Highlights Differential expression analysis showed a total of 304 differentially expressed genes, which were mainly related to proteoglycans in cancer, the PI3K/Akt signaling pathway, and the TGF-beta signaling pathway. The survival-related linear risk assessment model consisting of eight genes (FERMT2, ITGA5, ITGB1, MCAM, CEMIP, HGF, TGFBR1, F2RL2) was constructed. The survival rates of high-risk patients were significantly lower than that of the low-risk group, and the 3-, 5-, and 10-year AUCs were satisfactory. BMP2, BMPR2 , and GREM1 were differentially expressed in both data sets of breast cancer bone metastasis. In GSE20685 and GSE45255, significant differences in immune infiltration patterns were found between high- and low-risk groups. BMP-2 may regulate the immune infiltration process in breast cancer tissues through the PI3K/Akt signaling pathway.

Background Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities. Results From 1108 patients who underwent exome sequencing, we identified eight probands with dual molecular diagnosis and variable skeletal deformities. All eight patients had dual diagnosis consisting of two autosomal dominant diseases. A total of 16 variants in 12 genes were identified, 5 of which were of de novo origin. Patients with dual molecular diagnosis presented blended phenotypes of two genetic diseases. Mendelian disorders occurred more than once include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700). Conclusions This study demonstrated the complicated skeletal phenotypes associated with dual molecular diagnosis. Exome sequencing represents a powerful tool to detect such complex conditions.

Metastatic spinal differentiated thyroid carcinoma (MSDTC) is relatively rare in the clinic and often overlooked. The objective of the current study is to analyze the clinical characteristics and prognosis of patients with MSDTC who underwent surgical treatment to determine the prognostic factors that affect survival. Methods: This study retrospectively analyzed the clinical data and postoperative follow-up results of MSDTC patients who underwent spinal surgery at the Orthopedic Department of Peking Union Medical College Hospital from January 2010 to January 2020. Clinical data and survival time were analyzed by Kaplan-Meier analysis. Results: Eleven patients were included, and the average age was 58.3 years (range 37-74). The average time from the initial surgery to the discovery of spinal metastasis was 42.9 months (range 0-132), and the average follow-up time was 21.8 months (range 3-80). Progression was identified in seven patients, and 10 patients (90.9%) died during the followup period. Kaplan-Meier analysis showed that extraosseous visceral metastasis (p=0.012), revised Tokuhashi score (p=0.035), Tomita score (p=0.038), and surgical method (p=0.028) were associated with overall survival (OS). In addition, skeletal visceral metastasis (p=0.017), revised Tokuhashi score (p=0.028), Tomita score (p=0.038), and surgical method (p=0.049) were associated with progression-free survival (PFS). Conclusion: Surgical treatment is an effective method for treating MSDTC and leads to pain relief, restored function and increased spinal stability. Based on our single-center experience, extraosseous visceral metastasis, revised Tokuhashi score, Tomita score, and surgical methods may be potential prognostic factors for OS whilst visceral metastasis, revised Tokuhashi score, Tomita score, and surgical methods may be potential prognostic factors for PFS.