Huihuang Li

Upper urinary tract urothelial carcinoma (UTUC) is aggressive and rare, often treated with radical nephroureterectomy (RNU). Neoadjuvant therapy (NAT) prior to RNU is increasingly explored to improve patient outcomes. This study aimed to update evidence on the efficacy of NAT in UTUC through a systematic review and meta-analysis focusing on survival indicators and pathological response rates. A comprehensive literature search across PubMed, Embase, Cochrane, and Web of Science up to October 2024 identified 31 eligible studies. Of these, 26 compared NAT to RNU alone, 4 compared NAT to adjuvant therapy (AT), and 1 included comparisons to both. Outcomes included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and pathological complete response (pCR). A total of 27 studies involving 9,195 UTUC patients showed that NAT + RNU significantly improved OS (HR = 0.46), RFS (HR = 0.56), CSS (HR = 0.45), and PFS (HR = 0.30) compared to RNU alone. The pCR rate in the NAT group was 10% versus 0% in the RNU group. Subgroup analysis showed slightly higher pCR rates in prospective than retrospective studies. Additionally, a meta-analysis of 5 studies (2,475 patients) showed that NAT did not improve OS compared to AT. However, NAT was associated with significantly better RFS, highlighting its potential in reducing recurrence. This meta-analysis supports NAT as a promising preoperative strategy in UTUC, with potential survival and pathological benefits.

Background: Although the durable efficacy of immune checkpoint inhibitors (ICIs) in BLCA has been confirmed in numerous studies, not all patients benefit from their application in the clinic. Platelets are increasingly being found to be closely associated with cancer progression and metastasis; however, their comprehensive role in BLCA remains unclear.Methods: We comprehensively explored platelet expression patterns in BLCA patients using an integrated set of 244 related genes. Correlations between these platelet patterns with tumor microenvironment (TME) subtypes, immune characteristics and immunotherapy efficacies were explored. In addition, a platelet risk score (PRS) was generated for individual prognosis and verified the ability to predict prognosis, precise TME phenotypes, and immunotherapy efficacies.Results: Genes were clustered into two patterns that represented different TME phenotypes and had the ability to predict immunotherapy efficacy. We constructed a PRS that could predict individual prognosis with satisfactory accuracy using TCGA-BLCA. The results remained consistent when PRS was validated in the GSE32894 and Xiangya cohort. Moreover, we found that our PRS was positively related to tumor-infiltrating lymphocytes (TILs) in the TCGA-BLCA and Xiangya cohort. As expected, patients with higher PRS exhibited more sensitive to immunotherapy than patients with lower PRS. Finally, we discovered that a high PRS indicated a basal subtype of BLCA, whereas a low PRS indicated a luminal subtype.Conclusion: Platelet-related genes could predict TME phenotypes in BLCA. We constructed a PRS that could predict the TME, prognosis, immunotherapy efficacy, and molecular subtypes in BLCA.

The gut microbiota is a large symbiotic community of anaerobic and facultative aerobic bacteria inhabiting the human intestinal tract, and its activities significantly affect human health. Increasing evidence has suggested that the gut microbiome plays an important role in tumor-related immune regulation. In the tumor microenvironment (TME), the gut microbiome and its metabolites affect the differentiation and function of immune cells regulating the immune evasion of tumors. The gut microbiome can indirectly influence individual responses to various classical tumor immunotherapies, including immune checkpoint inhibitor therapy and adoptive immunotherapy. Microbial regulation through antibiotics, prebiotics, and fecal microbiota transplantation (FMT) optimize the composition of the gut microbiome, improving the efficacy of immunotherapy and bringing a new perspective and hope for tumor treatment.

Background: Due to the different infiltration abundance of immune cells in tumor, the efficacy of immunotherapy varies widely among individuals. Recently, growing evidence suggested that cuproptosis has impact on cancer immunity profoundly. However, the comprehensive roles of cuproptosis-related genes in tumor microenvironment (TME) and in response to immunotherapy are still unclear.Methods: Based on 43 cuproptosis-related genes, we employed unsupervised clustering to identify cuproptosis-related patterns and single-sample gene set enrichment analysis algorithm to build a cuproptosis signature for individual patient’s immune cell infiltration and efficacy of immune checkpoint blockade (ICB) evaluation. Then, the cuproptosis-related genes were narrowed down using univariate Cox regression model and least absolute shrinkage and selection operator algorithm. Finally, a cuproptosis risk score was built by random survival forest based on these narrowed-down genes.Results: Two distinct cuproptosis-related patterns were developed, with cuproptosis cluster 1 showing better prognosis and higher enrichment of immune-related pathways and infiltration of immune cells. For individual evaluation, the cuproptosis signature that we built could be used not only for predicting immune cell infiltration in TME but also for evaluating an individual’s sensitivity to ICBs. Patients with higher cuproptosis signature scores exhibited more activated cancer immune processes, higher immune cell infiltration, and better curative efficacy of ICBs. Furthermore, a robust cuproptosis risk score indicated that patients with higher risk scores showed worse survival outcomes, which could be validated in internal and external validation cohorts. Ultimately, a nomogram which combined the risk score with the prognostic clinical factors was developed, and it showed excellent prediction accuracy for survival outcomes.Conclusion: Distinct cuproptosis-related patterns have significant differences on prognosis and immune cell infiltration in kidney renal clear cell carcinoma (KIRC). Cuproptosis signature and risk score are able to provide guidance for precision therapy and accurate prognosis prediction for patients with KIRC.

Background: Although the RNA modification N6-methyladenosine ZC3H13 has been found to play vital regulatory roles in many types of cancers, its role in predicting the tumor immune microenvironment (TME) and response to immune checkpoint blockade (ICB) in kidney renal clear cell carcinoma (KIRC) remains unclear. Methods: We comprehensively analyzed the expression, prognostic significance and immunological role of ZC3H13 in pan-cancers and systematically correlated ZC3H13 with TME cell-infiltration, ICB response and targeted therapy in KIRC. The data were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Broad Institute Cancer Cell Line Encyclopedia (CCLE) and DrugBank database. Also, we performed RNA sequencing (RNA-seq) of 46 renal cell carcinoma tissues and 11 adjacent normal tissues to validate our result. All analyses were implemented using R software, version 3.6.3. Results: ZC3H13 was significantly differentially expressed in most tumors. However, its expression profiles and prognostic significance were consistent only in KIRC, regardless of overall survival, progression-free survival and cancer-specific survival. Additionally, ZC3H13 expression was correlated with clinicopathological factors in KIRC. Furthermore, we found that ZC3H13 might shape a noninflamed phenotype and could predict a lower response to ICB in KIRC. These results could be validated in our own RNA-seq data. Tumor mutation burden (TMB) was significantly higher in the low ZC3H13 group. Finally, we found that ZC3H13 could predict the sensitivity of targeted therapy for KIRC. Conclusions: ZC3H13 might shape a noninflamed phenotype in KIRC. Moreover, ZC3H13 could predict the prognosis and clinical response of ICB and the sensitivity to targeted therapies in KIRC.

To evaluate current views on comparing delayed ligature of the dorsal venous complex (D-DVC) with standard ligature of the dorsal venous complex (S-DVC) for safety, urinary control and oncological outcomes during laparoscopic radical prostatectomy. A comprehensive searching of PubMed, Web of science, Embase and the Cochrane Library was made and then we performed a meta-analysis, including all randomized controlled trials (RCTs) and retrospective studies, to evaluate the two different techniques. Two RCTs and six retrospective studies containing 1822 cases (222 cases from RCTs and 1600 cases from retrospective studies) were identified. Although D-DVC was related to more blood loss (WMD: 7.30 mL; 95% CI, 2.43 to 12.16; p = 0.003), the blood transfusion rate between the two groups showed no significant difference (OR = 1.93; 95% CI, 0.55 to 6.73; p = 0.31), and patients in the D-DVC group could benefit from a shorter operative time (WMD: -30.83 min; 95% CI, -53.32 to -8.35; p = 0.007). Positive apical margin events were significantly less in the D-DVC group (OR = 0.39; 95% CI, 0.22 to 0.71; p = 0.002). As for urinary control, there were no differences in continence rates after 3 months (OR = 1.64; 95% CI, 0.98 to 2.73; p = 0.06) and 12 months (OR = 1.00; 95% CI, 0.63 to 1.57; p = 0.99) of follow-up. However, there was a significantly higher continence rate after 6 months of follow-up in the D-DVC group (OR = 1.46; 95% CI, 1.02 to 2.11; p = 0.04). Standard and delayed approaches to DVC are equally safe and result in similar urinary control. The delayed approach could decrease the positive apical margin rate. However, further large-scale prospective studies are needed to investigate and compare the prognosis and long-term functional outcomes between the two approaches.

Purpose To examine the possible prognostic factors in patients with type 1 and type 2 papillary renal cell carcinoma (pRCC) after surgical management and to identify the independent predictive factors of the prognosis. Methods From 2010 to 2017, 1405 patients underwent surgery for renal cell carcinoma, of whom 114 had type 1 or type 2 pRCC and follow-up data were available for 88 patients. Clinicopathological and prognostic parameters were compared between type 1 and type 2 pRCC. Possible prognostic factors were retrospectively analyzed by univariate and multivariate analyses with Cox regression. Results The study included 63 males and 25 females with a mean age of 54.27 ± 12.91. 53 patients were diagnosed by regular physical examination and others presented with hematuria or lumbago. 53 (60.2%) underwent radical nephrectomy and 35 (39.8%) underwent nephron sparing surgery. After a mean follow-up of 46.08 ± 22.65 months, 16 patients died of pRCC metastasis and the 5-year disease-specific survival was 79.3%. The comparison of the 39 (44.3%) type 1 and 49 (55.7%) type 2 pRCCs revealed that type 2 pRCC had significantly higher grade and worse prognosis. Univariate analysis showed that symptomatic diagnosis, type, grade, and tumor stage were prognostic factors. Multivariate analysis identified that type and tumor stage were independent factors of the prognosis. Conclusions Pathological type and tumor stage could serve as independent factors for the prognosis of patients with pRCC.