Clear cell renal cell carcinoma (ccRCC) frequently features a high level of tumor heterogeneity. Elucidating the chromatin landscape of ccRCC at the single-cell level could provide a deeper understanding of the functional states and regulatory dynamics underlying the disease. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on 19 ccRCC samples, and whole-exome sequencing was used to understand the heterogeneity between individuals. Single-cell transcriptome and chromatin accessibility maps of ccRCC were constructed to reveal the regulatory characteristics of different tumor cell subtypes in ccRCC. Two long noncoding RNAs (RP11-661C8.2 and CTB-164N12.1) were identified that promoted the invasion and migration of ccRCC, which was validated with in vitro experiments. Taken together, this study comprehensively characterized the gene expression and DNA regulation landscape of ccRCC, which could provide new insights into the biology and treatment of ccRCC. Significance: A comprehensive analysis of gene expression and DNA regulation in ccRCC using scATAC-seq and scRNA-seq reveals the DNA regulatory programs of ccRCC at the single-cell level.

The use of mRNAs as biomarkers serves to diagnose, treat, as well as aid the prognosis of cancer. The present study involved an analysis of mRNAs in the cell cycle at the G2 and G3 tumor grades for the prognosis of ovarian serous cystadenocarcinoma (OSC) using 364 clinical samples (G2:G3=42:322). Statistics aided the identification of NPFFR2, XPNPEP2 and CELA3B; the 3‑mRNA model that allows for classification of patients into high‑ and low‑risk groups using a median value of 0.9580745. The rates of survival varied (P=0.00149) and the independent detection of stratification of the risk of this disease was validated with success using the 3‑mRNA signature, which was demonstrated to be more successful than the weight model. This approach was revealed to provide the prognosis of grade G2 and G3 in patients with OSC compared with factors used traditionally. Compared with traditional factors, this 3‑mRNA model was demonstrated to be the only and independent prognostic factor for patients with G2 and G3 stage OSC. A literature survey was also performed in the present study in order to assess the role of the 3 genes and indirectly prove their effectiveness. The establishment of this new genetic model will enhance prospective prognosis and treatment for patients with OSC.

Nephroblastoma, also known as Wilms' tumor (WT), is the most common renal tumor that occurs in children. Although the efficacy of treatment has been significantly improved by a series of comprehensive treatments, some patients still have poor prognosis. Myelin and lymphocyte (MAL) protein, a highly hydrophobic integrated membrane‐bound protein, has been implicated in many tumors and is also closely linked to kidney development. However, the relationship between MAL and WT has not yet been elucidated. Therefore, we attempted to evaluate the feasibility of MAL as a promising prognosis factor for WT. The differential expression of MAL was investigated using TARGET database and was verified using the Gene Expression Omnibus database and real‐time quantitative PCR. The prognostic ability of MAL was determined using Kaplan–Meier and Cox regression analyses. Pearson correlation analysis was applied to explore the relationship between MAL expression and methylation sites. The ESTIMATE and CIBERSORT algorithms showed that MAL expression was associated with the WT tumor microenvironment. Gene Set Enrichment Analysis (GSEA) indicated that multiple signaling pathways closely associated with tumorigenesis were differentially enriched between the high‐ and low‐MAL groups. In conclusion, our study comprehensively explored the potential of MAL as a prognosis factor for WT. Meanwhile, we also demonstrated that MAL, as a prognostic factor for WT, may be closely related to the tumor microenvironment.

Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our study, we analyzed multiple single-cell multi-omics datasets obtained from various research teams, revealing the significant role of the activator protein 1 (AP-1) in ccRCC tumorigenesis. The motif activity analysis of transcription factors (TFs) showed a predominant activation of AP-1 in ccRCC cancer cells compared to PT cells. Furthermore, our findings at single-cell resolution revealed a notable absence of AP-1 expression in PT cells when compared to ccRCC cancer cells. In bulk-RNA of discovery cohort, no differential expression of AP-1 was detected in normal kidney and ccRCC samples, which may be attributed to confounding effects in bulk-RNA sequencing. Meanwhile, spatial transcriptomics analysis demonstrated a broader expression range of the AP-1 compared to the ccRCC marker CA9. Moreover, we observed chromatin accessibility of the AP-1 in various cell-types, including PT cells, suggesting that the transcriptional expression of AP-1 in PT cells may be influenced by subsequent transcriptional modifications, reflecting the complex regulatory mechanism of AP-1 transcription. These findings provide important insights for a deeper understanding of the function and regulatory mechanisms of AP-1 in ccRCC, thereby establishing a theoretical foundation for future clinical research and the development of treatment strategies.

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.

The genomic landscape of clear cell renal cell carcinoma (ccRCC) has a considerable intra-tumor heterogeneity, which is a significant obstacle in the field of precision oncology and plays a pivotal role in metastasis, recurrence, and therapeutic resistance of cancer. The mechanisms of intra-tumor heterogeneity in ccRCC have yet to be fully established. We integrated single-cell RNA sequencing (scRNA-seq) and transposase-accessible chromatin sequencing (scATAC-seq) data from a single-cell multi-omics perspective. Based on consensus non-negative matrix factorization (cNMF) algorithm, functionally heterogeneous cancer cells were classified into metabolism, inflammatory, and EMT meta programs, with spatial transcriptomics sequencing (stRNA-seq) providing spatial information of such disparate meta programs of cancer cells. The bulk RNA sequencing (RNA-seq) data revealed high clinical prognostic values of functionally heterogeneous cancer cells of three meta programs, with transcription factor regulatory network and motif activities revealing the key transcription factors that regulate functionally heterogeneous ccRCC cells. The interactions between varying meta programs and other cell subpopulations in the microenvironment were investigated. Finally, we assessed the sensitivity of cancer cells of disparate meta programs to different anti-cancer agents. Our findings inform on the intra-tumor heterogeneity of ccRCC and its regulatory networks and offers new perspectives to facilitate the designs of rational therapeutic strategies.