Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.

Tubulocystic renal cell carcinoma: A case report of rare tumor.

Tubulocystic renal cell carcinoma (RCC) is a rare renal cancer first recognized by the WHO in 2016 as independent disease category, characterized by its typically indolent features and low rates of metastasis. We present a 35-year-old male with tubulocystic RCC diagnosed incidentally on evaluation of flank pain. Magnetic resonance imaging showed Bosniak class 4 renal cyst, although initial computed topography showed a hypodense nonenhancing lesion classified as Bosniak 1 cyst. Patient underwent robotic assisted partial nephrectomy, histopathology confirmed as tubulocystic RCC. This case highlights the importance of considering tubulocystic RCC in the differential diagnoses of renal cysts and other solid renal masses to ensure timely and effective treatment plan.

Surgical Management of Renal Cell Carcinoma: Comparisons of open and laparoscopic approaches.

Objectives: Renal cell carcinoma (RCC) is a leading urological malignancy with an age-standardised incidence rate of 2.5 per 100,000 per year in Oman. Experts are inclined towards the early detection and use of minimally invasive technology for the treatment of RCC. This study aimed report the shifting trend in the clinical presentation and management of RCC in Oman, comparing the outcomes of laparoscopic and open nephrectomy. Methods: This retrospective study included adult RCC patients from Sultan Qaboos University Hospital, Muscat, Oman, diagnosed from 2011-2022. Patient biodata, mode of presentation, diagnostic modality, final histopathology and details of treatment received including the perioperative outcomes were analysed. Results: A total of 56 patients that underwent surgical treatment for RCC, 34 underwent laparoscopic nephrectomy (LN) and 22 underwent open nephrectomy (ON). The mean ages in the LN and ON groups were 53.82 ± 13.44 years and 56.22 ± 15.00 years (P = 0.53), respectively. There were 47 patients of Omani descent and 9 patients were expatiates. The patients' mean tumour size was 6.25 ± 3.16 cm and 9.23 ± 5.20 cm for the LN and ON groups, respectively; 55.35% of the RCC cases were incidentally diagnosed. A trend towards LN was observed. Conclusion: This study found a trend towards early diagnosis of RCC in Oman, with the majority of cancers being discovered incidentally in the studied period. LN is more commonly used in the surgical management of RCC with acceptable morbidity. These trends remain aligned with those found in the global literature on RCC.

Paraneoplastic Syndrome Prevalence and Survival in Racially-Diverse Cohort With Renal Cell Carcinoma.

INTRODUCTION: The prevalence of preoperative paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) is poorly understood. Many laboratory abnormalities representative of PNS have demonstrated prognostic value when incorporated into predictive survival models in RCC. We sought to characterize the relationship between baseline prevalence of PNS with overall survival (OS) and cancer-specific survival (CSS) in RCC patients following nephrectomy. METHODS: Our prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology RCC patients that underwent surgery from 2000 to 2022. Baseline laboratory values within 90 days (closest used) were required. Presence of PNS was defined according to established laboratory cutoffs. Kaplan-Meier curves estimated survival rates, and multivariable Cox proportional hazards models examined the association between PNS with OS and CSS following nephrectomy. RESULTS: 2599 patients were included with listed staging: 1494 Stage I; 180 Stage II; 616 Stage III; 306 Stage IV. Proportion of patients presenting with >1 PNS significantly increased from stage I (31.3%) to stage IV (74.2%) RCC (P < .001). Elevated C-reactive protein was the most prevalent PNS (45.4%). On multivariable analysis, the presence of >1 PNS was associated with higher risk of all-cause (HR 2.09; P < .001) and cancer-specific mortality (HR 2.55; P < .001). The 10-year OS estimates as reported: 65.2% (no PNS), 52.3% (1 PNS), 36.6% (>1 PNS); and 10-year CSS estimates: 88.3% (no PNS), 79.3% (1 PNS), 61.6% (>1 PNS). DISCUSSION: Increased prevalence of PNS in major histology RCC was associated with a significant increase in the risk of all-cause and cancer-specific mortality even when accounting for patient and disease characteristics.

Clinical features and response to immune combinations in patients with renal cell carcinoma and sarcomatoid de-differentiation (ARON-1 study).

Metastatic renal cell carcinoma (mRCC) carrying sarcomatoid features (sRCC) has aggressive biology and poor prognosis. First-line immunotherapy (IO)-based combinations have improved the outcome of clear cell RCC patients, including that of sRCC. Real-world data confirming the adequate first-line management of sRCC is largely lacking. We investigated the clinical features and the outcome of sRCC patients treated with IO-based combinations within the ARON-1 study population (NCT05287464). The primary objective was to define the incidence and baseline clinical characteristics of sRCC compared with non-sRCC patients. The secondary objective was to describe the outcome of sRCC patients based on type of first-line treatment (IO + IO vs. IO + tyrosin kinase inhibitor [TKI]). We identified 1362 mRCC patients with IMDC intermediate or poor risk, 226 sRCC and 1136 non-sRCC. These two subgroups did not differ in terms of baseline characteristics. The median overall survival (OS) was 26.8 months (95%CI 21.6-44.2) in sRCC and 35.3 months (95%CI 30.2-40.4) in non-sRCC patients (p = .013). The median progression-free survival (PFS) was longer in non-sRCC patients compared to sRCC (14.5 vs. 12.3 months, p = .064). In patients treated with first-line IO + TKI the median OS was 34.4 months compared to 26.4 months of those who received IO + IO (p = .729). The median PFS was 12.4 months with IO + TKI and 12.3 months with IO + IO (p = .606). In conclusion, we confirm that sRCC are aggressive tumors with poor prognosis. IO-based combinations improve survival outcomes of sRCC patients, regardless from the type of strategy (IO + IO versus IO + TKI) adopted.

Effect of sex-specific abdominal fat tissue composition on WHO/ISUP nuclear grade of clear cell renal cell carcinoma.

Background/aim: To investigate the relationship between sex-related visceral obesity and WHO/ISUP nuclear grade in clear cell renal cell carcinoma (ccRCC). Materials and methods: Between January 2018 and June 2022, 95 patients (56 men and 39 women) with pathologically proven ccRCC who underwent abdominal computed tomography examination were retrospectively examined. The patients were classified into two groups: low- and high-WHO/ISUP nuclear grade ccRCC (n = 58 and n = 37), respectively. Patient height, weight, body mass index (BMI), sex, age, subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), and percentage of visceral fat (VF%) were recorded for the two groups. Results: No significant differences were found in age, BMI, SFA, or TFA, but VFA and VF% were significantly higher in the high-grade patient group. In males, maximal tumor diameter (MTD) (67.8% sensitivity and 76.9% specificity) had the highest area under the curve (AUC), while in females, VF% (70.0% sensitivity and 73.7% specificity) had the highest AUC. VF% revealed an odds ratio (OR) of 1.09 in females with high-grade ccRCC, and in males, MTD was an independent predictor of ccRCC with an OR of 1.03. Conclusions: Sex-related body fat tissue, including VFA and VF%, could be used for estimating WHO/ISUP nuclear grade in patients with ccRCC, especially in females.

Renal cell carcinoma as a cause of aortic tumor thrombus embolization and acute limb ischemia.

This article presents a unique case of acute limb ischemia resulting from arterial tumor embolism secondary to renal cell carcinoma involving an aortobi-iliac bypass graft. To the best of our knowledge, this instance is the first documented in the literature of such a complication. The patient, a man in his 70s with a complex medical history, underwent bilateral femoral embolectomy and subsequent endovascular intervention for the resolution of the tumor thrombus. The rarity of this phenomenon poses challenges in formulating a standardized management strategy.

Rare type of Bellini Duct Carcinoma in a Patient With Cacchi-Ricci Disease: A Case Report and Mini-Review.

Medullary sponge kidney (MSK) is an uncommon kidney malformation, characterized by cystic dilatation of the precalyceal papillary collecting ducts. Urography and computed tomography scan represent the gold standard to detect this congenital disorder. A clear diagnosis is not always feasible, especially in the presence of a concomitant renal mass, which in turn can be difficult to detect in MSK patients. When conventional imaging is inconclusive, a renal biopsy can be considered in doubtful cases. Here, we report a unique case of a Bellini duct carcinoma in a patient with MSK and we review the literature on this complex condition.

Prognostic significance of immune evasion-related genes in clear cell renal cell carcinoma immunotherapy.

Clear cell renal cell carcinoma (ccRCC) represents a prevalent malignancy of the urinary system. Despite the integration of immune checkpoint inhibitors (ICIs) into the treatment paradigm for advanced RCC, resistance to immunotherapy has emerged as a pivotal determinant impacting the clinical outlook of ccRCC. Accumulating evidence underscores the pivotal role of immune evasion-related genes and pathways in enabling tumor escape from host immune surveillance, consequently influencing patients' responsiveness to immunotherapy. Nonetheless, the clinical relevance of immune evasion-related genes in ccRCC patients undergoing immunotherapy remains inadequately understood. In this study, we aggregated RNA sequencing and clinical data from ccRCC patients across three cohorts: the Cancer Genome Atlas (TCGA), CheckMate cohorts, and the JAVELIN Renal 101 trial. Leveraging a curated immune evasion-related gene set from Lawson et al., we employed the LASSO algorithm and Cox regression analysis to identify eight genes (LPAR6, RGS5, NFYC, PCDH17, CENPW, CNOT8, FOXO3, SNRPB) significantly associated with immune therapy prognosis (HR, 3.57; 95 % CI, 2.38-5.35; P<0.001). A predictive algorithm developed utilizing these genes exhibited notable accuracy in forecasting patients' progression-free survival in the training set (AUC, 0.835). Furthermore, stratification of patients by risk score revealed discernible differences in immunotherapy response and tumor microenvironment. In summary, we present a prognostic model intricately linked with immune status and treatment response. For ccRCC patients undergoing immunotherapy, this approach holds promise in aiding clinical decision-making by providing more precise and tailored treatment recommendations.

Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

BACKGROUND: The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and healthcare efficiencies. PATIENTS AND METHODS: CheckMate 67T (NCT04810078) was a phase 3, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20,000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). Primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis (time-averaged serum concentration over the first 28 days [Cavgd28], and minimum steady-state serum concentration [Cminss]; noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios [GMR] ≥0.8). Objective response rate (ORR) was a key secondary endpoint powered for noninferiority (noninferiority threshold: lower boundary of 95% CI of relative risk of ORR [subcutaneous versus intravenous nivolumab] ≥0.60). RESULTS: Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI, 2.001-2.200) and 1.774 (90% CI, 1.633-1.927), respectively. After 8 months minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI, 19.0-30.0) versus 18.2% with intravenous nivolumab (95% CI, 13.6-23.6; relative risk: 1.33 [95% CI, 0.94-1.87]). Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. CONCLUSION: Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

Upfront Versus Deferred Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND AND OBJECTIVE: Despite its well-established role in metastatic renal cell carcinoma (mRCC), the optimal timing of cytoreductive nephrectomy (CN) is unclear. The aim of this systematic review is to compare the overall survival (OS) between upfront (uCN) and deferred (dCN) CN. METHODS: The MEDLINE, EMBASE, and Web of Science databases were queried (end of search date: August 26, 2023) for studies comparing OS between uCN and dCN in mRCC patients. We reconstructed individual patient data from published Kaplan-Meier survival curves and performed one- and two-stage meta-analyses, using 6- and 12-mo landmarks to mitigate immortal time bias. We also performed subgroup analyses according to systemic therapy (ST) type and Memorial Sloan Kettering Cancer Center (MSKCC)/International Metastatic RCC Database Consortium (IMDC) risk scores. We assessed the risk of bias using the Risk of Bias in Non-randomized Studies of Interventions and Risk of Bias 2.0 tools. KEY FINDINGS AND LIMITATIONS: We identified 12 (two randomized trials and ten retrospective cohorts) eligible studies with a total of 3323 (2610 uCN and 713 dCN) patients. There were no statistically significant differences in the baseline characteristics of the two groups, other than the number of metastases and ST type. The overall risk of bias was high in nine out of 12 studies. Deferred CN was associated with superior OS in the primary analysis (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65-0.84; 5-yr life expectancy difference 5.15 mo, 95% CI 3.23-7.08), all secondary analyses, as well as the tyrosine kinase inhibitor-treated (HR 0.61, 95% CI 0.51-0.74), immune checkpoint inhibitor-treated (HR 0.67, 95% CI 0.46-0.97), and intermediate IMDC/MSKCC risk (HR 0.73, 95% CI 0.55-0.97) subgroups. CONCLUSIONS AND CLINICAL IMPLICATIONS: Deferred CN is associated with superior OS compared with uCN in mRCC patients treated with contemporary STs. Randomized studies are warranted to confirm these findings. Predictive models are needed to optimize the selection of patients most likely to benefit from dCN. PATIENT SUMMARY: In this report, we compared the outcomes of nephrectomy performed before (upfront) or after (deferred) starting systemic therapy for patients with metastatic kidney cancer. We found that deferred nephrectomy is associated with superior survival compared with upfront nephrectomy, irrespective of the systemic therapy regimens used.

Sunitinib in Patients with Metastatic Renal Cell Carcinoma with Favorable Risk: Be Aware of PD-L1 Expression.

The treatment landscape for metastatic renal cell carcinoma (RCC) has advanced significantly with first-line immunotargeted therapy combinations. However, no statistically significant differences were observed in the cohort of patients with favorable risk and some oncologists continue to use sunitinib in these patients. PD-L1 expression has emerged as a negative prognostic factor in RCC, particularly in sunitinib-treated patients, where higher PD-L1 levels are linked to worse outcomes. This article discusses the potential risks associated with the use of sunitinib in PD-L1-positive patients.

AGBL2 promotes renal cell carcinoma cells proliferation and migration via α-tubulin detyrosination.

Background: AGBL2's role in tumorigenesis and cancer progression has been reported in several cancer studies, and it is closely associated with α-tubulin detyrosination. The roles of AGBL2 and α-tubulin detyrosination in renal cell carcinoma (RCC) pathogenesis remain unclear and require further investigation. Methods: In this study, we conducted an analysis of AGBL2 expression differences between renal clear cell carcinoma tissues and normal tissues using data from The Cancer Genome Atlas (TCGA). We performed a comprehensive prognostic analysis of AGBL2 in Kidney Renal Clear Cell Carcinoma (KIRC) using univariate and multivariate Cox regression. Based on the results of the Cox analysis, we constructed a prognostic model to assess its predictive capabilities. Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of AGBL2 in renal cancer. We conducted further validation by analyzing cancer tissue samples and renal cancer cell lines, which confirmed the role of AGBL2 in promoting RCC cell proliferation and migration through in vitro experiments. Additionally, we verified the impact of AGBL2's detyrosination on α-tubulin using the tubulin carboxypeptidase (TCP) inhibitor parthenolide. Finally, we performed sequencing analysis on AGBL2 knockdown 786-O cells to investigate the correlation between AGBL2, immune infiltration, and AKT phosphorylation. Moreover, we experimentally demonstrated the enhancing effect of AGBL2 on AKT phosphorylation. Results: TCGA analysis revealed a significant increase in AGBL2 expression in RCC patients, which was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). According to the analysis results, we constructed column-line plots to predict the 1-, 3-, and 5-year survival outcomes in RCC patients. Additionally, the calibration plots assessing the model's performance exhibited favorable agreement with the predicted outcomes. And the ROC curves showed that AGBL2 showed good diagnostic performance in KIRC (AUC = 0.836)). Cell phenotyping assays revealed that AGBL2 knockdown in RCC cells significantly inhibited cell proliferation and migration. Conversely, overexpression of AGBL2 resulted in increased cell proliferation and migration in RCC cells. We observed that AGBL2 is predominantly located in the nucleus and can elevate the detyrosination level of α-tubulin in RCC cells. Moreover, the enhancement of RCC cell proliferation and migration by AGBL2 was partially inhibited after treatment with the TCP inhibitor parthenolide. Analysis of the sequencing data revealed that AGBL2 is associated with a diverse array of biological processes, encompassing signal transduction and immune infiltration. Interestingly, AGBL2 expression exhibited a negative correlation with the majority of immune cell infiltrations. Additionally, AGBL2 was found to enhance the phosphorylation of AKT in RCC cells. Conclusion: Our study suggests that AGBL2 fosters RCC cell proliferation and migration by enhancing α-tubulin detyrosination. Moreover, elevated AGBL2 expression increases phosphorylation of AKT in RCC cells.

Prognostic models for predicting oncological outcomes after surgical resection of a nonmetastatic renal cancer: A critical review of current literature.

Prognostic models can be valuable for clinicians in counseling and monitoring patients after the surgical resection of nonmetastatic renal cell carcinoma (nmRCC). Over the years, several risk prediction models have been developed, evolving significantly in their ability to predict recurrence and overall survival following surgery. This review comprehensively evaluates and critically appraises current prognostic models for nm-RCC after nephrectomy. The last 2 decades have witnessed a notable increase in the development of various prognostic risk models for RCC, incorporating clinical, pathological, genomic, and molecular factors, primarily using retrospective data. Only a limited number of these models have been developed using prospective data, and their performance has been less effective than expected when applied to broader, real-life patient populations. Recently, artificial intelligence (AI), especially machine learning and deep learning algorithms, has emerged as a significant tool in creating survival prediction models. However, their widespread application remains constrained due to limited external validation, a lack of cost-effectiveness analysis, and unconfirmed clinical utility. Although numerous models that integrate clinical, pathological, and molecular data have been proposed for nm-RCC risk stratification, none have conclusively demonstrated practical effectiveness. As a result, current guidelines do not endorse a specific model. The ongoing development and validation of AI algorithms in RCC risk prediction are crucial areas for future research.

VHL synthetic lethality screens uncover CBF-ß as a negative regulator of STING.

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor ß (CBF-ß) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-ß. Mechanistically, CBF-ß loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-ß at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-ß in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

Solitary Masseter Metastasis from Renal Cell Carcinoma: A Rare Case Report.

Background: Renal cell carcinoma (RCC) frequently presents with metastatic spread, sometimes many years after treatment. However, masseter muscle metastasis is extremely rare, with just six reported cases in literature, and none in the United Kingdom (UK). Given its rarity, we hope our case will add to the body of knowledge on the subject and encourage clinicians to maintain a high index of suspicion when reviewing patients with previous RCC and an unexplained mass. Case Summary: Here presented is a 62-year-old man who previously underwent left radical nephrectomy in 2014 for an 11 cm clear cell renal carcinoma (ccRCC). He had subsequent right adrenalectomy in 2020 for a 19 mm recurrence, which was excised with clear margins. He then presented in 2022 with a three-month history of enlarging painless mass in the left side of his face. Imaging was inconclusive, but biopsy showed a singular ccRCC metastatic deposit in the masseter. Surgical resection was not possible due to extension into the infratemporal fossa, and he was referred for radiotherapy. Conclusions: Masseter muscle, whilst rare, can be a site of distant metastases for renal cell carcinoma. Diagnosis relies on a high index of clinical suspicion in patients with prior RCC, combined with cross-sectional imaging and biopsy. Early detection gives the best chance for cure with metastasectomy.

NOP2-mediated 5-methylcytosine modification of APOL1 messenger RNA activates PI3K-Akt and facilitates clear cell renal cell carcinoma progression.

Background: By regulating the functions of multiple RNAs, 5-methylcytosine (m5C) RNA methylation, particularly mediated by NOP2, is involved in tumorigenesis and developments. However, the specific functions and potential mechanisms of m5C, especially involving NOP2, in clear-cell renal cell carcinoma (ccRCC), remain unclear. Methods: NOP2 expression in cell lines and patient tissues was detected using western blotting, quantitative real-time polymerase chain reaction (RT-qPCR), and immunohistochemistry. The biological effects of NOP2 on ccRCC cells were investigated through a series of in vitro and in vivo experiments. To explore the potential regulatory mechanisms by which NOP2 affects ccRCC progression, m5C bisulfite sequencing, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation (RIP/MeRIP) RT-qPCR assay, luciferase reporter assay, RNA stability assay, and bioinformatic analysis were performed. Results: NOP2 expression was significantly upregulated in ccRCC tissues and was associated with poor prognosis. Moreover, loss-of-function and gain-of-function assays demonstrated that NOP2 altered ccRCC cell proliferation, migration, and invasion. Mechanistically, NOP2 stimulated m5C modification of apolipoprotein L1 (APOL1) mRNA, and m5C reader YBX1 stabilized APOL1 mRNA through recognizing and binding to m5C site in the 3'-untranslated regions. Silencing APOL1 expression inhibited ccRCC cell proliferation in vitro and tumor formation in vivo. Furthermore, NOP2/APOL1 affected ccRCC progression via the PI3K-Akt signaling pathway. Conclusion: NOP2 functions as an oncogene in ccRCC by promoting tumor progression through the m5C-dependent stabilization of APOL1, which in turn regulates the PI3K-Akt signaling pathway, suggesting a potential therapeutic target for ccRCC.

TREM2 promotes the proliferation and invasion of renal cell carcinoma cells by inhibiting the P53 signaling pathway.

Renal cell carcinoma (RCC) is a prevalent malignancy characterized by poor prognosis and high mortality. The role of triggering receptor expressed on myeloid cells-2 (TREM2) in RCC progression has been increasingly recognized, yet its underlying mechanisms remain to be fully elucidated. The aim of the present study was to assess the effects of TREM2 on RCC cells and its potential mechanisms. Lentiviral transfection was used to knockdown and overexpress TREM2 in RCC cells, and the expression level of TREM2 was evaluated using reverse transcription-quantitative PCR. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess the proliferation of the RCC cells. Cell migration and invasion was evaluated using the wound healing assay and Transwell assay, respectively. Western blotting was used to assess the expression levels of TREM2, P53, p-P53, P21 and p-P21 in TREM2 knockdown or overexpression RCC cells. The results demonstrated that the expression level of TREM2 was significantly higher in cancer tissues compared with adjacent normal tissues. The results of the CCK-8 and EdU assays demonstrated that knockdown of TREM2 significantly inhibited the proliferation of RCC cells, whilst overexpression of TREM2 enhanced the proliferation of RCC cells. The results of the wound healing and Transwell assay revealed that, compared with the control group, the overexpression of TREM2 significantly increased the migration and invasion of RCC cells, whereas knockdown of TREM2 significantly decreased the migration of RCC cells. In addition, western blotting demonstrated that the phosphorylation levels of P53 and P21 proteins were significantly increased after TREM2 knockdown in RCC cells. In conclusion, TREM2 is highly expressed in RCC tissues and promotes the migration of RCC cells by inhibiting the P53 signaling pathway. The present study provides new insights into the regulatory effect of TREM2 on RCC and further reveals the potential of TREM2 as a therapeutic target for RCC.

CT-Guided Online Adaptive Radiotherapy Delivered via Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) for a Bulky Thoracic and Abdominal Mass in Oligometastatic Renal Cell Carcinoma.

In the context of oligometastatic renal cell carcinoma (RCC), local treatment with stereotactic body radiotherapy (SBRT) may improve oncologic outcomes. However, the location and size can often pose a technical challenge in standard SBRT delivery, and the dose is potentially limited by nearby organs at risk (OARs). Online adaptive radiotherapy (oART) improves radiation delivery by personalizing high-dose fractions to account for daily stochastic variations in patient anatomy or setup. The oART process aims to maximize tumor control and enhances precision by tailoring to a more accurate representation of a patient in near-real time. The proceeding re-optimization can mitigate the uncertainty inherent in the traditional radiation delivery workflow and precludes the need for larger margins that account for anatomical variations and setup errors. Here, we describe a case of oligometastatic RCC with a bulky (>300 cm3) pleural-based left lower lobe mass extending into the upper abdomen treated via personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR). Three fractions were delivered four weeks apart allowing for tumor shrinkage of these bulky lesions, and oART permitted on-table adaptation of the plan without traditional re-simulation and re-planning required during off-line adaptive radiotherapy. The plan was designed for the Ethos linear accelerator (Varian Medical Systems, Inc., Palo Alto, CA, USA). The prescription dose was 36 Gray (Gy) in three fractions, and the adapted plan was selected in each treatment over the scheduled plan due to better target coverage and reversal of OAR dose violations. The adapted plan met all OAR dose constraints, and it achieved higher target coverage in the first two PULSAR fractions compared to the scheduled plan. In the third fraction, the cumulative point dose was approaching the maximum heart tolerance, and target coverage was accordingly compromised based on clinical judgment. There was evidence of tumor regression throughout the course of treatment, and the patient did not develop any significant radiation-related toxicities. Follow-up imaging has demonstrated the overall stable size of her lesion without any evidence of disease progression. Our case reflects the benefit of adaptive SBRT delivery to a bulky mass near multiple OARs in the setting of oligometastatic RCC. The adapted plan allowed for prioritization of critical structures on a fraction-by-fraction basis while preserving the therapeutic intent of SBRT. Further integration of advanced imaging techniques, optimal disease-specific systemic immunotherapies or targeted therapies, and refinement of patient selection will be crucial in identifying which patients would most benefit from an adaptive approach.

A Rare Case of Collecting Duct Carcinoma: A Comprehensive Analysis Using Ultrasound, Computed Tomography, and Histopathological Examination.

Collecting duct renal cell carcinoma (cdRCC) is an exceptionally rare and aggressive subtype of renal cell carcinoma, accounting for approximately 1% of all renal tumors. This case is notable due to the comprehensive use of multi-modality imaging and detailed histopathological examination, offering valuable insights into the diagnostic challenges and management of this rare condition. A 64-year-old male presented with progressive right flank pain, hematuria, and decreased urine output. Imaging studies revealed a hypoechoic lesion in the right kidney, predominantly located in the hilar and perihilar regions, suggestive of a malignant renal tumor. Further diagnostic evaluation, including a right radical nephrectomy, was performed. The histopathological examination of the resected tissue confirmed the diagnosis of cdRCC, characterized by a tubulopapillary growth pattern, significant pleomorphism, and sarcomatoid changes. Immunohistochemical analysis showed strong positivity for epithelial membrane antigen and CK7, confirming the aggressive nature of the tumor. This case underscores the importance of early diagnosis and a comprehensive diagnostic approach to managing cdRCC. Despite advances in imaging techniques, a definitive diagnosis often relies on histopathological and immunohistochemical analysis. The aggressive nature of cdRCC and its generally poor prognosis highlight the need for prompt and accurate diagnosis to potentially improve patient outcomes. This report adds to the limited literature on cdRCC, emphasizing the challenges and considerations in diagnosing and managing this rare form of renal carcinoma.