基因Spp1,也称为骨桥蛋白(Osteopontin),是一种磷酸化的蛋白质,在多种生物学过程中发挥重要作用。Spp1的表达与多种疾病的发生发展密切相关,包括癌症、炎症性疾病和代谢性疾病等。
在癌症领域,Spp1的表达与不良预后和降低生存率相关。例如,在结直肠癌中,Spp1的表达与肿瘤微环境中巨噬细胞的浸润增加和免疫抑制环境相关[1]。此外,Spp1的表达还与头颈部癌的淋巴结转移相关,并可能作为头颈部癌预防和治疗的潜在靶点[2]。在黑色素瘤中,Spp1的表达与肿瘤的进展和预后相关,BET抑制剂可以通过抑制Spp1的表达来抑制黑色素瘤的进展[4]。
在炎症性疾病中,Spp1的表达与多种炎症性疾病的发生发展相关。例如,在肺纤维化患者中,Spp1的表达与肺纤维化向肺癌的进展相关,并可能作为肺纤维化治疗的潜在靶点[5]。
在代谢性疾病中,Spp1的表达与肾结石的发生发展相关。研究表明,SPP1和UMOD基因的遗传变异与肾结石的发生风险相关,且风险基因型和甲状旁腺功能亢进、高钙尿症和高草酸尿症的存在会进一步增加肾结石的发生风险[3]。
综上所述,基因Spp1在多种生物学过程中发挥重要作用,其表达与多种疾病的发生发展密切相关。Spp1可能作为潜在的治疗靶点和预后标志物,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Yu, Sifei, Chen, Mengdi, Xu, Lili, Mao, Enqiang, Sun, Silei. 2023. A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence. In Frontiers in immunology, 14, 1175490. doi:10.3389/fimmu.2023.1175490. https://pubmed.ncbi.nlm.nih.gov/37090726/
2. Feng, Shunli, Yuan, Wubin, Sun, Zhen, Zhao, Houyu, Zhuo, Xianlu. 2022. SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma. In Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 51, 620-629. doi:10.1111/jop.13333. https://pubmed.ncbi.nlm.nih.gov/35822409/
3. Patel, Yash P, Patel, Samir G, Patel, Sandip B, Ganpule, Arvind P, Desai, Mahesh R. 2023. SPP1 and UMOD gene variants are synergistically associated with risk of renal stone disease. In Gene, 863, 147264. doi:10.1016/j.gene.2023.147264. https://pubmed.ncbi.nlm.nih.gov/36804854/
4. Deng, Guangtong, Zeng, Furong, Su, Juan, Chen, Xiang, Yin, Mingzhu. 2020. BET inhibitor suppresses melanoma progression via the noncanonical NF-κB/SPP1 pathway. In Theranostics, 10, 11428-11443. doi:10.7150/thno.47432. https://pubmed.ncbi.nlm.nih.gov/33052224/
5. Chen, Tingting, Guo, Jiayu, Ai, Liqiang, Liang, Haihai, Gu, Yunyan. 2023. Up-regulated SPP1 increases the risk from IPF to lung cancer via activating the pro-tumor macrophages. In Computational and structural biotechnology journal, 21, 5751-5764. doi:10.1016/j.csbj.2023.11.018. https://pubmed.ncbi.nlm.nih.gov/38074471/