A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center.

BACKGROUND: Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB). METHODS: Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated. RESULTS: Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients. CONCLUSION: We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.

The feasibility and safety of adopting the left lumbar vein to localize the renal artery location during left transperitoneal laparoscopic partial nephrectomy.

Background: Laparoscopic partial nephrectomy (LPN) is the standard of care for localized small renal cancer. The most critical step in this form of surgery is to localize the renal artery. In the present study, we describe a novel technique that uses the left lumbar vein (LV) to access the left renal artery during LPN. Materials and methods: This was a retrospective review of 130 cases of transperitoneal laparoscopic partial nephrectomies (TLPNs) performed on patients with renal cancer in our center between January 2018 and December 2021. Either the LV or non-lumbar vein (N-LV) technique was used to locate and manage the left renal artery. We recorded relevant clinical data from all patients, including patient characteristics, tumor data, and perioperative outcomes (artery mobilization time, operative time, estimated blood loss, and complications). Comparative analysis was then carried out between the cases using LV or N-LV vein techniques. Results: All TLPNs were successfully accomplished without conversion to open approaches. There were no complications involving the renal vessels during the entire study. The LV technique resulted in a significantly shorter time to mobilize the renal and significantly less estimated blood loss (p < 0.05). There was no significant difference between the two techniques with regard to perioperative complications. Conclusion: The left LV represents an anatomical landmark for locating the left renal artery in TLPN. This approach has numerous advantages over the transperitoneal approach including facilitating access to the left renal artery and reducing the duration of surgery.

Identification of New m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients.

N6-methyladenosine (m6A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m6A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m6A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m6A modification patterns based on 23 m6A-related genes. Next, the correlation between m6A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m6A score, was established to evaluate m6A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m6A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m6A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m6A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m6A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.

Integrative Analysis of Immune-Related Genes in the Tumor Microenvironment of Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma.

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

Comprehensive analysis of new prognostic signature based on ferroptosis-related genes in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor and the most common subtype of RCC. Ferroptosis is a novel form of regulated cell death, and ferroptosis-related genes (FRGs) have been associated with the prognosis of patients with certain cancers. However, the detailed prognostic correlation between FRGs and ccRCC has not yet been elucidated. To address this, the current study used The Cancer Genome Atlas (TCGA) dataset to explore 64 FRGs and determine their prognostic value in ccRCC. Results showed that 52 out of the 64 genes displayed significantly different expression levels in tumor tissue, and 35 out of the 52 differentially expressed genes (DEGs) were associated with overall survival. Subsequently, a four-gene prognostic signature (CD44, DPP4, NCOA4 and SLC7A11) was constructed and could successfully distinguish ccRCC patients with different prognosis in TCGA train and test sets. Furthermore, clinical ccRCC samples from our medical center were used to verify the application value of the new prognostic signature through immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Biological functional analysis implied that immune-related functions and pathways were enriched in the TCGA cohort and the immune status scores were significantly different between high- and low-risk sets. These results suggest that the four ferroptosis-related regulatory genes can act as reliable prognostic biomarkers of ccRCC, and might be exploited as potential targets of therapeutic strategies.

The Roles of CircRNAs in Bladder Cancer: Biomarkers, Tumorigenesis Drivers, and Therapeutic Targets.

Bladder cancer (BCa) is the most prevalent malignancy of the urinary system. Circular RNAs (circRNAs), a novel subtype of non-coding RNAs, play a crucial role in physiological and developmental processes. CircRNAs mainly function as regulators of splicing process and transcription, microRNA sponges, and protein brackets. Recent advances in understanding the pathogenesis of BCa have led to the identification of an abundance of dysregulated circRNAs associated with BCa. These aberrantly expressed circRNAs eventually lead to abnormalities in biological, genetic, and epigenetic information. In this review, we introduce the potential of circRNAs as biomarkers for BCa diagnosis and prognosis. Notably, diverse mechanisms have been proposed for circRNAs driving carcinogenesis, including increasing cell proliferation, promoting invasive and migratory capacity, enhancing endothelial-mesenchymal transition, sustaining stemness, and enabling resistance to chemotherapy. Importantly, a full understanding of circRNA mechanisms is needed to mine promising therapeutic approaches for targeting BCa. In this paper, we present the latest advances in circRNAs and systemically summarize the characteristics and mechanisms of circRNAs in BCa, providing potential perspectives for BCa treatment.

Comprehensive analysis of a new prognosis signature based on histone deacetylases in clear cell renal cell carcinoma.

Histone deacetylases (HDAC) family is vital for tumorigenesis and tumor progression. However, the exact role of the HDAC family in clear cell renal cell carcinoma (ccRCC) remains unclear. Based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and The Human Protein Atlas (HPA) database, we investigated and validated the expression profile, clinical significance and prognostic value of HDAC family members in ccRCC. Moreover, we further explored the correlation between HDACs and tumor microenvironment, tumor stemness, drug activity and immune subtype. The HDAC8, HDAC10, and HDAC11 manifested potential clinical value for prognosis, and the correlation analyses reveals underlying molecular mechanisms, which deserve further investigation for ccRCC. This Integrated bioinformatics analysis, based on transcriptomics and proteomics, implied that HDAC8, HDAC10, and HDAC11 may serve as potential molecular biomarkers and therapeutic targets for ccRCC, but some underlying molecular mechanisms still need to be elucidated.

NUPR1 is a novel potential biomarker and confers resistance to sorafenib in clear cell renal cell carcinoma by increasing stemness and targeting the PTEN/AKT/mTOR pathway.

BACKGROUND: Sorafenib can improve the survival of metastatic clear cell renal cell carcinoma (ccRCC) patients. However, its benefits are modest, as patients eventually become resistant, and the mechanisms remain elusive. NUPR1, a stress-induced protein, has been reported in malignancies and functions as an oncogene by modulating the stress response, facilitating survival in harsh environments and conferring drug resistance. However, its role in ccRCC has not been explored. METHODS: The expression and clinical significance of NUPR1 were analyzed in ccRCC patients in in-house patients and The Cancer Genome Atlas (TCGA) cohorts. The biological functions of NUPR1 were investigated. Xenografts were performed to confirm the effects of NUPR1 on tumorigenesis. The molecular mechanism of NUPR1 was investigated in vitro and in vivo. RESULTS: NUPR1 expression was upregulated in tumor tissue. Further analysis showed that NUPR1 overexpression was associated with an aggressive phenotype and predicted a poor prognosis. Depletion of NUPR1 suppressed tumorigenesis and sensitized cells to sorafenib treatment. Finally, mechanistic investigations indicated that NUPR1 promoted tumorigenesis in ccRCC by increasing stemness and activating the PTEN/AKT/mTOR signaling pathway. CONCLUSIONS: Collectively, our results suggest that NUPR1 may serve as a predictor of ccRCC. Notably, NUPR1 silencing reversed sorafenib resistance in ccRCC. These findings provide a novel potential therapeutic target in the clinical management of ccRCC.

Histone deacetylase 10, a potential epigenetic target for therapy.

Histone deacetylase (HDAC) 10, a class II family, has been implicated in various tumors and non-tumor diseases, which makes the discovery of biological functions and novel inhibitors a fundamental endeavor. In cancers, HDAC10 plays crucial roles in regulating various cellular processes through its epigenetic functions or targeting some decisive molecular or signaling pathways. It also has potential clinical utility for targeting tumors and non-tumor diseases, such as renal cell carcinoma, prostate cancer, immunoglobulin A nephropathy (IgAN), intracerebral hemorrhage, human immunodeficiency virus (HIV) infection and schizophrenia. To date, relatively few studies have investigated HDAC10-specific inhibitors. Therefore, it is important to study the biological functions of HDAC10 for the future development of specific HDAC10 inhibitors. In this review, we analyzed the biological functions, mechanisms and inhibitors of HDAC10, which makes HDAC10 an appealing therapeutic target.

A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder.

BACKGROUND: Bladder cancer (BC) is one of the most common malignant urological cancer in the world. Because of its characteristic of easy-recurrence and muscle-invasive, advances in our genetic understanding of bladder cancer should be translated into prognostic indicators. METHODS: We investigated 16 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) database and The Human Protein Atlas (HPA) database. The expression profile, clinical application as well as prognostic value of these genes in UC were investigated. Moreover, we further explored the correlation between RNA methylation genes and biological functions, pathways and immune status. RESULTS: Five m6A-related genes (HNRNPC, YTHDF2, YTHDF1, HNRNPA2B1, METTL3) up-regulated in UC tissues, while three regulators (ZC3H13, METTL16, FTO) down-regulated in UC. FTO and YTHDF2 show biomarker potential for the prognosis of UC patients. In addition, these identified genes may related with essential functions and core molecular pathways. CONCLUSIONS: Our research shows that two m6A RNA methylation regulators can serve as reliable prognostic biomarkers of UC, which might be exerted as potential targets of therapeutic strategies.