Yuta Yamada

Supplementary Table 1. Data summary of patients on dialysis. Supplementary Table 2. Significantly mutated genes in tumor in patients on dialysis. Supplementary Table 3. Data summary of patients not on HD. Supplementary Table 4. Genes sepcific to ACD. Supplementary Table 5. Gene list of pure PT cells. Supplementary Table 6. Genes sepcific to the cyst cluster. Supplementary Table 7. Recurrently mutated genes detected in LMD.

Supplementary Figure 1: a, Frequencies of mutations identified in ACD-RCC (left), ESRD-ccRCC (middle), and sporadicccRCC (right). Supplementary Figure 2: a, UMAP plot of the transcriptomes of tumours from HD patients. Supplementary Figure 3: a, eGFR in the expression-defined cluster groups. The green and pink groups correspond to the groups shown in Figure 3a. Supplementary Figure 4: a, Representative images of each marker via mIHC. Supplementary Figure 5: a, Spatial expression patterns of PT genes and DT genes in the renal cortex of patients not on HD. Scale bar, 2 mm.

Patients with end-stage renal disease (ESRD) are at increased risk of acquired cystic kidney disease (ACKD) and renal tumors, but the molecular basis of such disorders remains elusive. In this study, we performed spatial immunogenomic analyses on 268 specimens from 43 patients with ACKD and associated tumors. The molecular landscape of ESRD-associated tumors is different from that of sporadic renal cell carcinoma. Single-cell and spatial analyses have shown that ACKD is under an inflammatory environment and that the renal cysts in ACKD are derived from proximal tubular cells that have survived the destructive effects of inflammation. Interestingly, we revealed that cysts are formed by clonal expansion and that paracrine activation of the MET tyrosine kinase pathway by the surrounding environment nurtures cysts. Collectively, our results identify the oncogenic mechanisms of ESRD-associated renal tumors and will pave the way for improving the prognosis of patients with ESRD.Significance:We elucidated the molecular basis of renal cancer arising in patients with ESRD and show that the inflammatory environment of ESRD gives rise to field cancerization.See related commentary by Sager et al., p. 426

Supplementary Figure 6: a, Expression patterns of PT-related gene sets in UMAP plots of the integrated scRNA-seq data of the renal cortex of 5 HD patients with ACD-RCC. Supplementary Figure 7: a, Inferred CNV profiles of cyst cells with macrophages used as references. The yellow and green clusters in each figure represent heterogeneous expression clusters of cells within the same cyst. Supplementary Figure 8: a, Expression levels of HGF (macrophage) and MET (cyst) genes in UMAP plots of the integrated scRNA-seq data.

To clarify and statistically analyze the long-term transition of urinary condition and quality of life (QOL) after robot-assisted radical prostatectomy (RARP) using some self-report questionnaires. From May 2017 to June 2021, 243 patients who underwent RARP for prostate cancer at Chiba Tokushukai Hospital were investigated retrospectively. The urinary status was observed for 5 years after surgery using the Core Lower Urinary Tract Symptom Score (CLSS), International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and International Continence Control Questionnaire-Short Form (ICIQ-SF). We used storage (IPSS-S) and voiding (IPSS-V) items separately for analysis. IPSS-S included “frequency”, “urgency”, and “nocturia”, and IPSS-V included “incomplete emptying”, “intermittency”, “weak stream”, and “straining”. The association between the results of the questionnaire and postoperative urinary continence and QOL was examined by statistical analysis. Median values of follow-up duration were 65.5 months. Items in almost all questionnaires showed the worst points 1 month after surgery and recovered thereafter. All items showed recovery to the baseline level except for “urgency incontinence” and “stress incontinence”. Preoperative IPSS-S > 7 was significantly associated with “pad-free” and “1 pad per day” status in multivariate analysis (Hazard ratio = 0.50 and 0.60, P < 0.01 and < 0.01, respectively). Urinary problems other than urinary incontinence can be restored to the baseline level after RARP. QOL differed between patients who showed a “pad-free” status and “1 pad per day” status. Additionally, preoperative IPSS-S was suggested to be a predictor of both “pad-free” status and “1 pad per day” status after surgery.

Patients with end-stage renal disease (ESRD) are at increased risk of acquired cystic kidney disease (ACKD) and renal tumors, but the molecular basis of such disorders remains elusive. In this study, we performed spatial immunogenomic analyses on 268 specimens from 43 patients with ACKD and associated tumors. The molecular landscape of ESRD-associated tumors is different from that of sporadic renal cell carcinoma. Single-cell and spatial analyses have shown that ACKD is under an inflammatory environment and that the renal cysts in ACKD are derived from proximal tubular cells that have survived the destructive effects of inflammation. Interestingly, we revealed that cysts are formed by clonal expansion and that paracrine activation of the MET tyrosine kinase pathway by the surrounding environment nurtures cysts. Collectively, our results identify the oncogenic mechanisms of ESRD-associated renal tumors and will pave the way for improving the prognosis of patients with ESRD. Significance: We elucidated the molecular basis of renal cancer arising in patients with ESRD and show that the inflammatory environment of ESRD gives rise to field cancerization. See related commentary by Sager et al., p. 426

Background: Testicular cancer progresses rapidly, and delays in diagnosis after symptom onset may lead to disease progression and increased treatment resistance. In this study, we aimed to evaluate the impact of diagnostic delay on various clinical outcomes and identify risk factors associated with delayed diagnosis in patients with testicular cancer. Methods: A retrospective observational study was conducted on 254 patients diagnosed with testicular cancer who underwent high orchiectomy at three university hospitals between March 2005 and October 2020. The clinicopathological characteristics associated with diagnostic delay and its risk factors were analyzed. Results: Among all patients, 228 (89.8%) presented with testis related symptoms, including testicular swelling or mass in 202 (79.5%), testicular pain in 34 (13.4%), and discomfort in 13 (5.1%). A delayed diagnosis, defined as an interval exceeding 53 days from symptom onset to orchiectomy, was significantly associated with a pathological tumor size ≥ 60 mm (odds ratio [OR]: 2.77, p < 0.001), elevated postoperative serum tumor markers (OR: 2.90, p < 0.001), presence of metastases (OR: 2.12, p = 0.006), clinical stage III disease (OR: 3.20, p = 0.002), and second‐line chemotherapy administration (OR: 3.36, p = 0.008). Additionally, age ≥ 36 years (OR: 1.88, p = 0.017) and absence of testicular pain (OR: 2.29, p = 0.033) were identified as independent risk factors for delayed diagnosis. Conclusion: Early medical consultation and prompt initiation of treatment following symptom onset are crucial for improving clinical outcomes in patients with testicular cancer.

We aimed to investigate the roles of tripartite motif (TRIM) proteins in urological cancers. Methods: A systematic review was conducted to investigate the oncological role of tripartite motif proteins in urological cancers. Results: A total of 84 articles were identified for the final analysis (26 articles on kidney cancers, 19 on bladder cancers, 37 on prostate cancers, and 1 on testicular cancers). In total, 27 TRIM family proteins were involved in kidney cancer, of which 9 were associated with tumor-promoting findings (TRIM24, TRIM27, TRIM37, TRIM44, TRIM46, TRIM47, TRIM59, TRIM63, and TRIM65) and of which 9 TRIM proteins were tumor-suppressive (TRIM2, TRIM7, TRIM8, TRIM13, TRIM21, TRIM26, TRIM28, TRIM33, and TRIM58). Fourteen TRIM family proteins were associated with bladder cancer (tumor-promoting: TRIM9, TRIM25, TRIM26, TRIM28, TRIM29, TRIM59, TRIM65, and TRIM66; tumor-suppressive: TRIM19 and TRIM38). Ten TRIM family proteins were associated with prostate cancer (tumor-promoting: TRIM11, TRIM24, TRIM28, TRIM33, TRIM44, TRIM59, TRIM63, TRIM66, and TRIM68; tumor-suppressive: TRIM32 and TRIM36). Twenty-eight TRIM family proteins were identified to be associated with prostate cancer (tumor-promoting: TRIM11, TRIM24, TRIM28, TRIM33, TRIM44, TRIM59, TRIM63, TRIM66, and TRIM68; tumor-suppressive: TRIM32 and TRIM36). TRIM proteins regulate urological cancers by ubiquitination or modulation of oncologic pathways. Conclusions: This review identifies TRIM proteins that are involved in urological cancers. Some of these proteins have the potential to be the therapeutic target.