Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma.

Abstract

Background:

Oral cavity squamous cell carcinoma (OSCC) is an aggressive malignant tumor with high recurrence and poor prognosis in the advanced stage. Patient-derived xenografts (PDXs) serve as powerful preclinical platforms for drug testing and precision medicine for cancer therapy. We assess which molecular signatures affect tumor engraftment ability and tumor growth rate in OSCC PDXs.

Methods:

Treatment-naïve OSCC primary tumors were collected for PDX models establishment. Comprehensive genomic analysis, including whole-exome sequencing and RNA-seq, was performed on case-matched tumors and PDXs. Regulatory genes/pathways were analyzed to clarify which molecular signatures affect tumor engraftment ability and the tumor growth rate in OSCC PDXs.

Results:

Perineural invasion was found as an important pathological feature related to engraftment ability. Tumor microenvironment with enriched hypoxia, PI3K-Akt, and epithelial-mesenchymal transition pathways and decreased inflammatory responses had high engraftment ability and tumor growth rates in OSCC PDXs. High matrix metalloproteinase-1 (MMP1) expression was found that have a great graft advantage in xenografts and is associated with pooled disease-free survival in cancer patients.

Conclusion:

This study provides a panel with detailed genomic characteristics of OSCC PDXs, enabling preclinical studies on personalized therapy options for oral cancer. MMP1 could serve as a biomarker for predicting successful xenografts in OSCC patients.

• Authors: Wei-Chen Yen, Ian Yi-Feng Chang, Kai-Ping Chang, Chun-Nan Ouyang, Chiao-Rou Liu, Ting-Lin Tsai, Yi-Cheng Zhang, Chun-I Wang, Ya-Hui Wang, Alice L Yu, Hsuan Liu, Chih-Ching Wu, Yu-Sun Chang, Jau-Song Yu, Chia-Yu Yang
• Journal: Frontiers in oncology (Front Oncol) Vol. 12 Pg. 792297 ( 2022) ISSN: 2234-943X [Print] Switzerland
• PMID: 35444950 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Yen, Chang, Chang, Ouyang, Liu, Tsai, Zhang, Wang, Wang, Yu, Liu, Wu, Chang, Yu and Yang.