Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

HOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established H...

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Bibliographic Details
Published in:Scientific reports 2021-02, Vol.11 (1), p.2778-2778, Article 2778
Main Authors: Cheng, Siyuan, Yang, Shu, Shi, Yingli, Shi, Runhua, Yeh, Yunshin, Yu, Xiuping
Format: Article
Language:English
Subjects:
631/114/2164
631/208/199
631/67/589/466
Adenocarcinoma
Codes
Embryogenesis
Embryonic growth stage
Homeobox
HOX gene
Humanities and Social Sciences
multidisciplinary
Pattern formation
Prostate cancer
Retinoic acid
Science
Science (multidisciplinary)
Tissues
Transcriptomics
Tumor cell lines
Tumors
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Summary:HOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-82472-1