

Publisher ID: 1095965

DOI: 10.3389/fphar.2022.1095965

PMC ID: 9852871

PubMed ID: 36686660

SO-VID: 0fae7c07-3a89-4025-a5b3-c795457f011c

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 11 November 2022

Date accepted : 14 December 2022

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Systematic analysis of the role and significance of target genes of active ingredients of traditional Chinese medicine injections in the progression and immune microenvironment of hepatocellular carcinoma

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Most cited references 30

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hepatocellular carcinoma

Immune checkpoint therapy in liver cancer

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