基因SPP1,也称为骨桥蛋白(Osteopontin),是一种磷酸化的分泌蛋白,主要在骨骼和其他组织中表达。SPP1在多种生物学过程中发挥作用,包括细胞粘附、迁移、增殖和分化,以及免疫调节和炎症反应。SPP1通过与其受体整合素结合,参与细胞外基质(ECM)的相互作用,影响细胞行为和肿瘤微环境。此外,SPP1还与多种信号通路相关,如NF-κB、PI3K/Akt和Wnt/β-catenin等,调节基因表达和细胞功能。
SPP1在多种癌症中表达上调,与不良预后相关。例如,在结直肠癌中,SPP1的表达与肿瘤的侵袭和转移相关,并与免疫抑制性肿瘤微环境相关[1]。此外,SPP1的表达还与头颈部鳞状细胞癌的淋巴结转移和预后不良相关[2]。在舌鳞状细胞癌中,SPP1和FN1被确定为重要的基因生物标志物,可能用于疾病的诊断和治疗[3]。
SPP1还与肾结石疾病相关。研究发现,SPP1和UMOD基因的遗传变异与肾结石疾病的风险增加相关[4]。此外,SPP1的表达还与黑色素瘤的进展相关,并被确定为BET抑制剂治疗黑色素瘤的关键靶点[5]。
SPP1在多种癌症中的作用与其在免疫调节和炎症反应中的作用密切相关。例如,在阴茎鳞状细胞癌中,SPP1的表达与不良预后相关,并可能作为免疫治疗疗效的预测生物标志物[6]。此外,SPP1还与肺腺癌的进展相关,可能通过激活促肿瘤巨噬细胞增加肺腺癌的风险[7]。
综上所述,基因SPP1在多种生物学过程中发挥作用,包括细胞粘附、迁移、增殖和分化,以及免疫调节和炎症反应。SPP1在多种癌症中表达上调,与不良预后相关,并可能作为免疫治疗疗效的预测生物标志物。SPP1的研究有助于深入理解其在肿瘤发生发展中的作用机制,为癌症的诊断、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. Liu, Xiangxiang, Qin, Jian, Nie, Junjie, Wang, Shukui, Pan, Yuqin. 2023. ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer. In Frontiers in immunology, 14, 1185208. doi:10.3389/fimmu.2023.1185208. https://pubmed.ncbi.nlm.nih.gov/37691929/
3. 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/
4. 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/
5. 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/
6. Zou, Yuantao, Tan, Xingliang, Yuan, Gangjun, Wu, Zhiming, Yao, Kai. 2023. SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer. In Human genomics, 17, 116. doi:10.1186/s40246-023-00558-5. https://pubmed.ncbi.nlm.nih.gov/38111044/
7. Xu, Xiao-Liang, Liu, Hui, Zhang, Ying, Bao, Yang, Li, Tian-Ke. 2021. SPP1 and FN1 are significant gene biomarkers of tongue squamous cell carcinoma. In Oncology letters, 22, 713. doi:10.3892/ol.2021.12974. https://pubmed.ncbi.nlm.nih.gov/34457068/