Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients’ clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.
Background:The aim of this study was to assess the prognostic value of lymph node-associated variables, pN, lymph node ratio (LNR) and log odds (LODDS), in patients with bladder cancer.Methods: In the discovery cohort, 3358 patients with muscle-invasive bladder cancer (MIBC) and treated with radical cystectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database.A total of 173 patients with MIBC who underwent radical cystectomy at Shanghai Cancer Center between 2010 and 2013 were enrolled in the validation cohort.LNR and LODDS were calculated in two cohorts and prognostic value was compared between these two variables.Results: In the two cohorts, survival differences between LODDS, LNR and pN (from the 7 th AJCC TNM system) cohorts were statistically significant.Univariate and multivariate analyses confirmed that LNR and LODDS were independent prognostic factors and LODDS was better at predicting prognosis than pN and LNR for patients with MIBC.Moreover, LODDS had a better discriminative ability and model fit, proven by the highest Harrell's concordance index and lowest AIC among the three variables.Furthermore, scatter plots of pN, LNR and LODDS revealed that several groups of LNR and pN were heterogeneous and could be better stratified by LODDS in terms of prognosis estimation.Conclusion: LODDS has significant prognostic value for patients with MIBC.Moreover, LODDS is better at predicting prognosis for MIBC patients compared with pN and LNR.
Upper tract urothelial carcinoma (UTUC) accounts for 10% of urothelial carcinomas (UCs) and has a substantial hereditary component. However, the majority of our knowledge of germline spectrum comes from bladder cancer (BCa) data in White populations. Here, we sequence 309 Chinese UTUC cases and identify 71 germline pathogenic/likely pathogenic (P/LP) mutations in 62 patients (20.1%). Compared with White cases, we observe disparities and similarities in inherited mutational profiles. Association analysis reveals that germline P/LP mutations in MSH2, BRCA2, BRCA1, and BRIP1 significantly increase UTUC risk in Chinese populations. Furthermore, germline P/LP mutation in homologous recombination genes indicates poor prognosis for non-metastatic UTUC. Finally, we perform paired sequencing and observe significant correlations between germline mutation patterns and tumor subtypes. This study highlights the importance of genetic testing in patients with UTUC and calls for germline data from various ethnicities to better understand this disease.
Purpose Our study aims to examine the impact of definitive local therapy in prostate cancer patients with different metastatic sites. Methods Totally, 5,849 patients diagnosed with metastatic prostate carcinoma from 2010 to 2014 were selected from Surveillance, Epidemiology, and End Results (SEER). Log-rank analyses, multivariable regression analysis, and Kaplan–Meier methods were used to assess prognostic impact of local treatment in patients with different metastatic sites. Survival curves and forest plots were also plotted to describe the prognostic value of definitive local therapy. Results In our study, 159 patients received radical prostatectomy, and 62 received brachytherapy, while 5,628 did not receive local definitive local therapy. Survival analysis revealed that patients who received definitive local therapy had a better 5-year overall survival (OS) (P = 0.011) and cancer-specific survival (CSS) (P = 0.012). Multivariate regression analyses demonstrated that type of treatment was an independent prognostic indicator for OS (P = 0.011) and CSS (P = 0.012), along with age at diagnosis, chemotherapy, PSA level, and Gleason score. According to subgroup analysis, patients with bone metastasis or distant lymph node (LN) metastasis were significantly more likely to benefit from definitive local therapy. In addition, forest plots demonstrated that RP group had significant favorable OS and CSS in subgroups of younger age at diagnosis, T2–3 stage, N0–1 stage, Gleason score =7 or ≥8, bone metastasis, and distant LN metastasis. Conclusions Our study suggested that local therapy improved survival in prostate cancer patients with bone or distant LN metastasis. Furthermore, patients who were at T2–3 stage or Gleason score ≥7 also significantly benefit from definitive local therapy.
Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa. Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.
AGINGHowever, these treatments significantly reduce patient survival and quality of life [5,6].Thus, the mechanisms of BC should be investigated to effectively prevent progression.Circular RNAs (circRNAs) were discovered first in 1976 [7].Since then, various circRNAs have been identified [8].circRNAs constitute a conserved endogenous RNA spectrum, which are generated by back-splicing or exon skipping events.Many circRNAs
Objective To investigate the HPV DNA prevalence and genotype distribution among penile cancer in China. To identify association between HPV prevalence, different histological subtypes, tumor stage, tumor grade, demographics, comorbidity and phimosis incidence trend. Standardized HPV DNA detection and p16INK4a expression were used in a multi-center series of 340 penile squamous cell carcinomas diagnosed from 2006-2017. Materials and Methods HPV DNA detection and genotyping were examined by a validated kit for 23 different HPV subtypes (PCR-RDB HPV test). The cases with positive HPV DNA were additional tested for p16INK4a expression to confirm the HPV infection. Results Using the PCR-RDB HPV test, overall HPV prevalence was 48.8% (166/340) and that of p16INK4a expression was 45.6%. In this studied population, HPV16 was the most frequent HPV type detected in HPV-positive cancers (76.5%). HPV18 was the second most common type in penile cancers (15.1%). After pathology review, 307 cases were confirmed as invasive penile cancer, and the other 33 were non-invasive caners. The histologic subtypes of warty, basaloid, clear cell papillary, adenosquamaous and pseudohyperplastic were showed high HPV DNA prevalence. Among invasive cancers, no statistically significant differences in prevalence were observed by tumor grade, tumor stage or lymphnode stage at diagnosis. HPV positive penile cancer incidence significantly increase and the phimosis incidence significantly decrease from 2006 to 2017. Conclusions About a half of penile cancers were related to HPV infection. Our findings highlight the phimosis related penile cancers have been declining, the HPV related in the development of penile cancer and a fully aware of regional differences in HPV genotype distribution are tasks for penile cancer control and prevention.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)