Key Laboratory of Zoonoses Research, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Cell Oncol (Dordr). 2023 Apr;46(2):357-373. doi: 10.1007/s13402-022-00754-w. Epub 2023 Jan 3.
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.
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.
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.
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.
癌症睾丸抗原（CTAs）是最佳的肿瘤诊断标志物，并参与肿瘤发生。然而，与结直肠癌（CRC）相关的 CTA 报道较少，其诊断能力或与肿瘤代谢重编程的相关性令人印象深刻。在此，我们证明了与 CRC 相关的 CTA，鱼精蛋白 1（PRM1），作为一种有前途的诊断标志物，并参与营养缺乏下细胞生长的调节。
使用五对 CRC 组织的转录组学筛选与 CRC 相关的 CTA。通过酶联免疫吸附测定（ELISA）检测临床样本研究 PRM1 区分 CRC 的能力。通过体内和体外实验在 CRC 细胞系中研究细胞功能。
通过 RNA-seq 和两个中心的 824 个临床样本的检测，PRM1 在 CRC 组织和患者血清中表达上调。血清 PRM1 对诊断 CRC 与健康对照和良性胃肠道疾病患者具有令人印象深刻的准确性，特别是对早期 CRC 更为敏感。此外，我们报告说，当细胞在血清减少的培养基中培养时，PRM1 的分泌上调，分泌的 PRM1 促进了培养中和小鼠中的 CRC 生长。此外，在血清缺乏的培养基中，通过激活 PI3K/AKT/mTOR 通路，PRM1 蛋白补充和过表达促进了 CRC 细胞的 G1/S 期转换。
总的来说，我们的研究将 PRM1 作为一种特异性 CRC 抗原，并说明了 PRM1 在 CRC 代谢重编程中的重要性。还为 CRC 细胞提供了新的脆弱性，未来可能成为靶向治疗的目标。PRM1 的诊断价值和生长因子样生物功能代表了受营养缺乏调节的 PRM1 的分泌过程。B 代表分泌的 PRM1 激活 PI3K/AKT/mTOR 通路。
