Understanding m6A changes in chromophobe renal cell carcinoma and predicting patient outcomes survival.

N6-methyladenosine (m6A) is a prevalent mRNA modification known for its implications in various cancer types, yet its role in chromophobe renal cell carcinoma (chRCC) remains largely unexplored. In this study, we performed m6A-SEAL-seq and RNA-seq analyses on tissues from three chRCC subjects, aiming to uncover m6A alterations in chRCC. Our findings revealed reduced expression levels of four m6A regulators in chRCC tissues and highlighted differences in m6A levels compared to normal tissues. Furthermore, we identified specific genes and cancer-related pathways affected by these differences, including notable candidates like NOTCH1 and FGFR1, implicated in chRCC development. Additionally, we developed a predictive model based on the expression level of m6A associated genes, demonstrating promising prognostic capabilities for patient survival prediction. Overall, our study provides valuable insights into the role of m6A in chRCC and its potential as a prognostic indicator.

A nomogram predicting intraoperative adverse events during minimally invasive radical nephrectomy and thrombectomy.

BACKGROUND: To define the incidence and independent predictive factors of intraoperative adverse events (IOAEs) after minimally invasive radical nephrectomy and thrombectomy (RNAT) and to determine the impact of intraoperative adverse events on oncological outcomes. PATIENTS AND METHODS: A total of 294 patients underwent minimally invasive RNAT from January 2010 to December 2023 in our center were included. IOAEs are defined as any deviation from the normal surgical procedure during the operation course. Multivariate logistic regression analysis was performed to identify the independent predictive factors of IOAEs. The Kaplan-Meier curves was used to compare overall survival and cancer-specific survival between patients with IOAEs or not. RESULTS: Seventy-four IOAEs occurred in 57 of 294 patients (19.4%) and the most frequent IOAEs were conversion to open surgery (42/74, 56.7%), followed by excessive hemorrhage (20/74, 27.0%). In multivariate logistic analysis, side (OR 0.0929; 95%Cl 0.0367-0.2160; p < 0.001), operation approach (OR 0.1762; 95%Cl 0.06828-0.4109; p < 0.001), and Mayo grade (OR 6.321; 95%Cl 3.846-11.13; p < 0.001) were independent predictive predictors of IOAEs during minimally invasive RNAT. IOAEs (OR 2.713; 95%Cl 1.242-5.897; p = 0.012) was an independent risk factor of the occurrence of postoperative complications. Between the patients with IOAEs or not, neither overall survival (OS) nor cancer-specific survival (CSS) showed statistical differences. Patients with postoperative complications show shorter OS and CSS. CONCLUSION: We found that the independent predictive factors of  minimally invasive RNAT were side, operation approach and Mayo grade, and it is a risk factor of the occurrence of postoperative complications. In addition, the occurrence of IOAEs had no effect on long-term oncological outcomes.

[Predicting the 3-year tumor-specific survival in patients with T3a non-metastatic renal cell carcinoma].

OBJECTIVE: To predict the 3-year cancer-specific survival (CSS) of patients with non-metastatic T3a renal cell carcinoma after surgery. METHODS: A total of 336 patients with pathologically confirmed T3a N0-1M0 renal cell carcinoma (RCC) who underwent surgical treatment at the Department of Urology, Peking University Third Hospital from March 2013 to February 2021 were retrospectively collected. The patients were randomly divided into a training cohort of 268 cases and an internal validation cohort of 68 cases at an 4 ∶ 1 ratio. Using two-way Lasso regression, variables were selected to construct a nomogram for predicting the 3-year cancer-specific survival (CSS) of the patients with T3aN0-1M0 RCC. Performance assessment of the nomogram included evaluation of discrimination and calibration ability, as well as clinical utility using measures such as the concordance index (C-index), time-dependent area under the receiver operating characteristic curve [time-dependent area under the curve (AUC)], calibration curve, and decision curve analysis (DCA). Risk stratification was determined based on the nomogram scores, and Kaplan-Meier survival analysis and Log-rank tests were employed to compare progression-free survival (PFS) and cancer-specific survival (CSS) among the patients in the different risk groups. RESULTS: Based on the Lasso regression screening results, the nomogram was constructed with five variables: tumor maximum diameter, histological grading, sarcomatoid differentiation, T3a feature, and lymph node metastasis. The baseline data of the training and validation sets showed no statistical differences (P>0.05). The consistency indices of the column diagram were found to be 0.808 (0.708- 0.907) and 0.903 (0.838-0.969) for the training and internal validation sets, respectively. The AUC values for 3-year cancer-specific survival were 0.843 (0.725-0.961) and 0.923 (0.844-1.002) for the two sets. Calibration curves of both sets demonstrated a high level of consistency between the actual CSS and predicted probability. The decision curve analysis (DCA) curves indicated that the column diagram had a favorable net benefit in clinical practice. A total of 336 patients were included in the study, with 35 cancer-specific deaths and 69 postoperative recurrences. According to the line chart, the patients were divided into low-risk group (scoring 0-117) and high-risk group (scoring 119-284). Within the low-risk group, there were 16 tumor-specific deaths out of 282 cases and 36 postoperative recurrences out of 282 cases. In the high-risk group, there were 19 tumor-specific deaths out of 54 cases and 33 post-operative recurrences out of 54 cases. There were significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) between the low-risk and high-risk groups (P < 0.000 1). CONCLUSION: A nomogram model predicting the 3-year CSS of non-metastatic T3a renal cell carcinoma patients was successfully constructed and validated in this study. This nomogram can assist clinicians in accurately assessing the long-term prognosis of such patients.

Renal Angiomyolipoma with Tumor Thrombus in the Inferior Vena Cava and Right Atrium Accompanied by Renal Cell Carcinoma: A Case Report.

Background: Renal angiomyolipoma (AML) without local invasion is generally considered benign. However, it may extend to the renal sinus, even the renal vein, or the inferior vena cava (IVC). In patients with non-tuberous sclerosis complex, coexistence of renal cell carcinoma (RCC) and renal AML is uncommon. Case presentation: A 72-year-old woman was incidentally found to have a solitary right renal mass with an IVC thrombus extending into the right atrium during a routine health checkup. Robot-assisted laparoscopic radical nephrectomy and thrombectomy were successfully performed through adequate preoperative examination and preparation. Two tumor lesions were found and pathologically confirmed as renal AML and RCC, and the tumor thrombus was derived from the renal AML. During the one-year follow-up period, no signs of recurrence or metastatic disease were observed. Conclusions: Renal AML with a tumor thrombus in the IVC and right atrium accompanied by RCC may occur, although rarely. In clinical practice, if preoperative manifestations differ from those of common diseases, rare diseases must be considered to avoid missed diagnoses. In addition, adequate examination and multidisciplinary discussions before making a diagnosis are necessary. For a level 4 tumor thrombus with no infringement of the venous wall, adoption of robot-assisted minimally invasive surgery, without extracorporeal circulation technology, is feasible.

Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

OBJECTIVES: To investigate perioperative clinicopathological predictors and establish a predictive nomogram for survival in patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy. METHODS: Patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy were included in the study between January 2014 and June 2020. Cox regression analysis was used for univariate and multivariate survival analyses. A predictive nomogram for survival was established and internally validated using bootstrap resampling method. RESULTS: A total of 228 patients were enrolled in this study. The median age was 60 years (interquartile range 53-66 years), consisting of 174 (76.3%) males and 54 (23.7%) females. The median follow-up time was 17.5 months (range 1-74 months), 26.8% (61 of 228) patients died of all causes. In multivariable analysis, hemoglobin less than the lower limit of normal (hazard ratio 1.73; 95% confidence interval 1.01-2.96; P = 0.045), sarcomatoid feature (hazard ratio 3.67; 95% confidence interval 1.97-6.82; P < 0.001), perirenal fat invasion (hazard ratio 1.80; 95% confidence interval 1.05-3.09; P = 0.033), histological subtype (hazard ratio 2.74; 95% confidence interval 1.39-5.41; P = 0.004), and metastasis at surgery (hazard ratio 1.71; 95% confidence interval 1.01-2.90; P = 0.047) were independently associated with overall survival. The result of internal validation presented that the predictive performance of the nomogram for survival measured by C-index was 0.77. CONCLUSIONS: We developed a predictive nomogram with well-internal validation for survival in patients with renal cell carcinoma and venous tumor thrombus, which can greatly promote risk stratification and treatment planning.

Preliminary experience of oblique occlusion technique in robot-assisted infrahepatic inferior vena cava thrombectomy: step-by-step procedures and short term outcomes.

BACKGROUND: We aimed to compare the oncological outcomes between the oblique occlusion technique and the traditional technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) thrombectomy, and to explore the safety and effectiveness of the oblique occlusion technique. METHODS: Overall, 21 patients with renal cell carcinoma (RCC) and IVC tumor thrombus (TT) were admitted to our hospital from August 2019 to June 2020. All the patients underwent RARN with IVC thrombectomy, of which the IVC oblique occlusion technique was used in 11 patients and traditional occlusion technique was used in 10 patients. The oblique occlusion technique refers to oblique blocking from the upper corner of the right renal vein to the lower corner of the left renal vein using a vessel tourniquet or a vessel clamp (left RCC with IVCTT as an example). RESULTS: Compared with patients in the traditional group, those in the oblique group had lower serum creatinine at follow-up (3 month) (95 ± 21.1 vs. 131 ± 30.7 µmol/L, P = 0.03). There was no significant difference in operation time [149 (IQR 143-245) min vs. 148 (IQR 108-261) min, p = 0.86], IVC clamping time [18 (IQR 12-20) min vs. 20 (IQR 14-23) min, p = 0.41], and estimated intraoperative blood loss [300 (IQR 100-800) mL vs. 500 (IQR 175-738) mL, p = 0.51] between both groups. During a 16-month (range, 15-23 months) follow-up period, two cases progressed in the oblique group and three cases progressed in the traditional group. CONCLUSIONS: The modified IVC oblique occlusion technique procedure is relatively safe and effective in RARN with IVC thrombectomy. The IVC oblique occlusion technique may play a role in the protection of renal function.

Outcomes of renal cell carcinoma with associated venous tumor thrombus: experience from a large cohort and short time span in a single center.

BACKGROUND: The surgical management and outcomes of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) have been reported in limited sample size, and there remain discrepancies over the factors that influence oncologic outcomes after radical nephrectomy with thrombectomy (RNTE). The aim of the study was to analyze the outcomes of the patients with RCC with VTT in our institution and identify the independent prognostic factors. METHODS: Patients with RCC with VTT were enrolled for the study from February 2015 to December 2018. All patients underwent RNTE. Clinical data were compared using Mann-Whitney U test and the chi-square test for continuous and categorical variables respectively. Survival analysis was estimated using the Kaplan-Meier method. Univariable and multivariable survival analyses were performed using Cox regression model. RESULTS: 121 patients (91 men & 30 women) were identified with a median age of 60 years. VTT level was 0 in 25 patients, I in 20, II in 50, III in 12 and IV in 14. The median follow-up time was 24 months. During the follow-up period, 51 (42%) patients died and 69 (57%) patients experienced recurrence or metastasis. The 3-year and 5-year over-all survival (OS) were 58 and 39%. Among the several factors examined, positive lymph node (P = 0.016), metastasis at surgery (P = 0.034), tumor necrosis (P = 0.023) and sarcomatoid differentiation (P < 0.001) were demonstrated as independent significant risk factors on multivariable analysis. CONCLUSION: The OS was poor for patients with RCC with VTT. Rather than VTT level, positive lymph node, metastasis at surgery, tumor necrosis and sarcomatoid differentiation were independent prognostic predictors.

Prognostic Value of Positive Lymph Nodes in Patients with Renal Cell Carcinoma and Tumor Thrombus Undergoing Nephrectomy and Thrombectomy.

INTRODUCTIONS: The objective of this study was to determine the prognostic value of positive lymph nodes (LNs) in patients with renal cell carcinoma (RCC) and tumor thrombus (TT) and to explore risk factors predicting LNs metastasis. METHODS: We retrospectively analyzed 216 patients with RCC and TT treated at a single institution from January 2015 to December 2019. Overall survival (OS) and progression-free survival (PFS) was estimated using the Kaplan-Meier curves divided by pathological LN status. Associations between clinicopathological features and survival outcomes were evaluated using Cox regression models. Logistic regression model was performed to determine risk factors associated with LN metastasis. RESULTS: We identified 216 patients with RCC and TT including 85 (39.4%) who did and 131 (60.6%) who did not undergo lymph node dissection. Pathologically positive LNs were found in 18 (8.3%) cases. pN1 had significant worse OS (median: 21 vs. 41 and 56 months, p < 0.001) and PFS (median:14 vs. 29 and 33 months, p < 0.001) than pN0 and pNx respectively. However, survival outcomes of OS and PFS were similar between pNx-0/M1 and pN1/M0 group and between 1- and ≥2-node-positive group. Non-CCRCC (p = 0.001), sarcomatoid differentiation (p < 0.001), and pathologically positive LNs (p = 0.025) were independent prognostic predictors predicting worse OS while distance metastasis (p = 0.009), non-CCRCC (p = 0.023), necrosis (p = 0.014), sarcomatoid differentiation (p = 0.003), and pathologically positive LNs (p = 0.007) were independent prognostic indicators predicting worse PFS. Clinically positive LNs (p = 0.014) and sarcomatoid differentiation (p = 0.009) were predictors of positive LNs. CONCLUSIONS: LNs metastasis independently associated with worse survival outcomes in RCC and TT populations, with similar survival outcomes compared to distance metastasis. Therefore, more accurate risk stratification is warranted for guiding postoperative surveillance and adjuvant therapy.

Renal cell carcinoma with tumor thrombus growing against the direction of venous return: an indicator of complicated surgery and poor prognosis.

PURPOSE: To explore the effect of tumor thrombus growing against the direction of venous return (GADVR) tumor thrombus on the choice of surgical approach, the impact on the complexity of the surgery and the prognosis. METHODS: We retrospectively analyzed the clinicopathological data of 213 patients, who underwent surgery in a single center of Peking University Third Hospital between January 2016 and June 2020. For right renal cell carcinoma (RCC) and venous tumor thrombus (VTT), imaging revealed a filling defect in the left renal vein, which was significantly enhanced in enhanced imaging, suggesting that the tumor thrombus grew against the direction of venous return into the left renal vein. For left RCC and VTT, at least one of the left renal vein branches has tumor thrombus. The branches include the left adrenal vein, the left gonadal vein (testicular vein or ovarian vein), and the left ascending lumbar vein. The patients were divided into two groups according to whether they were GADVR tumor thrombus, and we compare the clinicopathological characteristics of GADVR tumor thrombus and non-GADVR tumor thrombus. Univariate and multivariate Cox regression analyses were performed to explore the risk factors that affect the prognosis of patients with RCC and VTT. Kaplan-Meier plots were conducted to evaluate the effect of GADVR on progression-free survival (PFS). RESULTS: Compared with non-GADVR tumor thrombus, patients with GADVR tumor thrombus had a higher proportion of open surgery (76.2% vs. 52.1%, P = 0.035), a higher proportion of tumor thrombus adhering to the inferior vena cava (IVC) vessel wall (81% vs. 45.8%, P = 0.002), a higher proportion of segmental resection of the IVC vessel wall (61.9% vs. 15.6%, P < 0.001); higher preoperative serum creatinine value (110.0 µmol/L vs. 91.0 µmol/L, P = 0.015), a higher proportion of tumor thrombus combined with bland thrombus (non-tumor thrombus) (57.1% vs. 19.8%, P < 0.001). In terms of surgical complexity, patients with GADVR tumor thrombus had a longer median operation time (379 min vs. 308 min, P = 0.038), more median surgical blood loss (1400 mL vs. 600 mL, P = 0.018), and more postoperative complications (52.4% vs. 30.7%, P = 0.045). Multivariate Cox regression analysis showed that GADVR tumor thrombus, symptoms, postoperative serum creatinine, distant metastasis, sarcomatoid feature, pathological type, lymph node dissection were independent risk factors for PFS. Patients with GADVR tumor thrombus's median survival time was 14.0 months, while patients with non-GADVR tumor thrombus were 32.0 months (P = 0.016). GADVR tumor thrombus is an independent risk factor for PFS in patients with RCC and VTT. CONCLUSION: GADVR tumor thrombus is a characteristic feature of tumor thrombus, with an incidence of 9.9%. It has a higher proportion of open surgery and higher surgical complexity, which is an independent risk factor for PFS.

Inferior vena cava interruption in renal cell carcinoma with tumor thrombus: surgical strategy and perioperative results.

BACKGROUND: To analyze the influence of inferior vena cava (IVC) interruption for perioperative and oncological results in patients with renal cell carcinoma and tumor thrombus and summarize the surgical strategies of IVC interruption for different situations. METHODS: We retrospectively analyzed the clinical and pathological data of 103 patients in our center. Patients were divided into two groups with 32 cases (31.1%) underwent IVC interruption (Group 1) while 71 cases (68.9%) did not. For comparison of continuous variables, the Mann-Whitney U test was used. For comparison of categorical variables, Chi-square tests were used. A propensity score based matching method was used to eliminate possible bias. Kaplan-Meier plots were performed to evaluate the influence of IVC interruption on overall survival and cancer specific survival. All the statistical analyses were performed using SPSS 24. A P value < 0.05 was considered statistically significant. RESULTS: Among the 32 patients who underwent IVC interruption, the median age was 61 years and the median tumor size was 7.7 cm. There were 28 males and 23 tumors were on the right side. We successfully matched 29 patients who underwent IVC interruption to 29 patients without this procedure in 1:1 ratio. No significant differences existed in baseline characteristics between the groups. The comparison of perioperative data showed that patients who underwent IVC interruption had significantly longer median postoperative hospital stays (13 vs 9 days, P = 0.022) and a higher overall postoperative complication rate (79.3 vs 51.7%, P = 0.027). According to the side and shape of tumor thrombus, it could be divided into four categories. There were 15 cases (46.9%) with right filled-type tumor thrombus (RFTT), 8 cases (25.0%) with right non-filled-type tumor thrombus (RNFTT), 1 case (3.1%) with left filled-type tumor thrombus (LFTT) and 8 cases (25.0%) with left non-filled-type tumor thrombus (LNFTT). According to different categories, different surgical procedures were adopted. CONCLUSIONS: IVC interruption will increase the incidence of overall postoperative complications, but not the risk of major postoperative complications. Tumor thrombus should be divided into four categories, and different sides and shapes of renal tumor thrombus need different operative procedure of IVC interruption.

Genomic Alterations of Renal Cell Carcinoma and Clinical Implications in the Chinese Population.

BACKGROUND The aim of this study was to investigate the genomic alterations of renal cell carcinoma (RCC) in Chinese patients and to evaluate the correlations between significantly mutated genes and tumor mutation burden (TMB) levels in RCC. MATERIAL AND METHODS Two batch of specimens were collected from patients with RCC. Cohort 1 enrolled 17 RCC patients. Specimens and clinicopathological data were collected and the duration of disease-free survival were evaluated with a follow-up from 2 weeks to longer than 1 year. Cohort 2 collected 70 clear cell RCC (ccRCC) tissues and blood specimens. Next-generation sequencing were used to detect the genomic variations in those specimens in both cohorts and TMB in cohort 2. Clinicopathological features of the 2 cohorts were collected and the χ² test or Fisher's exact test was used for categorical variables stratified by TMB values. RESULTS Our present study demonstrated that the top 3 most frequent aberrated genes in Chinese ccRCC patients were ABCB1, UGT1A1, and VHL, with percentages of 50.00%, 42.86%, and 34.52% respectively. And only 1 gene, which was ABCB1, showed statistically significant difference (P=0.047) stratified by TMB levels. In addition, 6 oncogenic pathways were involved in ccRCC cases in the 2 cohorts. Only 5 out of the 8 most common altered genes of RCC from COSMIC or TCGA databases were detected in our study. CONCLUSIONS The genomic alterations of Chinese RCC patients were different from that in TCGA and COSMIC. No significant genomic alterations were found correlating to TMB levels in ccRCC. Non-silent mutation of VHL may be a predictor for the outcome of ccRCC treated with axitinib.

High-efficiency secretory expression of human neutrophil gelatinase-associated lipocalin from mammalian cell lines with human serum albumin signal peptide.

Human neutrophil gelatinase associated lipocalin (NGAL) is a secretory glycoprotein initially isolated from neutrophils. It is thought to be involved in the incidence and development of immunological diseases and cancers. Urinary and serum levels of NGAL have been investigated as a new biomarker of acute kidney injury (AKI), for an earlier and more accurate detection method than with creatinine level. However, expressing high-quality recombinant NGAL is difficult both in Escherichia coli and mammalian cells for the low yield. Here, we cloned and fused NGAL to the C-terminus of signal peptides of human NGAL, human interleukin-2 (IL2), gaussia luciferase (Gluc), human serum albumin preproprotein (HSA) or an hidden Markov model-generated signal sequence (HMM38) respectively for transient expression in Expi293F suspension cells to screen for their ability to improve the secretory expression of recombinant NGAL. The best results were obtained with signal peptide derived from HSA. The secretory recombinant protein could react specifically with NGAL antibody. For scaled production, we used HSA signal peptide to establish stable Chinese hamster ovary cell lines. Then we developed a convenient colony-selection system to select high-expression, stable cell lines. Moreover, we purified the NGAL with Ni-Sepharose column. The recombinant human NGAL displayed full biological activity. We provide a method to enhance the secretory expression of recombinant human NGAL by using the HSA signal peptide and produce the glycoprotein in mammalian cells.

Transient expression of Fc-fused human glycoprotein 130 in Expi293F suspension cells.

Human glycoprotein 130 (gp130) is a signal-transducing receptor for interleukin 6 (IL-6), whose signaling plays a critical role in chronic inflammation and cancer. The soluble form of gp130 specifically inhibits IL-6 trans-signaling. However, achieving high-level expression of a large glycoprotein such as gp130 is difficult. Here, we designed and constructed one Fc-gp130-pcDNA mammalian expression vector, with the mouse IgG2a Fc fragment added to the N-terminus of human gp130, which greatly increased the secretion of recombinant gp130 protein from Expi293F suspension cells. Recombinant fusion Fc-gp130 was easily and efficiently purified from the supernatant of transfected cells by one-step affinity chromatography. Moreover, Fc-gp130 could automatically form dimers by the disulfide bond. Fc-gp130 was confirmed as a more efficient IL-6 trans-signaling blocker by its higher biological activity against signal transducer and activator of transcription 3 (STAT3). This purified active Fc-gp130 could be used to develop valuable therapeutic agents against inflammatory diseases and cancers.

Sotos syndrome treated with traditional Chinese medicine and rehabilitation: Case report.

RATIONALE: Sotos syndrome is an congenital overgrowth syndrome characterized by the primary features including overgrowth, distinctive facial features, learning disability, and accompanied with various second features. NSD1 deletion or mutation is a major pathogenic cause. Although there are some reports on treatment of this disease worldwide, less cases under treatment have been published in China. PATIENT CONCERNS: A 1-year-old boy had macrocephaly, gigantism, excessive high body height, a particular face and delayed development, with a pathogenic gene of NSD1 (NM_022455.5:c.3536delA in exon 5). DIAGNOSIS AND INTERVENTIONS: The child was definitely diagnosed as Sotos syndrome and have 3 months' combination treatment of traditional Chinese medicine and rehabilitation. OUTCOMES: The child made a great progress in global development. LESSONS: This case firstly describes the traditional Chinese medicine and rehabilitation to treat Sotos syndrome in China. There is no radical cure, but our therapy could improve the prognosis and the life quality of the patient. Therefore, this case provides a reference to the clinical treatment of Sotos syndrome.

ATAD2 promotes glycolysis and tumor progression in clear cell renal cell carcinoma by regulating the transcriptional activity of c-Myc.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urogenital tract. Given that ccRCC is often resistant to radiotherapy and traditional chemotherapy, the clinical treatment of patients with ccRCC remains a challenge. The present study found that ATAD2 was significantly upregulated in ccRCC tissues. In vitro and in vivo experiments showed that the inhibition of ATAD2 expression mitigated the aggressive phenotype of ccRCC. ATAD2 was also associated with glycolysis in ccRCC. Interestingly, we found that ATAD2 could physically interact with c-Myc and promote the expression of its downstream target gene, thereby enhancing the Warburg effect of ccRCC. Overall, our study emphasizes the role of ATAD2 in ccRCC. The targeted expression or functional regulation of ATAD2 could be a promising method to reduce the proliferation and progression of ccRCC.

L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma.

The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-derived paracrine factors. Renal cell carcinoma (RCC) is among the most prevalent tumors of the urinary system, and the formation of venous tumor thrombus (VTT) is a characteristic feature of RCC. We observed high expression of L1CAM in the VTT with vessel wall invasion. L1CAM promotes the adhesion, migration, and invasion ability of RCC and enhances metastasis by interacting with ITGA5, which elicits activation of signaling downstream of integrin α5ß1. L1CAM promotes ADAM17 transcription to facilitate transmembrane ectodomain cleavage and release of soluble L1CAM. In response to soluble L1CAM, vascular endothelial cells release several cytokines and chemokines. Endothelial-derived CXCL5 and its receptor CXCR2 promote the migration and intravasation of RCC toward endothelial cells suggesting that crosstalk between endothelial cells and tumor cells has a direct guiding role in driving the metastatic spread of RCC. LICAM plays a crucial role in the invasive ability of RCC, and regulation of L1CAM expression may contribute therapeutically to preventing RCC progression.

TPM2 attenuates progression of prostate cancer by blocking PDLIM7-mediated nuclear translocation of YAP1.

BACKGROUND: Prostate cancer (PCa) is a common malignant tumor of the genitourinary system. Clinical intervention in advanced PCa remains challenging. Tropomyosins 2 (TPM2) are actin-binding proteins and have been found as a biomarker candidate for certain cancers. However, no studies have explored the role of TPM2 in PCa and its regulatory mechanism. METHODS: TPM2 expression was assessed in Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) PCa patient dataset. The effect of TPM2 on PCa progression was assessed in vitro and in vivo by quantifying proliferation, migration, invasion and tumor growth assays, and the mechanism of TPM2 in PCa progression was gradually revealed by Western blotting, immunoprecipitation, and immunofluorescence staining arrays. RESULTS: TPM2 was found to be severely downregulated in tumor tissues of PCa patients compared with tumor-adjacent normal tissues. In vitro experiments revealed that TPM2 overexpression inhibited PCa cell proliferation, invasion and androgen-independent proliferation. Moreover, TPM2 overexpression inhibited the growth of subcutaneous xenograft tumors in vivo. Mechanistically, this effect was noted to be dependent on PDZ-binding motif of TPM2. TPM2 competed with YAP1 for binding to PDLIM7 through the PDZ-binding motif. The binding of TPM2 to PDLIM7 subsequently inhibited the nuclear transport function of PDLIM7 for YAP1. YAP1 sequestered in the cytoplasm phosphorylated at S127, resulting in its inactivation or degradation which in turn inhibited the expression of YAP1 downstream target genes. CONCLUSIONS: This study investigated the role of TPM2, PDLIM7, and YAP1 in PCa progression and castration resistance. TPM2 attenuates progression of PCa by blocking PDLIM7-mediated nuclear translocation of YAP1. Accordingly, targeting the expression or functional modulation of TPM2, PDLIM7, or YAP1 has the potential to be an effective therapeutic approach to reduce PCa proliferation and prevent the progression of castration-resistant prostate cancer (CRPC).

Interfacial Polymerization Produced Magnetic Particles with Nano-Filopodia for Highly Accurate Liquid Biopsy in the PSA Gray Zone.

Magnetic particles are leading separation materials for biological purification and detection. Existing magnetic particles, which almost rely on molecule-level interactions, however, often encounter bottlenecks in highly efficient cell-level separation due to the underestimate of surface structure effects. Here, immune cell-inspired magnetic particles with nano-filopodia (NFMPs) produced by interfacial polymerization for highly efficient capture of circulating tumor cells (CTCs) and further accurate clinical diagnosis of prostate cancer are reported . The unprecedented construction of nano-filopodia on polymer-based magnetic particles is achieved by introducing electrostatic interactions in emulsion interfacial polymerization. Due to the unique nano-filopodia, the NFMPs allow remarkably enhanced CTCs capture efficiency (86.5% ± 2.8%) compared with smooth magnetic particles (SMPs, 35.7% ± 5.7%). Under the assistance of machine learning by combining with prostate-specific antigen (PSA) and free to total PSA (F/T-PSA), the NFMPs strategy demonstrates high sensitivity (100%), high specificity (93.3%), and a high area under the curve (AUC) value (98.1%) for clinical diagnosis of prostate cancer in the PSA gray zone. The NFMPs are anticipated as an efficient platform for CTCs-based liquid biopsy toward early cancer diagnosis and prognosis evaluation.

Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique in Right Nephrectomy and Inferior Vena Cava Tumor Thrombectomy: A Novel Surgical Technique and Long-Term Outcomes from a Large Chinese Center.

Purpose: To explore the safety and effectiveness of the Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique (PREP-IT) in laparoscopic radical nephrectomy (LRN) and inferior vena cave (IVC) tumor thrombectomy for right renal-cell carcinoma (RCC) with level Mayo I to III venous tumor thrombus (VTT). Patients and Methods: From May 2015 to September 2020, 92 patients with right RCC and Mayo I to III VTT were retrospectively reviewed, including 57 patients who underwent retroperitoneal LRN and IVC thrombectomy using PREP-IT, and 35 patients who underwent open surgery. PREP-IT refers to dissecting the retroperitoneum and temporarily placing the right kidney into the abdominal cavity to enlarge the retroperitoneal workspace for a safer and faster IVC operation. Results: Compared with the open surgery group, the PREP-IT group had a larger tumor diameter, while a larger proportion of Mayo I tumor thrombus and smaller maximum tumor thrombus width. Two patients (3.5%) in the PREP-IT group had a history of abdominal surgery. No conversion to open surgery or standard laparoscopic surgery occurred in PREP-IT group. Laparoscopic surgery with PREP-IT was characterized by shorter operative time, less surgical blood loss, shorter postoperative hospital stay, and lower postoperative complication rate. With a 33-month (ranges: 2-86) follow-up time period, the estimated mean overall survival time was 57.2 ± 5.3 and 58.1 ± 71.5 months in the PREP-IT group and open surgery group, respectively. Log-rank test indicated no significant difference between the two groups in terms of overall survival and cancer-specific survival. Conclusions: The PREP-IT is relatively safe and feasible for retroperitoneal LRN with right renal tumor and IVC tumor thrombus, allowing for a large workspace and wide exposure for IVC operations.

Identification of KIF23 as a Prognostic Biomarker Associated With Progression of Clear Cell Renal Cell Carcinoma.

About 3% of adult cancers are caused by renal cell carcinoma (RCC) and its pathogenesis remains elusive. Among RCC, clear cell renal cell carcinoma (ccRCC) is the predominant histological subtype. Resistance to conventional treatments leaves few treatment options for advanced ccRCC. Although the transcriptome profile of primary ccRCC has been comprehensively summarized, the transcriptome profile of metastatic ccRCC is still lacking. In this study we identified a list of metastasis-related genes and constructing a metastasis-associated prognostic gene signature. By analyzing data from GSE85258 and GSE105288 datasets, 74 genes were identified as metastasis-related genes. To construct prognostic features, we downloaded the expression data of ccRCC from the Cancer Genome Atlas (TCGA). Metastasis-associated genes were initially selected through the LASSO Cox regression analysis and 12 metastasis-related were included to construct prognostic model. Transcriptome profile, patient prognosis, and immune cell infiltration characteristics differed between low- and high-risk groups after grouping according to median risk score. Through explored the functions of differentially expressed genes (DEGs) between the two groups. Kinesin family member 23 (KIF23) was identified as a prognostic marker in ccRCC patients. Furthermore, inhibition of KIF23 expression reduced the proliferation, migration and invasion of ccRCC cells. We further demonstrated that KIF23 promote nuclear translocation of ß-catenin in ccRCC cells, which provides novel insight into the functions and molecular machinery of KIF23 in ccRCC.