Cheng Siyuan, Yang Shu, Shi Yingli, Shi Runhua, Yeh Yunshin, Yu Xiuping
Department of Biochemistry and Molecular Biology, LSU Health-Shreveport, Shreveport, LA, USA.
Department of Medicine, LSU Health-Shreveport, Shreveport, LA, USA.
Sci Rep. 2021 Feb 2;11(1):2778. doi: 10.1038/s41598-021-82472-1.
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.
HOX基因编码的同源框蛋白在胚胎发育过程中控制身体模式形成；HOX基因的特定表达模式可能与组织特性相对应。在本研究中，我们利用来自24个不同解剖部位的1019个人类癌细胞系的RNAseq数据，建立了各种组织类型的HOX编码。我们将这些HOX编码应用于前列腺癌（PCa）样本的转录组图谱，发现大多数前列腺腺癌（AdPCa）样本维持前列腺特异性HOX编码，而大多数神经内分泌前列腺癌（NEPCa）样本则不然，这反映了NEPCa的间变性本质。此外，我们的分析表明，NEPCa样本与任何其他组织类型的HOX编码均无良好相关性，这表明NEPCa肿瘤失去了其前列腺特性，但并未获得新的组织特性。另外，我们通过免疫组织化学染色评估了HOXB13在前列腺中的表达，HOXB13是NEPCa中变化最显著的HOX基因。我们发现HOXB13在良性前列腺组织和AdPCa中均有表达，但在NEPCa中其表达降低或缺失。此外，我们用全反式维甲酸（ATRA）处理PCa细胞，发现降低的HOXB13表达可以恢复。这表明ATRA是一种潜在的治疗剂，可通过将NEPCa肿瘤逆转成更易治疗的AdPCa来治疗NEPCa肿瘤。
