TPD52L2 as a potential prognostic and immunotherapy biomarker in clear cell renal cell carcinoma.

Background: Tumor Protein D52-Like 2 (TPD52L2) is a tumor-associated protein that participates in B-cell differentiation. However, the role of TPD52L2 in the pathological process of clear cell renal cell carcinoma (ccRCC) is unclear. Methods: Multiple omics data of ccRCC samples were obtained from public databases, and 5 pairs of ccRCC tissue samples were collected from the operating room. Wilcox, chi-square test, Kaplan-Meier method, receiver operating characteristic curve, regression analysis, meta-analysis, and correlation analysis were used to clarify the relationship of TPD52L2 with clinical features, prognosis, and immune microenvironment. Functional enrichment analysis was performed to reveal the potential pathways in which TPD52L2 participates in the progression of ccRCC. The siRNA technique was used to knockdown in the expression level of TPD52L2 in 786-O cells to verify its effect on ccRCC progression. Results: First, TPD52L2 was found to be upregulated in ccRCC at both mRNA and protein levels. Second, TPD52L2 was significantly associated with poor prognosis and served as an independent prognostic factor. Moreover, TPD52L2 expression was regulated by DNA methylation, and some methylation sites were associated with ccRCC prognosis. Third, TPD52L2 overexpression may participate in the pathological process through various signaling pathways such as cytokine-cytokine receptor interactions, PI3K-Akt, IL-17, Wnt, Hippo signaling pathway, and ECM-receptor interactions. Interestingly, TPD52L2 expression level was also closely related to the abundance of various immune cells, immune checkpoint expression, and TMB. Finally, in vitro experiments confirmed that knocking down TPD52L2 can inhibit the proliferation, migration, and invasion abilities of ccRCC cells. Conclusion: This study for the first time revealed the upregulation of TPD52L2 expression in ccRCC, which is closely associated with poor prognosis of patients and is a potentially valuable therapeutic and efficacy assessment target for immunotherapy.

The mitochondrial fusion-associated protein MFN2 can be used as a novel prognostic molecule for clear cell renal cell carcinoma.

BACKGROUND: Mitofusin 2 (MFN2) plays an important role in many tumors, but how its role in renal clear cell carcinoma needs further research. METHODS: In this study, we analyzed the expression of MFN2 in renal clear cell carcinoma tissues and normal kidney tissues through the Cancer Genome Atlas (TCGA) database and our clinical samples.Enrichment analysis was performed to determine MFN2-related pathways and biological functions. The correlation of MFN2 expression with immune cells was analyzed.The correlation of the expression of methylation and the methylation sites of MFN2 were analyzed by UALCAN and TCGA databases. Univariate / multivariate COX risk regression and Kaplan-Meier methods were used to determine the prognostic value of MFN2.Nomograms were drawn to predict overall survival (OS) at 1,3, and 5 years. We investigated the role of MFN2 in renal cancer cells using CCK 8, clone formation, wound healing assay, and methylase qPCR experiments. RESULTS: MFN2 is poorly expressed in renal clear cell carcinoma compared to normal kidney tissue,and is significantly negatively associated with TNM stage, histological grade and pathological stage.MFN2 was directly associated with OS after multivariate Cox regression analysis.MFN2 shows a hypomethylation state and shows a positive correlation with multiple methylation sites.Signaling pathways through functional enrichment to B-cell receptors and oxidative stress-induced senescence.Moreover, the low expression of MFN2 was positively correlated with the degree of immune cell infiltration in a variety of immune cells.In vitro experiments showed that overexpression of MFN2 significantly inhibited the proliferation and migration of renal clear cells and promoted methylation. CONCLUSIONS: In conclusion, MFN2 can be used as a novel prognostic marker for renal clear cell carcinoma and requires further investigation of its role in tumor development.

Prediction of oxygen distribution in the waste mass from an aeration well in bioreactor landfills.

The key to upgrade the efficiency of aerobic remediation of landfills is to determine the distribution characteristics of oxygen concentration during aerobic ventilation. This study discusses the distribution law of oxygen concentration with time and radial distance based on a single-well aeration test at an old landfill site. The transient analytical solution of the radial oxygen concentration distribution was deduced using the gas continuity equation and approximation of calculus and logarithmic functions. Oxygen concentration data from the field monitoring were compared with the results predicted by the analytical solution. The results indicated that the oxygen concentration initially increased and then decreased with prolonged aeration time. With an increase in radial distance, the oxygen concentration rapidly declined, followed by a gradual decrease. The influence radius of the aeration well increased slightly when the aeration pressure increased from 2 to 20 kPa. The field test data agreed with the analytical solution prediction results, preliminarily verifying the reliability of the oxygen concentration prediction model. Results from this study provide a basis of guidelines for the design, operation and maintenance management of a landfill aerobic restoration project.

Comprehensive analysis of fatty acid metabolism-related gene signatures for predicting prognosis in patients with prostate cancer.

Fatty acid metabolism (FAM) is an important factor in tumorigenesis and development. However, whether fatty acid metabolism (FAM)-related genes are associated with prostate cancer (PCa) prognosis is not known. Therefore, we established a novel prognostic model based on FAM-related genes to predict biochemical recurrence in PCa patients. First, PCa sequencing data were acquired from TCGA as the training cohort and GSE21032 as the validation cohort. Second, a prostate cancer prognostic model containing 10 FAM-related genes was constructed using univariate Cox and LASSO. Principal component analysis and t-distributed stochastic neighbour embedding analysis showed that the model was highly effective. Third, PCa patients were divided into high- and low-risk groups according to the model risk score. Survival analysis, ROC curve analysis, and independent prognostic analysis showed that the high-risk group had short recurrence-free survival (RFS), and the risk score was an independent diagnostic factor with diagnostic value in PCa patients. External validation using GSE21032 also showed that the prognostic model had high reliability. A nomogram based on a prognostic model was constructed for clinical use. Fourth, tumor immune correlation analyses, such as the ESTIMATE, CIBERSORT algorithm, and ssGSEA, showed that the high-risk group had higher immune cell infiltration, lower tumour purity, and worse RFS. Various immune checkpoints were expressed at higher levels in high-risk patients. In summary, this prognostic model is a promising prognostic biomarker for PCa that should improve the prognosis of PCa patients. These data provide new ideas for antitumour immunotherapy and have good potential value for the development of targeted drugs.

The pleiotropic mode and molecular mechanism of macrophages in promoting tumor progression and metastasis

Macrophages are the most abundant immune cells in primary and metastatic tumor tissues. Studies have shown that macrophages mainly exhibit a tumor-promoting phenotype and play a key role in tumor progression and metastasis. Therefore, many macrophage-targeted drugs have entered clinical trials. However, compared to preclinical studies, some clinical trial results showed that macrophage-targeted therapy did not achieve the desired effect. This may be because most of what we know about macrophages comes from in vitro experiments and animal models, while macrophages in the more complex human microenvironment are still poorly understood. With the development of technologies such as single-cell RNA sequencing, we have gained a new understanding of the origin, classification and functional mechanism of tumor-associated macrophages. Therefore, this study reviewed the recent progress of macrophages in promoting tumor progression and metastasis, aiming to provide some help for the formulation of optimal strategies for macrophage-targeted therapy (AU)

TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway.

The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. This study explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.

The pleiotropic mode and molecular mechanism of macrophages in promoting tumor progression and metastasis.

Macrophages are the most abundant immune cells in primary and metastatic tumor tissues. Studies have shown that macrophages mainly exhibit a tumor-promoting phenotype and play a key role in tumor progression and metastasis. Therefore, many macrophage-targeted drugs have entered clinical trials. However, compared to preclinical studies, some clinical trial results showed that macrophage-targeted therapy did not achieve the desired effect. This may be because most of what we know about macrophages comes from in vitro experiments and animal models, while macrophages in the more complex human microenvironment are still poorly understood. With the development of technologies such as single-cell RNA sequencing, we have gained a new understanding of the origin, classification and functional mechanism of tumor-associated macrophages. Therefore, this study reviewed the recent progress of macrophages in promoting tumor progression and metastasis, aiming to provide some help for the formulation of optimal strategies for macrophage-targeted therapy.

Combined single-cell RNA-seq and bulk RNA-seq to analyze the expression and role of TREM2 in bladder cancer.

Currently, reprogramming macrophages has emerged as one of the most promising therapeutic strategies in cancer treatment. Many studies have found that myeloid trigger receptor-2 (TREM2) is mainly expressed on tumor-associated macrophages (TAMs), and targeting TREM2 promotes reprogramming of TAMs and enhances the immunotherapeutic effect of tumors. Nevertheless, the expression and role of TREM2 in different tumor tissues are still controversial. For example, some studies have found that TREM2 can also be expressed on tumor cells and exert pro-tumor functions. It has also been found that TREM2 expression can inhibit tumorigenesis and progression. In fact, there are still no relevant studies on the expression and role of TREM2 in bladder cancer (BLCA). Therefore, the present study combined single-cell RNA-seq and bulk RNA-seq to analyze the expression, role, and molecular mechanism of TREM2 in BLCA. We found that TREM2 was predominantly expressed on TAMs in BLCA, followed by tumor epithelial cells. This finding could be useful for further exploration of the role and mechanism of TREM2. Moreover, TREM2 expression correlates with clinical progression and immunotherapy efficacy, and is an important predictor of prognosis for BLCA patients. Not only that, we also found that TREM2 may exert its effects by promoting epithelial mesenchymal transition (EMT) and T-cell exhaustion. TREM2+ TAMs may play an important pro-tumor role through PTN, ANGPTL, and VISFATIN pathways. In conclusion, our study found that TREM2 is not only a predictor of BLCA prognosis, but also a potential therapeutic target for BLCA.

The prognostic significance of controlling nutritional status (CONUT) score for surgically treated renal cell cancer and upper urinary tract urothelial cancer: a systematic review and meta-analysis.

In order to evaluate the predictive effect of the controlled nutritional status (CONUT) score on the prognosis of patients with renal cell carcinoma (RCC) and upper urinary tract urothelial carcinoma (UTUC), a meta-analysis was performed. This systematic review has been registered on PROSPERO, the registration ID is CRD42021251879. A systematic search of the published literature using PubMed, Web of Science, Cochrane Library, EMBASE, and MEDLINE was performed. The fields of "renal cell cancer," "upper tract urothelial cancer," and "controlling nutritional status" and other fields were used as search terms. STATA 16 software was used to carry out data merging and statistical analysis of binary variables, Q test and χ2 tests were used to verify the heterogeneity between the included works of studies. Subgroup analysis and sensitivity analysis were used to explain the sources of heterogeneity between studies. Begg's test was used to assess publication bias between studies. From the first 542 studies retrieved, through strict inclusion and exclusion criteria, 7 studies finally met the requirements and were included in the meta-analysis. Pooled results indicated that high CONUT indicates worse over survival (OS) [HR = 1.70, 95% CI (1.43-2.03), P = 0.02], cancer-specific survival (CSS) [HR = 1.84, 95% CI (1.52-2.23), P = 0.01], recurrence-free survival (RFS) [HR = 1.60, 95% CI (1.26-2.03), P = 0.116], and disease-free survival (DFS) [HR = 1.47, 95% CI (1.20-1.81), P = 0.03]. Based on cancer type, cutoff value, region, and sample size, a subgroup analysis was performed. The results showed that OS and CSS were not affected by the above factors, and the high CONUT score before surgery predicted worse OS and CSS. In conclusion, this meta-analysis revealed that the preoperative CONUT score is a potential independent predictor of the postoperative prognosis of RCC/UTUC patients. A high CONUT predicts worse OS/CSS/DFS and RFS in patients.

The Microultrasound-Guided Prostate Biopsy in Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

Background: To compare the detection rate of microultrasound with that of multiparametric magnetic resonance imaging targeted biopsy (mpMRI-TB) for prostate cancer (PCa) diagnosis. Methods: The studies on microultrasound prostate biopsy for PCa diagnosis were searched in PubMed, Cochrane library, and EMBASE databases from inception to April 2021. We performed a systematic review and cumulative meta-analysis based on search results using Software Rev-Man 5.3. Results: A total of 11 studies involving 1081 patients were included. The meta-analysis showed that no significant difference was found between microultrasound and mpMRI-TB in the total detection of PCa (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 0.85-1.21, p = 0.89), of grading groups (GGs) = 1 (OR: 0.92, 95% CI: 0.68-1.25, p = 0.59), of GGs ≥2 (OR:1.01, 95% CI: 0.83-1.22, p = 0.92), and of GGs ≥3 (OR: 1.31, 95% CI: 0.95-1.81, p = 0.10). Conclusions: Microultrasound-guided prostate biopsy provides detection rates for PCa diagnosis comparable with those of the mpMRI-TB, which is expected to challenge mpMRI-TB in the diagnosis of PCa.

Comparison of different laser-based enucleation techniques for benign prostate hyperplasia: A systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques. MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684). RESULTS: A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique (MD: -8.26, 95%CI: -12.73--3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique (MD:0.97,95%CI: -0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique (MD: -3.19, 95%CI: -7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD: 0.05, 95%CI: 0.00-0.10, p = 0.03; MD: 0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique (MD: 0.22, 95%CI: 0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe (MD: -0.12, 95%CI: -0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe (MD: -0.14, 95%CI: -0.56-0.29, p = 0.52). CONCLUSIONS: En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.

Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis.

BACKGROUND: To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). METHODS: We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [-2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). CONCLUSION: The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: A New Standard of Urinary Diversion.

Background: To summarize the current evidence on robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and compare perioperative outcomes and postoperative complications of patients undergoing RARC with extracorporeal urinary diversion (ECUD) and ICUD. Patients and Methods: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest. Also, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. Results: Thirteen studies with 4696 participants were included in this review. No significant differences were found between the ECUD and ICUD in operation time (OT) (mean difference [MD]: -6.45, 95% confidence interval [CI]: -35.20 to 22.30), length of stay (MD: 0.36, 95% CI: -0.81 to 1.54), 30-day overall complications (odds ratio [OR]: 0.92, 95% CI: 0.60-1.41), 30-day minor complications (OR: 1.36, 95% CI: 0.85-2.19), 30-day major complications (OR: 0.70, 95% CI: 0.34-1.43), 90-day overall complications (OR: 1.34, 95% CI: 0.83-2.18), and major complications (OR: 1.03, 95% CI: 0.68-1.57). However, less estimate blood loss (MD: 99.28 mL, 95% CI: 62.59-135.98), lower intraoperative blood transfusion (OR: 1.80, 95% CI: 1.09-2.95), shorter oral intake time (MD: 0.78, 95% CI: 0.43-1.14), and 90-day minor complications (OR: 1.72, 95% CI: 1.08-2.73) were associated with ICUD. The subgroup analysis showed less estimated blood loss (MD: 149.73, 95% CI: 21.33-278.13) and less OT (MD: 32.45, 95% CI: 14.37-50.53) were found in ICUD. Conclusions: The ICUD is a safe and feasible alternative to ECUD, which decreases the need for blood transfusion and reduces 90-day complications. However, further quality studies are needed to evaluate effectiveness of ICUD and its oncologic outcomes, functional outcomes, cost, and the quality of life.

Laparoscopic Versus Open Partial Nephrectomy: A Systemic Review and Meta-Analysis of Surgical, Oncological, and Functional Outcomes.

PURPOSE: To summarize and analyze the current evidence about surgical, oncological, and functional outcomes between laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN). MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis. Meanwhile, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 26 studies with 8095 patients were included. There was no statistical difference between the LPN and OPN in the terms of operation time (p=0.13), intraoperative complications (p=0.94), recurrence (p=0.56), cancer-specific survival (p=0.72), disease-free survival (p=0.72), and variations of estimated glomerular filtration rate (p=0.31). The LPN group had significantly less estimated blood loss (P<0.00001), lower blood transfusion (p=0.04), shorter length of hospital stay (p<0.00001), lower total (p=0.03) and postoperative complications (p=0.02), higher positive surgical margin (p=0.005), higher overall survival (p<0.00001), and less increased serum creatinine (p=0.002). The subgroup analysis showed that no clinically meaningful differences were found for T1a tumors in terms of operation time (p=0.11) and positive surgical margin (p=0.23). In addition, the subgroup analysis also suggested that less estimated blood loss (p<0.0001) and shorter length of hospital stay (p<0.00001) were associated with the LPN group for T1a tumors. CONCLUSIONS: This meta-analysis revealed that the LPN is a feasible and safe alternative to the OPN with comparable surgical, oncologic, and functional outcomes. However, the results should be applied prudently in the clinic because of the low quality of evidence. Further quality studies are needed to evaluate the effectiveness LPN and its postoperative quality of life compared with OPN.

The Relationship Between Hormone Replacement Therapy and Risk of Kidney Cancer in Women: A Meta-Analysis.

Results from the epidemiologic studies on the relationship between hormone replacement therapy (HRT) and the risk of kidney cancer in women were not completely consistent. This meta-analysis aimed to evaluate the relationship between HRT and risk of kidney cancer in women. We performed a meta-analysis of observational studies to assess this association. The PubMed and Embase databases were searched from their inception to January 29, 2020, to identify relevant studies that fit the pre-stated inclusion criteria; reference lists from the retrieved articles were also been reviewed. Relative risks (RRs) with corresponding 95% CIs were extracted and combined using random effects models. Furthermore, dose-response, sensitivity analyses, publication bias, and subgroup analysis by study design, regional location, and exposure assessment method were conducted. Thirteen articles involving 6 cohort studies and 8 case-control studies were included in our meta-analysis. Overall, 4194 women were diagnosed with kidney cancer among 648 107 participants. The pooled RR for kidney cancer was 1.08 (95% CI: 0.96-1.22) in those who were administered HRT compared to those who had not. Subgroup analysis indicated the overall result was not influenced by study type, regional location, or adjusted variables. Dose-response analysis showed a nonlinear relationship between HRT and kidney cancer (P = .0021) and the risk of kidney cancer decreased by 15% to 28% with 12 to 18 years of HRT use. No evidence of publication bias was found (P for Egger =.111). Our meta-analysis showed that HRT use is inversely associated with kidney cancer risk in a dose-dependent fashion.