Search

Heat shock protein family A member 5 (HSPA5) plays a pivotal role in the endoplasmic reticulum (ER) stress response and unfolded protein response (UPR), both of which are crucial for protein folding, assembly, and quality control within cells. In response to ER stress, HSPA5 becomes overexpressed to preserve cellular homeostasis. A previous study revealed a robust association between HSPA5 expression and various cancers. However, the prognostic function of HSPA5 and its involvement in tumor formation remain largely unknown. In this study, we integrated HSPA5 expression data from databases such as the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) to conduct a comprehensive pan-cancer analysis of HSPA5. Our findings revealed that HSPA5 is overexpressed in various tumor types and is significantly associated with poor prognosis. Additionally, HSPA5 expression is significantly correlated with immune checkpoints, stromal infiltration, and consequent alterations in the immune landscape. Verification was conducted on samples from patients with various tumor types, including breast and liver cancers. Additionally, we also performed verification in vitro. In conclusion, HSPA5 may offer a potential target for cancer treatment.

Additional file 1: Table S1. Clinical characteristics of patients with osteosarcoma in each dataset. Table S5. Univariate and multivariate Cox regression analysis of overall survival, relapse free survival and metastasis free survival in each data set. Figure S1. The flow diagram of this study. Figure S2. ImmuneScore and StromalScore associate with clinical features and outcomes. Figure S3. Analysis of network topology for various soft-thresholding powers. Figure S4. OS prediction value of 4 genes in the TMEindex. Figure S5. RFS prediction value of 4 genes in the TMEindex. Figure S6. Differences in survival time and TMEindex genes expression between high and low TMEindex groups. Figure S7. Stratified analysis to further determine the prognostic value of the TMEindex based on the clinical characteristics of patients. Figure S8. Progonsis prediction value of the TMEindex in osteoblastic and chondroblastic osteosarcoma in the GSE21257 cohort. Figure S9. Validation of the prognostic value of the TMEindex in GSE33382. Figure S10. GSEA enrichment plots base on KEGG gene set showing the relatively enriched pathways in TMEindex-high (A) and TMEindex-low (B) group. Figure S11. GO enrichment and KEGG pathway analysis of DEGs identified between high and low TMEindex groups. Figure S12. Pan-cancer analysis of the prognostic predictive value of TMEindex. Figure S13. Univariate Cox regression analysis reveals the association of TMEindex with the PFS of 32 tumor types.

Simple Summary Soft tissue sarcomas (STS) still lack effective clinical stratification and prognostic models. The aim of this study is to establish a reliable prognostic gene signature in STS. Using 189 STS samples from the TCGA database, a four-gene signature (including DHRS3, JRK, TARDBP and TTC3) and nomograms that can be used to predict the overall survival and relapse free survival of STS patients was developed. The predictive ability for metastasis free survival was externally verified in the GEO cohort. We demonstrated that the novel gene signature provides an attractive platform for risk stratification and prognosis prediction of STS patients, which is of great importance for individualized clinical treatment and long-term management of patients with this rare and severe disease. Abstract Soft tissue sarcomas (STS), a group of rare malignant tumours with high tissue heterogeneity, still lack effective clinical stratification and prognostic models. Therefore, we conducted this study to establish a reliable prognostic gene signature. Using 189 STS patients’ data from The Cancer Genome Atlas database, a four-gene signature including DHRS3, JRK, TARDBP and TTC3 was established. A risk score based on this gene signature was able to divide STS patients into a low-risk and a high-risk group. The latter had significantly worse overall survival (OS) and relapse free survival (RFS), and Cox regression analyses showed that the risk score is an independent prognostic factor. Nomograms containing the four-gene signature have also been established and have been verified through calibration curves. In addition, the predictive ability of this four-gene signature for STS metastasis free survival was verified in an independent cohort (309 STS patients from the Gene Expression Omnibus database). Finally, Gene Set Enrichment Analysis indicated that the four-gene signature may be related to some pathways associated with tumorigenesis, growth, and metastasis. In conclusion, our study establishes a novel four-gene signature and clinically feasible nomograms to predict the OS and RFS. This can help personalized treatment decisions, long-term patient management, and possible future development of targeted therapy.

Fragestellung: Für Weichgewebssarkome (STS), eine heterogene Gruppe seltener maligner Tumoren, fehlen effektive klinische Prognosemodelle und molekulargenetische Angriffspunkte für neue zielgerichtete Medikamente. Methodik: Von 256 STS-Patienten aus der The Cancer Genome Atlas (TCGA)-Datenbank [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

Objective: To explore the clinical features and surgical treatment experience of primary cardiac valve tumor. Methods: The present study retrospectively analyzed the clinical data of 11 patients with primary valvular tumors who underwent surgical treatment in our department from 1980 to 2016. Echocardiography of preoperative patients was indicated as a heart valve tumor. All patients underwent cardiopulmonary bypass surgery after endocardial angiography and positron emission tomography–computed tomography diagnosis, including four tumor resections–valvuloplasty and seven tumor resections–heart valve replacement. Pathological analysis was performed on all tumors. Postoperative cardiac ultrasound was followed up. Pathological analysis was performed on all tumors. All patients underwent postoperative ultrasound follow-up examination. Results: Primary valvular tumors are rare, accounting for only 0.034% (11/32.728) of extracorporeal circulation surgery in our center. It accounts for 2.8% (11/399) of primary cardiac tumors in the same period. Pathological study indicated that there were 10 cases of benign tumor and 1 case of low-grade sarcoma. After 0.6–16 years of follow-up, the operation effect was satisfactory. Conclusion: Most of these tumors are papillary fibroelastoma located on the mitral valve, and surgical operation is the best strategy for cardiac primary valve tumors.

PLOS ONE 15(5), e0233152 (2020). doi:10.1371/journal.pone.0233152, Published by PLOS, San Francisco, California, US