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Purpose: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68 Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC., Methods: The in vivo and ex vivo biodistribution of 68 Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied., Results: NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68 Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68 Ga-NY104 uptake., Conclusion: 68 Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68 Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC., Trial Registration: The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Liquid biopsy is a noninvasive technique that can provide valuable information for disease characterization by using biofluids as a source of biomarkers. Proteins found in biofluids can offer a wealth of information for understanding pathological processes. In this study, we used early-stage clear cell renal cell carcinoma (ccRCC) as a model to explore the proteomic relationships among tissue, plasma, and urine. We analyzed samples of tumor tissue, plasma, and urine from a cohort of 27 ccRCC patients with T1-2 stage and 27 matched healthy controls, using liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis. We integrated the differential proteins found in the three types of samples to explore ccRCC-associated molecular changes. Our results showed that both plasma and urine proteomes could reflect functional changes in tumor tissue. In plasma, cytoskeletal proteins and metabolic enzymes were differentially expressed, while in urine, adhesion molecules and defense proteins showed differential levels. The differential proteins found in plasma and urine both reflect the binding and catalytic activity of tumor tissue. Additionally, proteins only changed in biofluids could reflect body immune response changes, with plasma proteins involved in actin cytoskeleton and oxidative stress, and urine proteins involved in granulocyte adhesion and leukocyte extravasation signaling. Plasma and urine proteins could effectively distinguish RCC from control, with good performances (plasma/urine: 92.6%/92.6% specificity, 96.3%/92.6% sensitivity, and an area under the curve of 0.981/0.97). In conclusion, biofluids could not only reflect functional changes in tumor tissue but also reflect changes in the body's immune response. These findings will benefit the understanding of body biomarkers in tumors and the discovery of potential disease biomarkers., Competing Interests: Conflicts of interest All authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Juxtaglomerular cell tumor (JGCT) is a very rare disease, and surgical resection is the only possible way to cure this tumor. Open nephrectomy and partial nephrectomy have been reported to manage JGCTs with excellent results in the previous reviews. Laparoscopic surgery has been popularized in recent years, while critical issues associated with laparoscopic surgical management have been seldom reported. We summarized the JGCTs in our center to discover the optimal surgical management and its anatomic foundation., Methods: In this retrospective study, we enrolled a total of 14 JGCT patients. All patients received surgeries and were followed up for up to 11 years. We mainly summarized the size and location of tumors, imaging features, and surgical strategies. A descriptive statistical analysis was performed., Results: The JGCTs in this study had a median size of 1.35 cm and all located superficially, mainly in the cortical or subcortical area of the kidney. All 14 patients had hypertension, ten had hypokalemia, and seven had elevated plasma renin activity. Pathologically, JGCT cells were polygonal or spindle shape, with positive CD34 and vimentin immunostaining. All patients received partial nephrectomy; nine were laparoscopic, and five were open. Laparoscopic partial nephrectomy (LPN) was performed in seven out of eight patients over the last nine years. Postoperative blood pressure, serum potassium, and plasma renin activity were normal in all patients. No recurrence occurred within a median follow-up of 60 months., Conclusion: The small size and superficial location are the characteristic anatomic features of JGCT; they suggest that LPN is the preferred surgical strategy. Laparoscopic ultrasound is helpful for the intraoperative detection of small JGCTs. Longer follow-up is required to examine the biological behavior of JGCTs and the effect of LPN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Fan, Tong, Xiao and Zhang.)

Background and Objectives: Circulating tumor cells (CTCs) as a noninvasive detection technology have become a research hotspot in the field of precision medicine. However, CTC detection faces great challenges with respect to specificity and sensitivity., Methods: We divided 39 subjects into three groups: renal carcinoma, renal stones and healthy persons. Using subtraction enrichment (SE) combined with immunostaining-fluorescence in situ hybridization technology, we identified and characterized CTCs. CTCs were identified as DAPI +/CD45-/PanCK + (-). We explored whether the number of CTCs was related to clinicopathological factors and their clinical application., Results: The CTC count in the renal carcinoma group (29/39) was 86.20% using a cut-off value of 1 CTC, which was significantly higher than that of other technologies in detecting CTCs, demonstrating that SE-iFISH technology can be used for CTC detection. The CTC count was much higher in the renal carcinoma group than that in the other control groups, with an area under the ROC curve of 0.931 (95% confidence interval 0.851 to 1.000, P < 0.01). In addition, the tetraploid count on chromosome 8 of T4 stage renal carcinoma was much higher than that of other stages (T1-T3), which may suggest that tetraploid count could be a marker of renal carcinoma prognosis and influence treatment decisions for better clinical management., Conclusions: Our study showed that SE-iFISH technology can be used to detect CTCs in renal carcinoma with high sensitivity and specificity. Therefore, the analysis of CTCs with SE-iFISH has clear potential to improve the management of patients with renal carcinoma.

Background: Renal cell carcinoma (RCC) is the most common and lethal malignancy of the kidney. Distinguishing RCC from benign renal tumors and healthy controls is still a clinical challenge. Urine metabolomics has been used to identify biomarkers of clinical diseases., Methods: In the present study, we explored the urine metabolomes of a cohort of 61 patients with renal tumors (39 RCC and 22 benign renal tumors) and 68 healthy controls using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS)., Results: Metabolic profiling of urine could significantly differentiate RCC from healthy controls and benign renal tumors. Metabolic pathways, including lysine metabolism and phenylalanine metabolism, were found to be disturbed in the RCC group. Steroid hormone biosynthesis was significantly different between the benign tumor group and the RCC group. RCC biomarkers were further explored. A metabolite panel consisting of cortolone, testosterone and L-2-aminoadipate adenylate was discovered to have good ability of distinguishing RCC from benign tumors, with an AUC of 0.868 for tenfold cross-validation and 0.873 for the validation group. In addition, the panel of aminoadipic acid, 2-(formamido)-N1-(5-phospho-D-ribosyl) acetamidine and alpha-N-phenylacetyl-L-glutamine could distinguish the RCC group from the healthy control group, with an AUC of 0.841 for tenfold cross-validation and 0.894 for the validation group., Conclusions: This pilot study suggests that urine metabolomics may be useful in differentiating RCC from healthy controls and benign renal tumors.

Background: To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC., Methods: In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways., Results: The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria., Conclusions: UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC.

Background: Renal cell carcinoma metastasizing to rectum is very rare, and the unusual metastatic sites should be paid attention to during the follow-up of renal cell carcinoma., Case Summary: We describe a case of a 65-year-old male who was diagnosed with metastatic renal cell carcinoma to rectum 10 years after the right radical nephrectomy. Histopathology and immunohistochemical examinations contribute to making differential diagnosis between rectal metastasis of renal cell carcinoma and primary rectal clear cell carcinoma. Positron emission tomography-computed tomography with fluorodeoxyglucose shows hypermetabolic activity in upper rectum and other sites of metastasis at the same time., Conclusion: Possibility of unusual metastatic sites of renal cell carcinoma such as rectum indeed exists, which should not be ignored in the surveillance after resection of the primary tumor., Competing Interests: The authors report no conflicts of interest.

MicroRNA-206 (miR-206) has been discovered to have anticancer properties in different tissues. However, the role of miR-206 on renal carcinoma is still ambiguous. In the present study, we investigated the role of miR-206 on the development of renal carcinoma. The results indicated that miR-206 was significantly downregulated in 69 clear cell renal carcinoma (ccRCC) tissues and low-level of miR-206 related to shorter metastasis-free survival time for patients with ccRCC. The results indicated that vascular endothelial growth factor A (VEGFA) was a direct target of miR-206 in renal cancer cells. Further studies revealed that upregulation of miR-206 inhibited renal cancer cell proliferation, invasion and migration, suggesting that miR-206 functioned as a tumor suppressor. RNA interference targeting VEGFA mRNA could mimic the upregulation of miR-206 functions, and also suppressed tumor formation in vivo in nude mice. These results suggest that miR-206 plays an important role in ccRCC tumorigenesis by targeting VEGFA.

Purpose: Several prognostic models have been developed to assess the efficacy and safety of sorafenib for metastatic renal cell carcinoma (mRCC), but few studies have validated its use in Chinese patients. The objective of this single center, single arm retrospective study was to examine the efficacy and safety of sorafenib and its related prognostic clinico-pathologic factors in Chinese mRCC patients., Methods: One hundred thirty four mRCC patients were enrolled. All patients received 400 mg of sorafenib orally twice daily. The dose was subsequently adjusted in the event of treatment-induced toxicity. Tumor response, progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were determined., Results: The median PFS and OS were 10 months (1-36 months) and 22 months (2-37 months), respectively. Complete, partial, and stable disease were observed in two (1.49%), 24 (17.91%), and 99 (73.88%) patients, respectively. Hand/foot skin reactions, diarrhea and fatigue were the most commonly observed AEs following sorafenib treatment. Among the AEs, only 13 grades 3 and 4 were observed. Multivariate analysis revealed that independent predictive factors for PFS included Eastern Cooperative Oncology Group (ECOG) status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk status, and bone metastasis (all p < 0.05). Factors associated with OS included MSKCC risk values, bone metastasis and sorafenib-induced hypertension (all p < 0.05)., Conclusion: The introduction of sorafenib therapy for mRCC in Chinese patients may lead to a favorable disease control with acceptable tolerability. In addition, the parameters predicting favorable outcomes, including ECOG status, MSKCC risk status and bone metastasis, may have prognostic value in clinical practice.

Objectives: To analyze the survival and the associated factors affecting the prognosis of renal cell carcinoma (RCC) in China with a sufficiently large sample size., Methods: Clinical data with complete follow-up of 1326 RCC patients were successfully obtained. Progression-free survival (PFS) and cancer-specific survival (CSS) were calculated, survival analysis was performed by Kaplan-Meier analysis, and Cox proportional hazards regression models were served to estimate the prognostic significance of each variables., Results: The median length of follow-up was 43.55 months (25-75 %, 25.47-68.75 months). During follow-up, 147 patients developed RCC-related progression, with a median PFS of 18.2 months (25-75 %, 7.50-47.27); 64 patients died from RCC-related progression, with a median CSS of 27.67 months (25-75 %, 14.10-58.53). For RCC patients in T1 stage, 3-, 5-, 8-, and 10-year CSS rates of patients receiving nephron-sparing nephrectomy were 99.33, 98.21, 97.40, and 97.40 %, respectively, which were significantly higher than radical nephrectomy patients (97.88, 96.28, 95.09, and 88.58 %, respectively). Cox proportional hazards regression model showed that tumor N stage, signs of lung metastasis (such as cough and hemoptysis), signs of bone metastasis (such as bone pain and fracture), pathological subtype of RCC, microscopic sarcomatoid change, and progression were prognosis factors for Chinese RCC patients., Conclusions: Tumor stage, nephrectomy type, lung metastasis, bone metastasis, pathological subtype, sarcomatoid change, and type of progression were important risk factors for RCC. For T1 stage RCC patients, nephron-sparing nephrectomy showed better CSS than radical nephrectomy, which may guide the doctors and patients in their choices of surgical procedures.

Objective: To evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC)., Materials and Methods: Clinical data of 18 patients with high risk RCC who received surgery done successfully after preoperative neoadjuvant therapy with sorafenib in Peking Union Medical College Hospital (PUMCH) from April 2007 to October 2013 have been reviewed and analyzed in this study., Results: Among the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR) of the operation on the selected patients is very high (94.4%), including 4 cases (22.2%) of partial response (PR) and 13 cases (72.2%) of stable disease (SD). After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm) to 6.2 cm (ranging from 2.4 to 16.8 cm), and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II., Conclusion: Preoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS) or radical nephrectomy to be done successfully.

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC.