Therapeutic implications of transcriptomics in head and neck cancer patient-derived xenografts

被引:3
|
作者
Lee, Rex H. [1 ]
Roy, Ritu [2 ]
Li, Hua [1 ]
Hechmer, Aaron [2 ]
Zhu, Tian Ran [1 ]
Izgutdina, Adila [1 ]
Olshen, Adam B. [2 ,3 ]
Johnson, Daniel E. [1 ]
Grandis, Jennifer R. [1 ]
机构
[1] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA
[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA
来源
PLOS ONE | 2023年 / 18卷 / 03期
基金
美国国家卫生研究院;
关键词
HUMAN-PAPILLOMAVIRUS; REPAIR; HPV;
D O I
10.1371/journal.pone.0282177
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
There are currently no clinical strategies utilizing tumor gene expression to inform therapeutic selection for patients with head and neck squamous cell carcinoma (HNSCC). One of the challenges in developing predictive biomarkers is the limited characterization of preclinical HNSCC models. Patient-derived xenografts (PDXs) are increasingly recognized as translationally relevant preclinical avatars for human tumors; however, the overall transcriptomic concordance of HNSCC PDXs with primary human HNSCC is understudied, especially in human papillomavirus-associated (HPV+) disease. Here, we characterized 64 HNSCC PDXs (16 HPV+ and 48 HPV-) at the transcriptomic level using RNA-sequencing. The range of human-specific reads per PDX varied from 64.6%-96.5%, with a comparison of the most differentially expressed genes before and after removal of mouse transcripts revealing no significant benefit to filtering out mouse mRNA reads in this cohort. We demonstrate that four previously established HNSCC molecular subtypes found in The Cancer Genome Atlas (TCGA) are also clearly recapitulated in HNSCC PDXs. Unsupervised hierarchical clustering yielded a striking natural division of HNSCC PDXs by HPV status, with C19orf57 (BRME1), a gene previously correlated with positive response to cisplatin in cervical cancer, among the most significantly differentially expressed genes between HPV+ and HPV- PDXs. In vivo experiments demonstrated a possible relationship between increased C19orf57 expression and superior anti-tumor responses of PDXs to cisplatin, which should be investigated further. These findings highlight the value of PDXs as models for HPV+ and HPV- HNSCC, providing a resource for future discovery of predictive biomarkers to guide treatment selection in HNSCC.
引用
收藏
页数:18
相关论文
共 50 条
  • [1] Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts
    Li, Hua
    Wheeler, Sarah
    Park, Yongseok
    Ju, Zhenlin
    Thomas, Sufi M.
    Fichera, Michele
    Egloff, Ann M.
    Lui, Vivian W.
    Duvvuri, Umamaheswar
    Bauman, Julie E.
    Mills, Gordon B.
    Grandis, Jennifer R.
    MOLECULAR CANCER RESEARCH, 2016, 14 (03) : 278 - 286
  • [2] Patient-derived xenografts of head and neck cancer - establishment & biomarker evaluation
    Klinghammer, K.
    Raguse, J. D.
    Plath, T.
    Wulf-Goldenberg, A.
    Keilholz, U.
    Hoffmann, J.
    Fichtner, I
    ONKOLOGIE, 2013, 36 : 93 - 94
  • [3] Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
    Kang, Han Na
    Kim, Jae-Hwan
    Park, A-Young
    Choi, Jae Woo
    Lim, Sun Min
    Kim, Jinna
    Shin, Eun Joo
    Hong, Min Hee
    Pyo, Kyoung-Ho
    Yun, Mi Ran
    Kim, Dong Hwi
    Lee, Hanna
    Yoon, Sun Och
    Kim, Da Hee
    Park, Young Min
    Byeon, Hyung Kwon
    Jung, Inkyung
    Paik, Soonmyung
    Koh, Yoon Woo
    Cho, Byoung Chul
    Kim, Hye Ryun
    BMC CANCER, 2020, 20 (01)
  • [4] Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
    Han Na Kang
    Jae-Hwan Kim
    A-Young Park
    Jae Woo Choi
    Sun Min Lim
    Jinna Kim
    Eun Joo Shin
    Min Hee Hong
    Kyoung-Ho Pyo
    Mi Ran Yun
    Dong Hwi Kim
    Hanna Lee
    Sun Och Yoon
    Da Hee Kim
    Young Min Park
    Hyung Kwon Byeon
    Inkyung Jung
    Soonmyung Paik
    Yoon Woo Koh
    Byoung Chul Cho
    Hye Ryun Kim
    BMC Cancer, 20
  • [5] Testing Personalized Medicine Using Patient-Derived Xenografts of Head and Neck Cancer
    Swick, A.
    Abel, L. J.
    Nickel, K. P.
    Hu, R.
    Yang, D. T.
    Bruce, J. Y.
    Witek, M. E.
    Hartig, G. K.
    McCulloch, T. M.
    Wieland, A.
    Harari, P. M.
    Lambert, P. F.
    Kimple, R. J.
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2018, 100 (05): : 1376 - 1377
  • [6] Differential Response to Radiation Fractionation in Head and Neck Cancer Patient-Derived Xenografts
    Musaddiq, A.
    Zenga, J.
    Frei, A.
    Shukla, M. E.
    Himburg, H. A.
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2023, 117 (02): : E253 - E253
  • [7] Generation of head and neck cancer patient-derived xenografts with in vivo acquired cetuximab resistance
    Zhou, Pei
    Li, Hua
    Wheeler, Sarah
    Grandis, Jennifer R.
    Stabile, Laura A.
    Egloff, Ann Marie
    CLINICAL CANCER RESEARCH, 2015, 21
  • [8] Patient derived xenografts as models for head and neck cancer
    Nitschinsk, Km
    Idris, A.
    McMillan, Na
    CANCER LETTERS, 2018, 434 : 114 - 119
  • [9] Patient-Derived Xenografts for Prognostication and Personalized Treatment for Head and Neck Squamous Cell Carcinoma
    Karamboulas, Christina
    Bruce, Jeffrey P.
    Hope, Andrew J.
    Meens, Jalna
    Huang, Shao Hui
    Erdmann, Natalie
    Hyatt, Elzbieta
    Pereira, Keira
    Goldstein, David P.
    Weinreb, Ilan
    Su, Jie
    O'Sullivan, Brian
    Tiedemann, Rodger
    Liu, Fei-Fei
    Pugh, Trevor J.
    Bratman, Scott V.
    Xu, Wei
    Ailles, Laurie
    CELL REPORTS, 2018, 25 (05): : 1318 - +
  • [10] Patient-derived xenografts for prognostication and personalized treatment for head and neck squamous cell carcinoma
    Karamboulas, Christina
    Bruce, Jeffrey P.
    Hope, Andrew J.
    Meens, Jalna
    Huang, Shao Hui
    Su, Jie
    Liu, Fei-Fei
    Pugh, Trevor J.
    Bratman, Scott V.
    Xu, Wei
    Ailles, Laurie E.
    CANCER RESEARCH, 2018, 78 (13)