STEAP3 can predict the prognosis and shape the tumor microenvironment of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by poor prognosis and difficult treatment. It has been reported that iron metabolism dysregulation is a common phenomenon in ccRCC and is closely related to the process of ccRCC. But still now, the exact function and underlying mechanisms of iron metabolism dysregulation in ccRCC have not been fully elucidated. In this study, we comprehensively investigated the prognostic value and potential role of STEAP3 (an iron metabolism-related gene) in ccRCC. STEAP3 is significantly up-regulated in ccRCC. High STEAP3 expression is associated with gender, hemoglobin level, pathological grade, tumor stage and significantly predicts an unfavorable prognosis of ccRCC patients. Functional enrichment analysis and evaluation of the tumor microenvironment indicated that STEAP3 was involved in the remodeling of tumor extracellular matrix and the shaping of an immune-suppressive tumor microenvironment to promote tumor metastasis and evade immune killing. Besides, the expression of STEAP3 is also associated with the expression of various immune checkpoint molecules and the IC50 of targeted drugs. Finally, we verified STEAP3 by RT-qPCR and IHC staining. In conclusion, we found that STEAP3 can serve as a candidate prognostic biomarker for ccRCC, and targeting STEAP3 and its biological processes may provide new references for the individualized treatment of ccRCC.

Metastatic Clear Cell Renal Cell Carcinoma to Pancreas and Distant Organs 24 Years After Radical Nephrectomy: A Case Report and Literature Review.

Background: Clear cell renal cell carcinoma (CCRCC) is a common urological neoplasm, and even though surgical resection is effective for localized CCRCC, the prognosis of metastatic CCRCC is poor. Currently, there is a paucity of recognized effective therapeutic protocols for metastatic CCRCC. Case presentation: A 76-year-old Asian man underwent radical left nephrectomy for CCRCC 26 years ago; this patient visited our hospital with abdominal pain due to multiple abdominal metastases 24 years after the nephrectomy. After metastasectomy, he underwent targeted therapy combined with a programmed death receptor-1 (PD-1) inhibitor, and the current imaging results indicate remarkable tumor remission. Conclusions: Metachronous pancreatic metastasis from CCRCC after nephrectomy is rare, but clinicians and patients should not ignore this possibility. The combination of targeted therapy and immunotherapy can result in satisfactory outcomes in cases where metastatic CCRCC continues to progress despite metastasectomy and targeted therapy. The combination of local and systemic therapy can be an effective therapeutic protocol for metastatic CCRCC, but there is no consensus on suitable therapeutics.

A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

A zinc finger protein gene signature enables bladder cancer treatment stratification.

Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.