TY - JOUR
T1 - Transcriptomic discovery of a theranostic signature (SERPINE1/MMP3/COL1A1/SPP1) for head and neck squamous cell carcinomas and identification of antrocinol as a candidate drug
AU - Shih, Ming Lang
AU - Lee, Jih Chin
AU - Cheng, Sheng Yao
AU - Lawal, Bashir
AU - Ho, Ching Liang
AU - Wu, Cheng Chia
AU - Tzeng, David T.W.
AU - Chen, Jia Hong
AU - Wu, Alexander T.H.
N1 - Funding Information:
Alexander T.H Wu was funded by grants from National Science and Technology Council, Taiwan 111-2314-B-038-142 and 111-2314-B-038 -098 Jih-Chin Lee was funded by TSGH-D-111060 and 110-2314-B-016-044-MY3 Jia-Hong Chen was funded by TSGH-C03-111030 Ching-Liang Ho was funded by TSGH-C02-111024.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/11
Y1 - 2022/11
N2 - Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC.
AB - Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC.
KW - Antrocinol
KW - Head and neck squamous cell carcinomas
KW - Theranostic biomarker discovery
KW - Transcriptomic analysis
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85140058895&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140058895&partnerID=8YFLogxK
U2 - 10.1016/j.compbiomed.2022.106185
DO - 10.1016/j.compbiomed.2022.106185
M3 - Article
AN - SCOPUS:85140058895
SN - 0010-4825
VL - 150
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
M1 - 106185
ER -
