目的:肿瘤睾丸抗原(CTAs)是最佳的肿瘤诊断标记物,与肿瘤的发生有关。然而,结直肠癌(CRC)相关CTA的报道较少,具有令人印象深刻的诊断能力或与肿瘤代谢重新连接的相关性。在这里,我们展示了CRC相关的CTA,鱼精蛋白1(PRM1),作为一种有前途的诊断标记,并参与营养缺乏下细胞生长的调节。
方法:5个配对CRC组织的转录组学用于筛选CRC相关CTA。通过酶联免疫吸附测定(ELISA)检测临床样品,研究了PRM1区分CRC的能力。通过体内和体外测定在CRC细胞系中研究细胞功能。
结果:通过两个中心的824个临床样本中的RNA-seq和检测,在CRC组织和患者血清中PRM1表达上调。血清PRM1在诊断健康对照和良性胃肠道疾病患者的CRC方面显示出令人印象深刻的准确性,对早期CRC尤其敏感。此外,我们报道,当细胞在血清减少的培养基中培养时,PRM1分泌上调,分泌的PRM1促进培养物和小鼠中的CRC生长。此外,在血清缺乏的培养基中,PRM1蛋白补充和过表达通过PI3K/AKT/mTOR途径的激活促进了CRC细胞的G1/S期转变。
结论:一般来说,我们的研究将PRM1作为一种特异性CRC抗原,并说明了PRM1在CRC代谢重新连接中的重要性.CRC细胞的新脆弱性也具有将来被靶向的潜力。PRM1的诊断价值和生长因子样生物功能代表了营养缺乏调节的PRM1的分泌过程。B表示分泌的PRM1的PI3K/AKT/mTOR途径的激活。
OBJECTIVE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency.
METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays.
RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium.
CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.