Pan-Cancer Analyses Reveal Prognostic Value of Osteomimicry Across 20 Solid Cancer Types

Abstract

Background: Osteomimicry of cancer cells had been widely reported in prostate cancer and breast cancer. However, the prognostic value of osteomimicry in various cancer types remained unclear. We hypothesized that osteomimicry would result in remodeling of the tumor microenvironment and was eligible to predict patient prognosis. Methods: A comprehensive transcriptomic analysis of the osteomimicry, which was characterized by mRNA expression of SPARC, SPP1, and BGLAP, across 20 solid tumors (7564 patients) using RNA-seq data from The Cancer Genome Atlas (TCGA) was conducted. Samples of each cancer type were classified into subgroups (high vs. low) based on median value of osteomimetic markers, the associations of these markers with clinical outcomes, immune cell infiltration and immune checkpoints expression were explored. Results: Each osteomimetic marker harbored prognostic value in the pan-cancer analyses [SPARC: hazard ratio (HR) = 1.10, p = 0.028; SPP1: HR = 1.25, p < 0.001; BGLAP: HR = 1.13, p = 0.005]. Patients with high expression of all the three genes also had significantly unfavorable survival (HR = 1.61, p < 0.0001) compared with those of low expression. Correlation analyses demonstrated that osteomimicry was closely related to tumor purity, dendritic cells (DC) infiltration and expression of immune checkpoints. Conclusion: Osteomimicry had prognostic value in various cancer types and the underlying mechanism might correlate to the trapping and dysfunction of DCs in the tumor microenvironment, revealing the potential of osteomimicry as a target of immunotherapy.

A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer

“…ATP7B is not only involved in tumour progression, but also in the development of platinum drug resistance (14)(15)(16). A previous study reported that BGLAP was associated with advanced breast cancer staging (17). P2RX4 belongs to the P2 purinergic receptor family, which is commonly upregulated in a variety of tumours and is associated with poor prognosis (18).…”

Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients

“…Currently, data regarding the value of SPARC expression as an outcome biomarker for the various molecular subtypes of breast cancer is limited and inconsistent [22,23,51,54]. While some studies have observed that high SPARC expression was associated with poor prognosis and worse EFS and OS in several histological types [19][20][21]50,55], other studies have shown an association between low levels of SPARC and worse survival [56,57]. In their recent meta-analysis considering SPARC expression and prognosis in breast cancer, Shi et al [57] showed that low SPARC expression correlated with worse overall and distant metastasis survival rates in grade 1/2 tumors, HER2-positive tumors, and luminal A subtype tumors.…”

Mechanisms, Diagnosis and Treatment of Bone Metastases

“…This in turn promotes osteoclast-mediated bone resorption through the production of RANK-L, IL-2β, IL-6, IL-11 and tumor necrosis factor (TNF)-α, and supports evasion of an immune response [ 82 , 83 , 84 ] ( Figure 1 ). Besides breast cancer, osteomimicry has been observed across various bone metastatic cancers including prostate cancer and osteosarcoma [ 85 ].…”