Haibing Xiao

This article presents a series of cases involving hepatic lenticular degeneration (Wilson's disease) complicated by renal tumors. It details the clinical manifestations, diagnostic procedures, treatment strategies, pathological features and outcomes of these patients. We found that this type of patient has an early‐onset disease, complex tumor pathological types, and may have a relatively poor prognosis. Through the analysis of these cases, we aim to enhance the understanding of this complex condition and provide valuable references for clinical practice.

Background: The development and implementation of telesurgery are of significant strategic importance for the future expansion and evolution of the surgical robotics industry. Telesurgery has been demonstrated to improve access to advanced medical care but also enhances the overall healthcare delivery in these underserved regions. Here, we presented a telesurgery system that optimized surgical signals via a telesurgery host using real-time signal processing and multi-source signal interaction systems. Additionally, a telesurgery network solution was developed to ensure seamless network switching. Materials and methods: We present the results of the first multi-center human study of robot-assisted laparoscopic telesurgery. Specifically, telesurgeries were performed on 18 patients across four hospitals in China utilizing EDGE MP 1000 tele-surgical systems. The distances between each pair of cities ranged from 450 km to 2200 km. Results: The telesurgery success rate was 100%. The mean real-time round-trip network latency, network jitter, video encoding/decoding latency, code rate, and video display latency were 38.38 ± 13.25 ms, 0.39 ± 0.29 ms, 20.02 ± 0.06 ms, and 12.77 ± 0.57 Mbps, 21.35 ± 3.42 ms, respectively. There was no frame loss during all telesurgeries. Conclusion: Our results indicated that telesurgery using 5G and dedicated line technology was a safe and feasible treatment option for patients with urologic oncology.

Centromere protein W (CENP-W) is essential for chromosome segregation and mitotic assembly and has been recognized as a prognostic marker in several cancers. However, its significance in clear-cell renal cell carcinoma (ccRCC) remains underexplored. To investigate this, we analyzed transcriptomic data from the National Center for Biotechnology Information (NCBI) and The Cancer Genome Atlas (TCGA) to evaluate CENP-W expression and its associations with clinical outcomes, prognosis, and immune-related markers. Kaplan–Meier survival analysis indicated that elevated CENP-W levels are significantly associated with poorer overall survival in ccRCC patients. Further meta- and multivariate analyses confirmed CENP-W as an independent negative prognostic factor. Gene Set Enrichment Analysis (GSEA) revealed the involvement of CENP-W in immune-related pathways, notably PI3K-Akt and Wnt signaling. Pearson correlation analysis revealed strong associations between CENP-W expression and immune cell infiltration, cancer-associated fibroblasts (CAFs), CTLA4, and PDCD1. qRT-PCR assays confirmed elevated CENP-W levels in ccRCC samples. Additionally, GSEA and GO enrichment highlighted a relationship between CENP-W and lipid metabolism, with reduced CENP-W expression leading to a significant decrease in lipid droplet accumulation. This study identifies CENP-W as a potential biomarker and prognostic indicator in ccRCC, offering insights into personalized therapeutic strategies integrating tumor immunity to enhance the efficacy of immunotherapy.

It has become increasingly recognised that MATN1‐AS1 is involved in multiple tumour development. The role of MATN1‐AS1 in clear cell renal cell carcinoma (ccRCC), however, is still largely unrecognised. This study investigated the molecular functions of MATN1‐AS1 in promoting ccRCC metastasis and sunitinib resistance. MATN1‐AS1 was found to be mainly located in the cytoplasm and was upregulated in ccRCC, and a positive association was seen between greater levels of MATN1‐AS1 expression and worse clinical outcomes. Downregulating MATN1‐AS1 significantly hindered cell proliferation, migration, invasion and epithelial‐mesenchymal transition (EMT). MATN1‐AS1 promoted tumour growth and metastasis in vivo. Mechanismly, MATN1‐AS1 targeted microRNA miR‐214‐5p, thereby upregulating E2F2 and promoting E2F2‐mediated EMT. We discovered that MATN1‐AS1 also promoted sunitinib resistance via E2F2 in vitro. Collectively, our research uncovered the protumor characteristics of MATN1‐AS1 and suggested it as a therapeutic target for reverse sunitinib resistance in ccRCC.

The current research revealed a strong link between lipid reprogramming and dysregulated lipid metabolism to the genesis and development of clear cell renal cell carcinoma (ccRCC). Pathologically, ccRCC exhibits a high concentration of lipid droplets within the cytoplasm. HIF-2α expression has previously been demonstrated to be elevated in ccRCC caused by mutations in the von Hippel-Lindau (VHL) gene, which plays a vital role in the development of renal cell carcinoma. Nevertheless, the mechanisms by which HIF-2α influences lipid metabolism reprogramming are unknown. Our investigation demonstrated that HIF-2α directly binds to the promoter region of LPCAT1, promoting its transcription. RNA-seq and lipidomics mass spectrometry studies showed that knocking down LPCAT1 significantly reduced triglyceride production. Research suggests that KD-LPCAT1 involves activation of the NF-κB signaling pathway, which activates F-Box/WD Repeat-Containing Protein 7 (FBXW7). FBXW7, an E3 ubiquitin ligase involved in lipid metabolism, interacts with ATP Citrate Lyase (ACLY) to promote its degradation, lowering fatty acid production and contributing to the lipid content reduction.

Emerging evidence has highlighted that dysregulation of lipid metabolism in clear cell renal cell carcinoma (ccRCC) is associated with tumor development and progression. HIF-2α plays an oncogenic role in ccRCC and is involved in abnormal lipid accumulation. However, the underlying mechanisms between these two phenomena remain unknown. Here, MED15 was demonstrated to be a dominant factor for HIF-2α-dependent lipid accumulation and tumor progression. HIF-2α promoted MED15 transcriptional activation by directly binding the MED15 promoter region, and MED15 overexpression significantly alleviated the lipid deposition inhibition and malignant tumor behavior phenotypes induced by HIF-2α knockdown. MED15 was upregulated in ccRCC and predicted poor prognosis. MED15 promoted lipid deposition and tumor progression in ccRCC. Mechanistic investigations demonstrated that MED15 acts as SREBP coactivator directly interacting with SREBPs to promote SREBP-dependent lipid biosynthesis enzyme expression, and promotes SREBP1 and SREBP2 activation through the PLK1/AKT axis. Overall, we describe a molecular regulatory network that links MED15 to lipid metabolism induced by the SREBP pathway and the classic HIF-2α pathway in ccRCC. Efforts to target MED15 or inhibit MED15 binding to SREBPs as a novel therapeutic strategy for ccRCC may be warranted.

Background: The VHL-HIF pathway and lipid droplet accumulation are the main characteristics of clear cell renal cell carcinoma (ccRCC). However, the connection between the two features is largely unknown. Methods: We used transcriptional sequencing and TCGA database analysis to identify APOL1 as a novel therapeutic target for ccRCC. The oncogenic functions of APOL1 were investigated by cell proliferation, colony formation, migration and invasion assays in ccRCC cells in vitro and xenografts derived from ccRCC cells in vivo. Oil red O staining and quantification were used to detect lipid droplets. Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assays were carried out to identify HIF-2α bound to the promoter of APOL1 and lncRNA LINC02609. RNA-FISH and luciferase reporter assays were performed to determine that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p. Findings: RNA-seq data revealed that HIF2α can regulate APOL1 and lncRNA LINC02609 expression. We also found that HIF-2α can bind to the promoter of APOL1 and lncRNA LINC02609 and transcriptionally regulate their expression directly. We further demonstrated that LncRNA LINC02609 functions as a competing endogenous RNA to regulate APOL1 expression by sponging miR-149-5p in ccRCC. Mechanistically, APOL1-dependent lipid storage is required for endoplasmic reticulum (ER) homeostasis and cell viability and metastasis in ccRCC. We also showed that high APOL1 expression correlated with worse clinical outcomes, and knockdown of APOL1 inhibited tumor cell lipid droplet formation, proliferation, metastasis and xenograft tumor formation abilities. Together, our studies identify that HIF2α can regulate the expression of the lipid metabolism related gene APOL1 by direct and indirect means, which are essential for ccRCC tumorigenesis. Interpretation: Based on the experimental data, in ccRCC, the HIF-2α/LINC02609/APOL1 axis can regulate the expression of APOL1, thus interfering with lipid storage, promoting endoplasmic reticulum homeostasis and regulating tumor progression in ccRCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future studies in ccRCC.

Background: Eukaryotic initiation factor 3a (EIF3A), a “reader” protein for RNA methylation, has been found to be involved in promoting tumorigenesis in a variety of cancers. The impact of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be reported. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between EIF3A expression and immune infiltration. Methods: We collected 29 m6A-related mRNA data and clinicopathological parameters from The Cancer Genome Atlas (TCGA) database. Logistic regression analyses were used to analyse the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) was applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize independent factors associated with overall survival (OS) and disease-free survival (DFS). The nomogram aimed to predict the 1-, 3- and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to determine the potential functions and related signalling pathways of EIF3A expression. To investigate EIF3A of coexpressed genes, we used LinkedOmics, and the results were subjected to enrichment analysis. Simultaneously, LinkedOmics and STRING datasets were used to identify EIF3A coexpressed genes that were visualized via Cytoscape. Finally, we evaluated whether EIF3A expression correlated with the infiltration of immune cells and the expression of marker genes in ccRCC by Tumour Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was correlated with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with a poor prognosis. The results of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that EIF3A high expression was enriched in the renal cell carcinoma pathway. EIF3A expression was significantly positively correlated with B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most marker genes of immune cells. Conclusions: EIF3A could serve as a potential biomarker for prognostic and diagnostic stratification of ccRCC and is related to immune cell infiltrates.