Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans ; Carcinoma, Renal Cell/therapy* ; Immunotherapy ; Glycolysis ; Metabolic Reprogramming ; Kidney Neoplasms/therapy* ; Tumor Microenvironment

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare neoplasm of the kidney. Recognition of this rare entity is important with regards to a patient’s prognosis and therapeutic management.
Kidney Neoplasms ; Immunohistochemistry ; Pathology, Surgical

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.
Humans ; Carcinoma, Renal Cell/genetics* ; Immunotherapy ; Kidney ; Kidney Neoplasms/genetics* ; Prognosis ; Copper ; Apoptosis

OBJECTIVE: To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism. METHODS: In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment. RESULTS: Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate. CONCLUSION Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.
Animals ; Mice ; Carcinoma, Renal Cell/metabolism* ; Curcumin/therapeutic use* ; MicroRNAs/metabolism* ; Mice, Nude ; Cell Line, Tumor ; Kidney Neoplasms/metabolism* ; Autophagy ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; ADAMTS Proteins/metabolism*

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
Humans ; Carcinoma, Renal Cell/pathology* ; Cell Proliferation ; Hypoxia ; Kidney Neoplasms ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; RNA, Circular/metabolism* ; RNA, Small Interfering ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*

OBJECTIVE: To investigate and summarize the clinicopathological features, immunophenotype, differential diagnosis and prognosis analysis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: The data of thirteen cases of MTSCC were retrospectively analyzed, the clinical and pathological characteristics and immunohistochemical expression were summarized, and fluorescence in situ hybridization was detected. RESULTS: Among the thirteen patients, four were males and nine females, with a male-to-female ratio of 1 ∶2.25. The average age was 57.1 years, ranging from 39 to 78 years. The maximum diameter of the tumor was 2-12 cm. All cases had no symptoms, and were accidentally discovered, 3 cases underwent partial renal resection, 10 cases underwent radical renal resection, 9 cases were located in the left kidney, and 4 cases were located in the right kidney. Most of the cases showed the classical morphological changes, with 11 cases of nuclear grading [World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system] being G2 and 2 cases being G3. There were 6 cases of stage PT1a, 3 cases of PT1b, 2 cases of PT2a, and 1 case of PT2b and 1 case of PT3a. The positive rates of immunohistochemical staining were: vimentin, AE1/AE3, α-methylacyl-CoA racemase (αMACR) and cytokeratin (CK) 8/18, 100% (13/13); CK7, 92.3% (12/13); epithelial membrane antigen (EMA), 92.3% (12/13); CK20, 46.2% (6/13); CD10, 30.8% (4/13); synaptophysin (Syn), 7.7% (1/13); chromogranin A (CgA), CD57, WT1 and Ki-67, 0 (0/13), and fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and 17 were observed in any of the cases. The follow-up period was 6 months to 7 years and 6 months, 2 cases died after lung metastasis (one with ISUP/WHO grade G3, one with necrosis), and the remaining 11 cases had no recurrence and metastasis. CONCLUSION MTSCC is a unique type of low-grade malignancy kidney tumor, occurs predominantly in females, widely distributed in age, the current treatment method is surgical resection, and cases with necrosis and high-grade morphology are prone to recurrence and metastasis, although most cases have a good prognosis, but they still need close follow-up after surgery.
Humans ; Male ; Female ; Middle Aged ; Kidney Neoplasms/surgery* ; Carcinoma, Renal Cell/diagnosis* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Adenocarcinoma, Mucinous/pathology* ; Kidney/pathology* ; Prognosis ; Necrosis

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Carcinoma, Renal Cell/diagnosis* ; Retrospective Studies ; Kidney ; Carcinoma ; Kidney Neoplasms/diagnosis*

OBJECTIVE: To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process. METHODS: We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQ^TM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed. RESULTS: We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores < 60) in terms of GTV, PGTV (CI) and PGTV (V_{66 Gy}) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D_98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V_{60 Gy}, D_98%), PCTV (CI), and CTV (D_98%) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P < 0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (D_min) and PTV (V_{45 Gy}, D_98%) (P < 0.05) with significantly reduced doses of the small intestines (V_{40 Gy} vs V_{30 Gy}), the colon (V_{40 Gy} vs V_{30 Gy}), and the bladder (D_35%) (P < 0.05). CONCLUSION Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process.
Humans ; Female ; Uterine Cervical Neoplasms/radiotherapy* ; Rectum ; Colon ; Kidney ; Organs at Risk