Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic ...alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.
An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this ...study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.
Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies ...suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.
Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological ...behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal ...role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC ...and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase(SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.
Urachal carcinoma is a rare cancer. Correct staging is mandatory, and surgical intervention is the treatment in localized cases. Advanced disease requires chemotherapy, even if oncological outcomes ...remain poor.
Urachal carcinoma is a rare urological disease. The shortage of data about diagnosis and surgical treatment in literature makes it hard for clinicians to make a decision. Indeed, urachal carcinoma is an aggressive disease that requires prompt staging and treatment to ensure the best outcome for patients. We reviewed the last evidence about the management of urachal carcinoma to provide an easy-to-use guide for clinical practice.
Urachal carcinoma is a rare malignancy. The literature on this challenging disease remains limited. Herein, we provide a practical guide for its management from diagnosis to treatment, which in most cases requires surgical intervention or chemotherapy.
Several models were found to be plausible for estimation of percentage estimated glomerular filtration rate (eGFR) loss at 1 yr after minimally invasive partial nephrectomy. The best model for ...predicting long-term eGFR loss included postoperative eGFR percentage loss, sex, ischemia technique, and preoperative eGFR as variables.
Long-term renal function after partial nephrectomy (PN) is difficult to predict as it is influenced by several modifiable and nonmodifiable variables, often intertwined in complex relations.
To identify variables influencing long-term renal function after PN and to assess their relative weight.
A total of 457 patients who underwent either robotic (n = 412) or laparoscopic PN (n = 45) were identified from a multicenter international database.
The 1-yr estimated glomerular filtration rate (eGFR) percentage loss (1YPL), defined as the eGFR percentage change from baseline at 1 yr after surgery, was the outcome endpoint. Predictors evaluated included demographic data, tumor features, and operative and postoperative variables. Bayesian multimodel analysis of covariance was used to build all possible models and compare the fit of each model to the data via model Bayes factors. Bayesian model averaging was used to quantify the support for each predictor via the inclusion Bayes factor (BFincl). High-dimensional undirected graph estimation was used for network analysis of conditional independence between predictors.
Several models were found to be plausible for estimation of 1YPL. The best model, comprising postoperative eGFR percentage loss (PPL), sex, ischemia technique, and preoperative eGFR, was 207 times more likely than all the other models regarding relative predictive performance. Its components were part of the top 44 models and were the predictors with the highest BFincl. The role of cold ischemia, solitary kidney status, surgeon experience, and type of renorraphy was not assessed.
Preoperative eGFR, sex, ischemia technique, and PPL are the best predictors of eGFR percentage loss at 1 yr after minimally invasive PN. Other predictors seem to be irrelevant, as their influence is insignificant or already nested in the effect of these four parameters.
Kidney function at 1 year after partial removal of a kidney depends on sex, the technique used to halt blood flow to the kidney during surgery, and kidney function at baseline and in the early postoperative period.
Current evidence suggests that retroperitoneal robot-assisted partial nephrectomy (RAPN) offers similar surgical outcomes to transperitoneal RAPN, and potential advantages in terms of shorter ...operative time and length of stay. Despite the presence of a high number of high-quality comparative studies, no randomized clinical trials are available.
Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity as primary minimally invasive surgical treatment for localized renal tumors, and it has preferably been performed with a transperitoneal approach. However, the retroperitoneal approach represents an alternative approach given potential advantages.
To provide an updated analysis of the comparative outcomes of retroperitoneal RAPN (R-RAPN) versus transperitoneal RAPN (T-RAPN).
A systematic review of the literature was performed up to September 2021 using MEDLINE, EMBASE, and Web of Science databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. A sensitivity analysis was performed considering only matched-pair studies.
Seventeen studies, which were published between 2013 and 2021, were retrieved. None of them was a randomized clinical trial. Among the 6,266 patients included in the meta-analysis, 2261 (36.1%) and 4,005 (63.9%) underwent R-RAPN and T-RAPN, respectively. No significant difference was found in terms of baseline features. The T-RAPN group presented a higher rate of male patients (odds ratio OR: 0.86, p = 0.03) and larger tumor size (weighted mean difference WMD: 0.2 cm; p = 0.003). The R-RAPN group reported more frequent posterior renal masses (OR: 0.23; p < 0.0001). The retroperitoneal approach presented lower estimated blood loss (WMD: 30.41 ml; p = 0.001), shorter operative time (OT; WMD: 20.36 min; p = 0.0001), and shorter length of stay (LOS; WMD: 0.35 d; p = 0.002). Overall complication rates were 13.7% and 16.05% in the R-RAPN and T-RAPN groups, respectively (OR: 1.32; p = 0.008). There were no statistically significant differences between the two groups regarding major (Clavien-Dindo classification ≥3 grade) complication rate, “pentafecta” achievement, as well as positive margin rates. When considering only matched-pair studies, no difference between groups was found in terms of baseline characteristics. Posterior renal masses were more frequent in the R-RAPN group (OR: 0.6; p = 0.03). Similar to the analysis of the entire cohort, R-RAPN reported lower EBL (WMD: 35.56 ml; p < 0.0001) and a shorter OT (WMD: 18.31 min; p = 0.03). Overall and major complication rates were similar between the two groups. The LOS was significantly lower for R-RAPN (WMD: 0.46 d; p = 0.02). No statistically significant difference was found between groups in terms of overall PSM rates.
R-RAPN offers similar surgical outcomes to T-RAPN, and it carries potential advantages in terms of shorter OT and LOS. Available evidence remains limited by the lack of randomized clinical trials.
In this review of the literature, we looked at comparative outcomes of two surgical approaches to robot-assisted partial nephrectomy. We found that the retroperitoneal technique offers similar surgical outcomes to the transperitoneal one, with potential advantages in terms of shorter operative time and length of hospital stay.
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