MiR-15b-5p Promotes Growth and Metastasis of Renal Clear Cell Carcinoma / MiR-15b-5p Promueve el Crecimiento y la Metástasis del Carcinoma Renal de Células Claras

SUMMARY: We investigated the expression and clinical significance of miR-15b-5p in clear cell renal cell carcinoma (RCC) through bioinformatics analysis and experimental verification. The differentially expressed miRNAs were screened in the GEO database. Venn diagram showed that there were 5 up-regulated miRNAs (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p, and has-miR-193a-3p) and only 1 down-regulated miRNA (has-miR-532-3p) that were commonly expressed between GSE189331 and GSE16441 datasets. This was further confirmed in TCGA. Further analysis showed that the has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p, and has-miR-15b-5p were closely related to tumor invasion, distant metastasis and survival probability. The expression of miR-15b-5p in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues (P0.05). Following inhibition of miR-15b-5p expression, RCC cells had attenuated proliferation, increased apoptosis, and attenuated migration and invasion. has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC. miR-15b-5p is highly expressed in cancer tissues of ccRCC patients. It may promote proliferation, inhibit apoptosis and enhance cell migration and invasion of RCC cells. The has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, and has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC.

Investigamos la expresión y la importancia clínica de miR-15b-5p en el carcinoma de células renales (CCR) de células claras mediante análisis bioinformático y verificación experimental. Los miARN expresados diferencialmente se examinaron en la base de datos GEO. El diagrama de Venn mostró que había 5 miARN regulados positivamente (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p y has-miR-193a-3p). ) y solo 1 miARN regulado negativamente (has-miR-532-3p) que se expresaron comúnmente entre los conjuntos de datos GSE189331 y GSE16441. Esto fue confirmado aún más en TCGA. Un análisis más detallado mostró que has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p y has-miR-15b-5p estaban estrechamente relacionados con la invasión tumoral, la metástasis a distancia y la probabilidad de supervivencia. La expresión de miR-15b-5p en tejidos ccRCC fue significativamente mayor que la de los tejidos renales normales adyacentes (P 0,05). Tras la inhibición de la expresión de miR-15b-5p, las células RCC tuvieron una proliferación atenuada, un aumento de la apoptosis y una migración e invasión atenuadas. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC. miR-15b-5p se expresa altamente en tejidos cancerosos de pacientes con ccRCC. Puede promover la proliferación, inhibir la apoptosis y mejorar la migración celular y la invasión de células RCC. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E y has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC.

Can CXCL13 be a prognostic marker in clear cell renal cell carcinoma?

Background: CXCL13, B-lymphocyte chemoattractant, has been associated with many diseases and cancers. One of the malignancies that CXCL13 has been investigated is clear cell renal cell carcinomas which are the most common subtype of renal cancers. Aims and Objectives: The aim of this study is to evaluate the immunohistochemical staining patterns of CXCL13 in clear cell renal cell carcinomas and to determine its relationship with pathological tumor stage, risk factors, and prognostic parameters. Materials and Methods: In this study, 99 patients who underwent partial/radical nephrectomy diagnosed with clear cell renal cell carcinoma were included. Four micron sections were taken from paraffin embedded blocks containing sufficient tumor and kidney tissue. Samples were immunohistochemically stained with CXCL13 antibody. During microscopic examination, CXCL13 positive stained cells in ten high magnification fields were counted and evaluated using a semiquantitative H score: 3 × strongly stained + 2 × moderately stained + 1 × weakly stained. The cut-off value was set as 40 for values between 0 and 300. The low and high stained groups were compared with prognostic parameters and risk factors. Statistics: The difference of continuous variables between the two groups was examined with the t test and the distribution of categorical variables with the Chi-square test. A value of P < 0.05 was considered to be statistically significant. Results: The number of lymphocytes stained with CXCL13 in the tumor was higher than in the normal kidney parenchyma (p = 0.07). Intratumoral lymphocytes were highly stained with CXCL13 in 57.5% of pT3 cases and 31.7% of pT1 cases. The amount of intratumoral lymphocytes stained with CXCL13 increased in advanced pathological stages (p = 0.05). Nonsmoking cases were mostly in the low staining group (p = 0.06). Conclusion: The relationship we found between advanced pathological stage and intratumoral CXCL13 staining in our study suggests that CXCL13 has a prognostic value in this cancer.

Comparison of diagnostic performance of Clear Cell Likelihood Score v1.0 and v2.0 for clear renal cell carcinoma / 南方医科大学学报

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.

Clinicopathological features and prognosis of clear cell papillary renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the clinicopathological features and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). 【Methods】 The clinicopathological and follow-up data of 40 CCPRCC patients treated during Jun. 2011 and Oct.2021 were retrospectively analyzed. The prognosis was compared with that of 40 cases of clear cell renal cell carcinoma (ccRCC) and 19 cases of papillary renal cell carcinoma (PRCC) treated in the same period. Survival analysis was performed by Log-rank test and Kaplan-Meier survival curves were plotted. 【Results】 Among the 40 patients, 28 were male and 12 were female, aged 31-84 years; 38 cases had unilateral and 2 cases had bilateral tumors; 3 cases had multifocal lesions. All patients received surgery. The maximum diameter of the masses ranged from 3.0 to 95.0 mm, with an average of (27.6±18.1) mm. Pathological grade was Fuhrman 1-2 in all cases. Immunohistochemical tests were positive for CK7 and CA-IX. During the follow-up of 5-129 (average 56) months, 1 case died after bone metastasis, 2 had ipsilateral recurrence, and 1 developed primary esophageal cancer. CCPRCC patients had a significantly better prognosis than CCRCC (P<0.001) and PRCC (P=0.005) patients, while there was no significant difference in the prognosis between CCRCC and PRCC patients (P=0.93). 【Conclusions】 CCPRCC has low malignancy. The diagnosis relies on characteristic pathological and immunohistochemical features. Surgery is an effective treatment. CCPRCC has a better overall prognosis than CCRCC and PRCC.

Efficacy of targeted drugs for metastatic non-clear cell renal cell carcinoma:a Meta-analysis / 现代泌尿外科杂志

【Objective】 To systematically evaluate the efficacy and safety of targeted drugs in the treatment of metastatic non-clear cell renal cell carcinoma (nccRCC) and to provide guidance for clinical treatment. 【Methods】 All observational studies and randomized controlled trials (RCTs) of nccRCC treated with targeted drugs were retrieved from the PubMed, Embase, the Cochrane Library and Web of Science. Three independent investigators screened the literature, extracted data and evaluated the quality of literature. The RCTs were evaluated using the Cochrane Handbook. One research with insufficient outcome data (follow-up bias) was assessed as high risk, and the other studies showed low or uncertain risk. The non-RCTs were evaluated with the JBI Quality Assessment Tool, and all studies displayed a low risk of bias. The data were analyzed with Stata 17.0 software. 【Results】 A total of 16 studies involving 989 patients were included. Meta-analysis showed that the objective response rate (ORR) was 12.6% (95%CI:8.1%-17.9%), the total disease control rate (DCR) was 65.3% (95%CI:58.3%-72.1%), the total median progression-free survival (PFS) was 5.80 (95%CI:4.69-6.91) months, and the median overall survival (OS) was 15.93 (95%CI:12.17-19.68) months. In subgroup analysis, the total ORR of patients with metastatic nccRCC treated with sunitinib and cabozantinib were 11.7% (95%CI:6.5%-18.0%) and 17.2% (95%CI:8.4%-28.2%), respectively. The total ORR of patients with papillary renal cell carcinoma was 9.1% (95%CI:2.4%-18.9%). 【Conclusion】 Targeted drugs have a significant effect on patients with metastatic nccRCC, but adverse reactions may occur. Targeted drugs have poor effects on metastatic papillary renal cell carcinoma, and cabozantinib may have greater survival benefits.

Expression of POU2F2 in clear cell renal cell carcinoma and its effects on the biological behavior of the cancer cells / 现代泌尿外科杂志

【Objective】 To investigate the expression of transcription factor POU domain class 2 transcription factor 2 (POU2F2) in clear cell renal cell carcinoma (ccRCC) and human renal cancer cell lines (786-O and ACHN) and its effects on the cells’ biological behaviors such as proliferation, migration and invasion in vitro. 【Methods】 The mRNA expressions of POU2F2 in ccRCC tissues, adjacent normal tissues, cell lines 786-O and ACHN were detected with real-time polymerase chain reaction (qRT-PCR). The protein expression of POU2F2 in ccRCC tissues and adjacent normal tissues were detected with immunohistochemistry. The effects of knockdown of POU2F2 on the mRNA and protein expressions of epithelial mesenchymal transformation (EMT)-related tumor markers were detected with qRT-PCR and Western blot. 【Results】 The mRNA expression of POU2F2 in ccRCC tissues was significantly higher than that in adjacent normal tissues, and was correlated with patients’ gender, WHO/ISUP nuclear grade and TNM stage. The protein expression of POU2F2 was significantly higher in ccRCC tissues than in adjacent normal tissues, and was correlated with tumor pathological grade and TNM stage. The mRNA expression of POU2F2 was significantly decreased in 786-O cells after sh-POU2F2-1013 plasmid transfection (P<0.05); the proliferation ability, clonal formation rate, migration ability and invasion ability were significantly reduced (P<0.05). Knockdown of POU2F2 down-regulated the mRNA and protein expressions of MMP2, MMP9 and Twist in 786-O cells, while up-regulated E-ca expression. 【Conclusion】 The mRNA expression of POU2F2 was significantly up-regulated in ccRCC tissues and renal cancer cells. Knockdown of POU2F2 inhibited the proliferation, migration and invasion of cells in vitro, and slowed or inhibited the occurrence and development of renal cancer.

Bioinformatic analysis of the expression of KIF14 and its clinical significance and biological functions in clear cell renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the expression of Kinesin family member 14 (KIF14), and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma (ccRCC). 【Methods】 The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA, GEO and Ualcan databases. The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method. The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER. The protein-protein interaction network of KIF14 was conducted with Genemania. The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software. The biological functions of KIF14 were verified with in vitro functional assay. 【Results】 KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage, pathological grade, and lymphatic metastasis, but negatively correlated with clinical prognosis. KIF14 expression was an independent risk factor for overall survival of ccRCC patients. GO annotations showed that KIF14 was involved in DNA replication, nuclear division, organelle fission, and cell adhesion. KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway. Genemania analysis indicated KIF14 interacted with CENPE, CIT, KIF23, and other proteins. Timer showed that KIF14 was positively correlated with immune cell infiltration. Knockdown of KIF14 expression suppressed cell proliferation, migration, and invasion of ccRCC. 【Conclusions】 KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.

Transcriptome analysis of checkpoint kinase 2 in clear cell renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To explore the expression of checkpoint kinase 2 (CHEK2) in clear cell renal cell carcinoma (ccRCC), its association with the clinicopathological features and prognosis, and to predict its relevant molecular signaling pathways and biological functions. 【Methods】 The gene expression data, phenotype data, and corresponding survival information of ccRCC patients were downloaded from TCGA database. The optimal cutoff value of CHEK2 was determined with the "survminer" package. The patients were divided into low and high expression groups, and the association between CHEK2 expression and clinicopathological features was analyzed. The correlation between CHEK2 expression and ccRCC prognosis was evaluated with univariate and multivariate Cox proportional hazard models. The changes of cell signaling pathways involved in different CHEK2 expression levels were explored with gene set variation analysis (GSVA). The correlation between CHEK2 and immune cell infiltration as well as immune checkpoint molecular expression was analyzed. 【Results】 CHEK2 expression was significantly higher in ccRCC tissues than in normal tissues (P<0.01). Higher level of CHEK2 was significantly associated with higher T stage of ccRCC (P<0.01). Kaplan-Meier analysis showed overall survival (OS) of patients with high CHEK2 expression were notably decreased (P<0.001). Univariate and multivariate analyses revealed CHEK2 expression as an independent risk factor of survival (HR=1.950, 95%CI: 1.490-2.570, P<0.001; HR=1.588, 95%CI: 1.185-2.127, P=0.002). GSVA showed that CHEK2 was involved in the following pathways: proximal tubule bicarbonate reclamation, propanoate metabolism, limonene and pinene degradation, fatty acid metabolism, primary immunodeficiency, systemic lupus erythematosus, p53 signaling pathway, homologous recombination, DNA replication and mismatch repair. Correlation analysis suggested that CHEK2 was associated with increased infiltration of multiple immune cells in ccRCC and upregulation of various immune checkpoint molecules. 【Conclusion】 The high level of CHEK2 in ccRCC is an independent predicting factor for poor prognosis. It is probably involved in regulating related events of tumor immune infiltration and may become a new target for ccRCC therapy.

Correlation between CD10,CA9,CD133 and prognosis of mccRCC treated with sorafenib or sunitinib as first-line therapy / 现代泌尿外科杂志

【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ2=6.241,P=0.012),lymph node metastasis (χ2=5.952,P=0.015),and the number of metastatic organs ≥2 (χ2=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.

Efficacy of adjuvant targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma with tumor thrombus (nccRCC-VTT) / 中华泌尿外科杂志

Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.

Safety and prognostic analysis of partial nephrectomy for cT 1N 0M 0 non-clear renal cell carcinoma with high grade malignancy / 中华泌尿外科杂志

Objective:To investigate the safety and prognosis of partial nephrectomy (PN) in the treatment of highly malignant non-clear renal cell carcinoma (nccRCC).Methods:Clinical data of 47 patients with cT 1N 0M 0 high malignant nccRCC treated in Changhai Hospital from March 2016 to March 2022 were retrospectively analyzed. All patients received PN. There were 34(72.3%) males and 13(27.7%) females. The mean age was (53.5±15.0) years, and average BMI, was(23.7±3.4)kg/m 2.The maximum tumor diameter was (29.8±12.6) mm, and R. E.N.A.L. score was 7(5-9), with 37(78.7%) cases of T 1a and 10(21.3%) cases of T 1b. The mean estimated glomerular filtration rate (eGFR) before surgery was (96.3±25.5) ml/ (min·1.73m 2). All patients underwent PN, including 1 patient (2.1%) undergoing open surgery, 29 patients (61.7%) undergoing laparoscopic surgery, and 17 patients (36.2%) undergoing robotic surgery. There were a total of 22(46.8%) cases of papillary cell carcinoma(pRCC)type Ⅱ, 4(8.5%) cases of collecting duct carcinoma (cdRCC), 9(19.1%) cases of MiT family translocated renal cell carcinoma (tRCC), 5(10.6%) cases of mucoid tubular and spindle cell carcinoma (mtSCC)and 7(14.9%) cases of unclassified renal cell carcinoma (uRCC). The surgical conversion rate, positive margin rate, operative time, intraoperative blood loss, complications, and postoperative hospital stay were analyzed. Preoperative and postoperative eGFR were analyzed, and overall survival (OS) and cancer specific survival (CSS) were calculated. Results:All the operations were successfully completed. No radical operation or open operation was performed, with operation time of(100±60) min and intraoperative blood loss of(100±59) ml. There were no intraoperative complication and 1 case (2.1%) suffered from postoperative complication. Postoperative hospital stay were 5 (4-6) days. The mean eGFR after surgery was (86.5±27.1) ml/(min·1.73m 2), and the difference was statistically significant ( P=0.041). In this study, the mean follow-up time was (45.7±20.9)months, and no adjuvant therapy was used after surgery. During the follow-up period, 2 patients died, who all of them were kidney cancer-related death, and both OS and CSS were 95.7% (45/47). Conclusions:PN is safe, feasible and has a good prognosis in the treatment of high malignant T 1 nccRCC. For tumors with clear imaging boundaries and complete envelope, complete tumor resection is more likely, postoperative follow-up should be strict, and no remedial radical or systemic treatment was required.

Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.@*METHODS@#In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC were analyzed at 24, 48 and 72 h by MTT assay. The protein expression levels of ADAMTS18 gene, p65, phosphorylation p65 (pp65), AKT, phosphorylation AKT (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/L) treatment were examined by Western blotting. Real-time PCR and methylation specific PCR (MSP) were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment (10 μ mol/L).@*RESULTS@#Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose- and time-dependent manner (P<0.01). Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment, accompanied by down-regulation of nuclear factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/AKT common related protein MMP-2. With ADAMTS18 gene overexpressed, the expression levels of p65, AKT and MMP2 were downregulated, of which were conversely up-regulated in silenced ADAMTS18 (sh-ADAMTS18). The expression of pp65, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).@*CONCLUSIONS@#Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.

MiR-744-5p inhibits the proliferation, invasion, and migration of clear-cell renal cell carcinoma cells by targeting CCND1 / 南方医科大学学报

OBJECTIVE@#To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).@*METHODS@#We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.@*RESULTS@#MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).@*CONCLUSION@#MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.

Cost-effectiveness analysis of nivolumab in the second-line treatment of metastatic clear cell renal cell carcinoma / 中国药房

OBJECTIVE To ev aluate the economical efficiency of nivolumab versus everolimus in the second-line treatment of metastatic clear cell renal cell carcinoma. METHODS From the perspective of China ’s health system ，cost-effectiveness analysis of the two therapies was carried out by developing a three-state partitioned survival model. The clinical parameters were from the updated CheckMate 025 study，and the cost and health utility were from relevant websites and published literatures. The model adopted a 2-week cycle and a lifetime research time. The robustness of the results was verified by sensitivity analysis. The economical efficiency of two therapy schemes were evaluated in the scenario of model simulation time of 80 months and charitable drug donation scheme. RESULTS The results of basic analysis showed that compared with everolimus ，the incremental cost-effectiveness ratio （ICER）of nivolumab was 586 982.60 yuan/quality-adjusted life year （QALY），which was far higher than 3 times of China ’s per capita gross domestic product （GDP）in 2020. The results of single-factor sensitivity analysis showed that the 3 parameters that had the greatest impact on the economic evaluation results were the cost of nivolumab ，the utility value of nivolumab group and everolimus group in progressive disease state. The results of probability sensitivity analysis verified the robustness of the basic analysis results. Results of scenario analysis showed that in the first scenario analysis ，in which model simulation time lasted for 80 months，ICER of nivolumab was 417 204.52 yuan/QALY；in the second scenario analysis ，in which nivolumab charitable drug donation program for low-income people was considered ，ICER of nivolumab was 124 988.58 yuan/QALY. CONCLUSIONS Under the threshold of 1-3 times of China ’s per capita GDP in 2020，compared with everolimus ，it is not economical to use nivolumab as the second-line treatment for metastatic clear cell renal cell carcinoma ； nivolumab is economical when considering its charitable drug donation program for low-income people.

Mechanism of B7-H3 molecule in renal clear cell carcinoma cell (786-O) metastasis / 中华微生物学和免疫学杂志

Objective:To investigate the effects of B7-H3 molecule on clear cell renal cell carcinoma (786-O) metastasis.Methods:Lentiviral transfection method was used to construct 786-O cells stably expressing low level of B7-H3 (shB7-H3 group) and a negative control cell line (shNC group). RT-qPCR, flow cytometry and Western blot were used to assess the efficiency of lentiviral transfection. CCK-8 method was used to detect the proliferation of 786-O cells in the two groups. Flow cytometry was performed to detect the changes in cell cycle. Cell scratch test and Transwell assay were used to detect the differences in cell migration and invasion. Western blot was used to detect the expression of marker proteins in the process of epithelial-mesenchymal transition (epithelial-mesenchymal transition, EMT). Changes in the expression of chemokines and their receptors were analyzed by flow cytometry and RT-qPCR. Effects of anti-CCL4 antibody on cell migration and invasion were analyzed by Transwell assay.Results:Flow cytometry showed that 786-O cells highly expressed B7-H3 molecules and the lentiviral transfection method successfully constructed the cell line with lower expression of B7-H3 (786-O-shB7-H3) and control cell line (786-O-shNC). B7-H3 molecule had no significant effect on the proliferation of 786-O cells. No significant difference in cell cycle was found between the two groups. Compared with 786-O-shNC cells, the migration and invasion ability of 786-O-shB7-H3 cells was suppressed. Moreover, the expression of EMT-related marker proteins (fibronectin and N-cadherin) was reduced and the expression of E-cadherin was increased in 786-O-shB7-H3 cells. The expression of CCL4 and its receptor CCR5 in the shB7-H3 group was lower than that in the shNC group. After intervention with anti-CCL4 antibody, the migration and invasion ability of 786-O-shNC cells was reduced, while that of 786-O-shB7-H3 cells had no significant change.Conclusions:Knocking down the expression of B7-H3 molecule had no significant effect on the proliferation of 786-O cells, but could affect the EMT process of 786-O cells and reduce tumor migration and invasion ability, thereby inhibiting tumor progression.

Research Progress of CircRNAs Regulating Biological Behavior of Clear Cell Renal Cell Carcinoma / 肿瘤防治研究

Renal cell carcinoma is one of the ten multiple cancers, and its incidence rate and mortality rate have been increasing in more than 20 years. Clear cell renal cell carcinoma (ccRCC) is the most common histopathological subtype. Cyclic ribonucleic acids (circRNAs) are noncoding ribonucleic acids, which are widely distributed with diverse cellular functions and have organ- and tissue-specific expression patterns. Recent studies have shown that circRNAs are abnormally expressed in ccRCC and play an important role in the occurrence and development of ccRCC. However, there are few researches and related mechanisms of circRNAs regulating the biological behavior of ccRCC. Therefore, the paper mainly describes the research progress of circRNAs regulating the biological behavior of ccRCC and discusses its potential as a biomarker for early diagnosis and prognosis of ccRCC and targeted therapy.

The biology, function, and applications of exosomes in cancer

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.

SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy characterized by a poor prognosis. Suppressor of variegation 3-9 homolog 1 (

Pancreatic collision tumor: mucinous cystadenoma and celar cell renal cell carcinoma metastasis

We present a clinical, radiological, surgical, and pathological correlation case of a 49-year-old woman with a prior nephrectomy due to a clear cell renal cell carcinoma, who was then diagnosed with a multilocular cystic lesion in the pancreatic tail after a routine ultrasound. Computed tomography and magnetic resonance cholangiopancreatography showed a multilocular cystic lesion with a hypervascular wall nodule in the pancreas. The patient underwent a distal pancreatectomy and had a final diagnosis of pancreatic mucinous cystadenoma with an associated component of clear cell renal cell carcinoma (collision tumor of the pancreas). (AU)

Involvement of the TNF-α Pathway in TKI Resistance and Suggestion of TNFR1 as a Predictive Biomarker for TKI Responsiveness in Clear Cell Renal Cell Carcinoma

10% of labeled tumor cells) of TNF receptor 1 (TNFR1), the protein product of TNFRSF1A gene, was correlated with sarcomatoid dedifferentiation and was an independent predictive factor of clinically unfavorable response and shorter survivals in separated TKI-treated ccRCC cohort.CONCLUSION: TNF-α signaling may play a role in TKI resistance, and TNFR1 expression may serve as a predictive biomarker for clinically unfavorable TKI responses in ccRCC.