The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and antiandrogen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. Secreted phosphoprotein 1 (SPP1) is a cardinal mediator of tumor-associated inflammation and facilitates metastasis. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, and metastatic levels in CRPC progression and investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, polymerase chain reaction (PCR), immunohistochemical staining, and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC and enzalutamide resistance. SPP1 knockdown enhanced enzalutamide sensitivity and repressed invasion and migration of prostate cancer cells. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrated that SPP1 overexpression maintains the activation of PI3K/AKT and ERK1/2 signaling pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression and help to discover new potential targets against mCRPC.

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Various survival scoring systems have been developed to help surgeons select the best candidates for appropriate therapies in patients with metastatic spinal disease. This study aims to discuss the current status and future directions of scoring systems for the prediction of survival prognosis in these patients. The search terms “spine metastases,” “metastatic spinal disease,” and “metastatic spinal cord compression” were combined with “survival prognosis,” “scoring system,” and “score” to elicit relevant literatures in PubMed and Embase databases. As a result, 159 articles were selected from PubMed, and 246 articles were extracted from Embase. After reviewing each article, we carefully included and analyzed 74 articles about the development and evaluation of scoring systems for predicting survival prognosis in spine metastases. In this review, those scoring systems were stratified into the historic scoring systems and the modern scoring systems on the basis of the proposed time. The historic scoring systems, including the original/revised Tokuhashi scoring system, the Bauer scoring system, the Tomita scoring system, and the Linden scoring system, and the modern scoring systems, such as the Lei scoring system, the Bartels scoring system, the Mizumoto scoring system, the Bollen scoring system, the Rades scoring system, Oswestry Spinal Risk Index, and the Choi risk calculator, were introduced and discussed in this review. Besides, the clinical effectiveness and pitfalls of the existing systems and the future directions of the next generation of scoring systems were also addressed and discussed. We recommended these scoring systems as preferable reference tools to help doctors to select surgical candidates. In patients with long-term life expectancy, radical surgery, such as wide or marginal excision, can be considered in patients with neurological deficits, spine instability, or severe back pain. Besides, with the advancement and improvement of medical technologies, surgical procedures are changing, which can affect surgical indications such as vertebroplasty, minimal invasive surgery, and percutaneous stabilization, which can also be used in patients with spine instability or severe back pain, and do not require much recovery; hence, they can even be used in patients with relative short-term life expectancy. However, the decision about the treatment of patients with metastatic spinal disease is so complicated and should never rely on prognostic scores alone. The final therapeutic decision should be made by interdisciplinary corporations of oncologists, radiologists, and spinal surgeons. Besides, individual intentions should be respected.

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