J Cancer 2021; 12(7):1978-1989. doi:10.7150/jca.50897 This issue
1. Department of Head and neck & thyroid surgery, Zhejiang Provincial People's Hospital; People's Hospital of Hangzhou Medical College, 310010, Hangzhou, Zhejiang, China.
2. Department of Pharmacy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 1# Bashan East Road, 310022, Hangzhou, China.
3. Department of Pharmacy, Zhejiang Provincial People's Hospital; People's Hospital of Hangzhou Medical College, 310010, Hangzhou, Zhejiang, China.
4. Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, 310010, Hangzhou, Zhejiang, China.
* Luo Fang and Yujia Liu contributed equally to this work.
Patient-consistent xenograft model is a challenge for all cancers but particularly for thyroid cancer, which shows some of the greatest genetic divergence between human tumors and cell lines. In this study, proteomic profiles of tumor tissues from patients, included anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma, and xenografts (8305C, 8505C, FRO, BAPAP and IHH4) were obtained using HPLC-tandem mass spectrometry and compared based on all proteins detected (3,961), cancer-related proteins and druggable proteins using pairwise Pearson's correlation analysis. The human tissue showed low proteomic similarity to the ATC cell lines (8305C, r = 0.344-0.416; 8505C, 0.47-0.579; FRO, 0.267-0.307) and to PTC cell lines (BCPAP, 0.303-0.468; IHH4, 0.262-0.509). Human tissue showed the following similarity to cell lines at the level of 135 cancer-related pathways. The ATC cell lines contained 47.4% of the cancer-related pathways (19.26%-33.33%), while the PTC cell lines contained 40% (BCPAP, 25.93%; IHH4, 28.89%). In patient tumor tissues, 44-60 of 76 and 52-53 of 93 druggable proteins were identified in ATC and PTC tumors, respectively. Ten and 29 druggable proteins were not identified in any of the ATC and PTC xenografts, respectively. We provide a reference for CDX selecting in in vivo studies of thyroid cancer.
Keywords: Proteomics, Cell-line Derived Xenografts, Primary Tumor, Thyroid Cancer.