Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer

Pandiyan Muthuramalingam; Sakthivel Akassh; Saravanan Bhavanisha Rithiga; Senthilkumar Prithika; Ravikumar Gunasekaran; Hyunsuk Shin; Reetesh Kumar; Venkidasamy Baskar; Jinwook Kim

doi:10.1016/j.ejphar.2022.175479

Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer

Eur J Pharmacol. 2023 Feb 5:940:175479. doi: 10.1016/j.ejphar.2022.175479. Epub 2022 Dec 21.

Authors

Pandiyan Muthuramalingam¹, Sakthivel Akassh², Saravanan Bhavanisha Rithiga², Senthilkumar Prithika², Ravikumar Gunasekaran², Hyunsuk Shin³, Reetesh Kumar⁴, Venkidasamy Baskar⁵, Jinwook Kim⁶

Affiliations

¹ Division of Horticultural Science, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, 52725, South Korea; Department of GreenBio Science, Gyeongsang National University, Jinju, 52725, South Korea; Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore, 641 062, India. Electronic address: pandianmuthuramalingam@gmail.com.
² Department of Biotechnology, Sri Shakthi Institute of Engineering and Technology, Coimbatore, 641 062, India.
³ Division of Horticultural Science, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, 52725, South Korea; Department of GreenBio Science, Gyeongsang National University, Jinju, 52725, South Korea. Electronic address: shinpomo@gnu.ac.kr.
⁴ Department of Agricultural Sciences, Institute of Applied Sciences & Humanities, GLA University, Mathura, 281 406, India.
⁵ Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, 600 077, India.
⁶ Division of Horticultural Science, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, 52725, South Korea; Department of GreenBio Science, Gyeongsang National University, Jinju, 52725, South Korea.

PMID: 36566006
DOI: 10.1016/j.ejphar.2022.175479

Abstract

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Keywords: Cheminformatics; Integrative omics; Lung cancer; Molecular docking; Network pharmacology; Phytocompounds.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Molecular Docking Simulation
Network Pharmacology
Pilot Projects
Prognosis