Search

Objectives: To develop nomograms predicting the incidence of castration‐resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (PCa). Patients and Methods: Data from 449 patients with de novo metastatic PCa were retrospectively analysed. Patients were randomly divided into a training (n = 314, 70%) and a validation cohort (n = 135, 30%). Predictive factors were selected using a Cox proportional hazards model and were further used for building predictive models. The outcomes were incidence of CRPC and OS. Results: Predictive factors included: Gleason score (GS), intraductal carcinoma of the prostate (IDC‐P), Eastern Cooperative Oncology Group status, and alkaline phosphatase, haemoglobin and prostate‐specific antigen levels. IDC‐P and GS were the strongest prognosticators for both the incidence of CRPC and OS. Nomograms for predicting CRPC and OS had an internal validated concordance index of 0.762 and 0.723, respectively. Based on the β coefficients of the final model, risk classification systems were constructed. For those with favourable, intermediate and poor prognosis, the median time to CRPC was 62.6, 28.0 and 13.0 months (P < 0.001), respectively; and the median OS was not reached, 55.0 and 33.0 months, respectively (P < 0.001). Conclusions: We developed two novel nomograms to predict the incidence of CRPC and OS for patients with de novo metastatic PCa. These tools may assist in physician decision‐making and the designing of clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking., Experimental Design: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis., Results: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy., Conclusions: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation., (©2024 The Authors; Published by the American Association for Cancer Research.)

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P., Significance: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies., (©2023 American Association for Cancer Research.)

In this work, we reported a sensitive, label-free electrochemical biosensor based on the intrinsic topological insulator (TI) BiSbTeSe 2 for potential application in the determination of the HIV gene. With strong spin-obit coupling, TIs could have robust surface states with low electronic noise, which might be beneficial for the stable and sensitive electron transport between the electrode and electrolyte interface. Under optimized conditions of the biosensors using BiSbTeSe 2 , the differential pulse voltammetry (DPV) peak currents showed a linear relationship with the logarithm of target DNA concentrations ranging from 1.0 × 10 -13 to 1.0 × 10 -7 M, with a detection limit of 1.07 × 10 -15 M. The sensing assay also displayed good selectivity and stability after storage at 4 °C for 7 days. This work provides an effective way to develop biosensors with topological materials, which have a potential application in the clinical determination and monitoring field.

Tumor-infiltrating immune cells have been recognized to be associated with prognosis and response to immunotherapy; however, genes related to immune microenvironment of clear cell renal cell carcinoma (ccRCC) remains unclear. To better understand the effects of genes involved in immune and stromal cells on prognosis, we used Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), DAVID database and ESTMATE algorithm, and divided the patients into low and high groups according to immune (median: 1038.45) and stromal scores (median: 667.945), respectively. We found the immune scores were significantly correlated with clinicopathological parameters and overall survival (OS). Based on immune scores, 890 DEGs were significantly associated with OS among the 1433 up-regulated genes. Based on top 10 DEGs (IL10RA, FCER1G, SASH3, TIGIT, RHOH, IL12RB1, AIF1, LPXN, LAPTM5 and SP140), cases with number of up-regulated genes ≥ 5 were associated poor OS (P = 0.002). In addition, the mean differences of percentages of CD8 T cells (11.32%), CD4 memory resting T cells (-4.52%) and mast resting cells (-3.55%) between low and high immune scores were the most significant. Thus, combination of these genes might use to predict the efficacy of immunotherapy. Further analyses of these genes were warrant to explore their potential association with the prognosis of ccRCC., Competing Interests: None., (AJTR Copyright © 2020.)

Herein an ultrasensitive photoelectrochemical (PEC)/visual biosensor coupled with a multiple signal amplification strategy was proposed for the detection of nucleic acids. The initial signal amplification was achieved via ternary AgInSe 2 quantum dot (QD)-sensitized ZnO nanoflowers (ZnO NFs) to form an excellent photoelectric layer. A gold-modified nanorod-anchored CeO 2 (Au@NR-CeO 2 ) octahedron was introduced as a multifunctional signal regulator via the formation of triple helix molecules. The Au@NR-CeO 2 octahedron could not only quench the photocurrent signal due to the competitive capture of photon energy and electron donors with the photoelectric layer but could also act like a peroxidase to catalyze the formation of mimetic enzymatic catalytic precipitation (MECP) on the surface of the photoelectric layer. Furthermore, the steric hindrance effect from the Au@NR-CeO 2 octahedron further reduced the output of the photocurrent signal. After incubation with t-DNA, the triple helix conformation was disassembled and the Au@NR-CeO 2 octahedron was released from the electrode surface, leading to the significant increase of photocurrent signal. Meanwhile, the released Au@NR-CeO 2 octahedron could flow into the colorimetric area of the lab-on-paper device to catalyze the occurrence of the color reaction, achieving a visual detection for t-DNA. On the basis of the multiple signal amplification strategy, t-DNA was detected specifically with a lower limit of detection of 0.28 fM and a wider linear range from 0.5 fM to 50 nM. The proposed method has the potential utility to detect a variety of nucleic acids and biomarkers.

We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer (PCa). Outcomes included the duration of castration-resistant prostate cancer-free survival (CFS) and overall survival (OS). Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score (GS) groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 + 4 and GS 4 + 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS (P = 0.321). However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.