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Network pharmacology-based and clinically relevant prediction of active ingredients and potential targets of Chinese herbs on stage IV lung adenocarcinoma patients

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Aim

This study is designed to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV lung adenocarcinoma based on clinical data and network pharmacology. In addition, we showed that Chinese Herbal Medicine (CHM) treatment was associated with survival benefit for patients with stage IV lung adenocarcinoma and identified 18 herbs beneficial to survival through correlation analysis.

Background

Increasing evidence has shown that CHM has efficient therapeutic effects for advanced lung adenocarcinoma, while active ingredients and potential targets remain unclear.

Methods

Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was used to decipher the potential therapeutic mechanisms of CHM.

Results

CHM treatment was an independent protective factor. The hazard ratio (HR) was 0.487 (95% CI 0.293–0.807; P = 0.005). Patients in the CHM group had a longer median survival time (31 months) compared with the non-CHM group (19 months; P < 0.001). 18 out of the total 241 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analysis suggested that the 18 herbs realize anti-lung-adenocarcinoma activity mainly through (1) inhibiting the activity of some growth factors’ receptors, such as HGFR, EGFR, and IGFR. (2) Suppressing angiogenesis not only through VEGFR and PDGFR, but also through the function of neurotransmitters such as dopamine and serotonin. (3) Inhibiting the Ras signaling pathway directly through Ras as well as through ALK and FNTA/FNTB.

Conclusions

We performed a network pharmacological method to decipher the underlying mechanisms, which provides a good foundation for herbal research based on clinical data.

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Acknowledgements

The National Science Foundation of China (81903934) supported this work.

Author information

Author notes

  1. Jinfeng Liu and Jian Hao have contributed equally to this study and share first authorship.

Authors and Affiliations

  1. Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He-Xi District, Tianjin, 300060, China

    Jinfeng Liu & Xiongzhi Wu

  2. Department of Rheumatology, Tianjin Medical University General Hospital, Tianjin, China

    Jian Hao

  3. Tianjin Children’s Hospital, Tianjin, 300134, China

    Yangyang Niu

  4. Cancer Center, Tianjin Nankai Hospital, Tianjin, China

    Xiongzhi Wu

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  1. Jinfeng Liu
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  2. Jian Hao
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  4. Xiongzhi Wu
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Correspondence to Xiongzhi Wu.

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Liu, J., Hao, J., Niu, Y. et al. Network pharmacology-based and clinically relevant prediction of active ingredients and potential targets of Chinese herbs on stage IV lung adenocarcinoma patients. J Cancer Res Clin Oncol 147, 2079–2092 (2021). https://doi.org/10.1007/s00432-020-03488-0

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