Ultrasensitive optical fiber SPR sensor enhanced by Au-NPs-film modified with functionalized CQDs for label-free detecting cobalt (II) ion.

BACKGROUND: Cobalt, an essential trace element, is vital for maintaining human nervous system function, aiding in DNA synthesis, and contributing to red blood cell production. It is helpful for disease diagnosis and treatment plan evaluation by precisely monitoring its concentration changes in the human body. Despite extensive efforts made, due to its ultra-low concentration, the current limit of detection (LOD) as reported is still inadequate and cannot be satisfied with the precise clinical applications. Therefore, it is crucial to develop novel label-free sensors with high sensitivity and excellent selectivity for detecting trace amounts of Co2+. RESULTS: Here, an ultrasensitive optical fiber SPR sensor was designed and fabricated for label-free detection of Co2+ with ultra-low concentration. It is achieved by modifying the carboxyl-functionalized CQDs on the AuNPs/Au film-coated hetero-core fiber, which can specifically capture the Co2+, leading to changes in the fiber's surface refractive index (RI) and subsequent SPR wavelength shifts in the transmission spectrum. Both the Au film and AuNPs on the fiber are modified with CQDs, leveraging their large surface area to enhance the number of active sites and probes. The sensor exhibits an ultra-high sensitivity of approximately 6.67 × 1019 nm/M, and the LOD is obtained as low as 5.36 × 10-20 M which is several orders of magnitude lower compared to other conventional methods. It is also experimentally demonstrated that the sensor possesses excellent specificity, stability, and repeatability, which may be adapted for detecting real clinical samples. SIGNIFICANCE: The CQDs-functionalized optical fiber SPR sensor exhibits substantial potential for precisely detecting Co2+ of trace amounts, which is especially vital for scarce clinical samples. Additionally, the sensing platform with sample sensor fabrication and measurement configuration introduces a novel, highly sensitive approach to biochemical analysis, particularly adapting for applications involving the detection of trace targets, which could also be employed to detect various biochemical targets by facile modification of CQDs with specific groups or biomolecules.

Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.

Prostate cancer (PCa) is the most common malignant tumor in men. Currently, there are few prognosis indicators for predicting PCa outcomes and guiding treatments. Here, we perform comprehensive proteomic profiling of 918 tissue specimens from 306 Chinese patients with PCa using data-independent acquisition mass spectrometry (DIA-MS). We identify over 10,000 proteins and define three molecular subtypes of PCa with significant clinical and proteomic differences. We develop a 16-protein panel that effectively predicts biochemical recurrence (BCR) for patients with PCa, which is validated in six published datasets and one additional 99-biopsy-sample cohort by targeted proteomics. Interestingly, this 16-protein panel effectively predicts BCR across different International Society of Urological Pathology (ISUP) grades and pathological stages and outperforms the D'Amico risk classification system in BCR prediction. Furthermore, double knockout of NUDT5 and SEPTIN8, two components from the 16-protein panel, significantly suppresses the PCa cells to proliferate, invade, and migrate, suggesting the combination of NUDT5 and SEPTIN8 may provide new approaches for PCa treatment.

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Polyacrylic Acid/Polyaniline-Coated Multimode Interferometer for Ammonia Detection.

A coaxial optical fiber interferometer (COFI) is proposed here for ammonia sensing, which comprises two light-carrying single-mode fibers (SMF) fused to a section of no-core fiber (NCF), thus forming an optical interferometer. The outer surface of the COFI is coated with a layer of polyacrylic acid (PAA)/polyaniline (PAni) film. The refractive index (RI) of the sensitive layer varies when PAA/PAni interacts with ammonia, which leads to the resonance wavelength shift. The surface morphology and structure of the PAA/PAni composites were characterized by using a scanning electron microscope (SEM) and Fourier-transform infrared (FTIR) spectroscopy. When the sensor was exposed to an ammonia atmosphere of different concentrations at room temperature, the sensing performance of the PAA/PAni composite film was superior to that of a sensitive film formed by single-component PAA or PAni. According to the experimental results, the composite film formed by 5 wt% PAA mixed with 2 wt% PAni shows better performance when used for ammonia sensing. A maximum sensitivity of 9.8 pm/ppm was obtained under the ammonia concentration of 50 ppm. In addition, the sensor shows good performance in response time (100 s) and recovery time (180 s) and has good stability and selectivity. The proposed optical fiber ammonia sensor is adapted to monitor leakage in its production, storage, transportation, and application.

Advanced Integration of Glutathione-Functionalized Optical Fiber SPR Sensor for Ultra-Sensitive Detection of Lead Ions.

It is crucial to detect Pb2+ accurately and rapidly. This work proposes an ultra-sensitive optical fiber surface plasmon resonance (SPR) sensor functionalized with glutathione (GSH) for label-free detection of the ultra-low Pb2+ concentration, in which the refractive index (RI) sensitivity of the multimode-singlemode-multimode (MSM) hetero-core fiber is largely enhanced by the gold nanoparticles (AuNPs)/Au film coupling SPR effect. The GSH is modified on the fiber as the sensing probe to capture and identify Pb2+ specifically. Its working principle is that the Pb2+ chemically reacts with deprotonated carboxyl groups in GSH through ligand bonding, resulting in the formation of stable and specific chelates, inducing the variation of the local RI on the sensor surface, which in turn leads to the SPR wavelength shift in the transmission spectrum. Attributing to the AuNPs, both the Au substrates can be fully functionalized with the GSH molecules as the probes, which largely increases the number of active sites for Pb2+ trapping. Combined with the SPR effect, the sensor achieves a sensitivity of 2.32 × 1011 nm/M and a limit of detection (LOD) of 0.43 pM. It also demonstrates exceptional specificity, stability, and reproducibility, making it suitable for various applications in water pollution, biomedicine, and food safety.

Rapid-Response and Wide-Range pH Sensors Enabled by Self-Assembled Functional PAni/PAA Layer on No-Core Fiber.

The measurement of pH has received great attention in diverse fields, such as clinical diagnostics, environmental protection, and food safety. Optical fiber sensors are widely used for pH sensing because of their great advantages. In this work, an optical fiber pH sensor is fabricated, by combining the merits of the multimode interference configuration and pH-sensitive polyaniline/polyacrylic acid (PAni/PAA) coatings, which was successfully in situ deposited on the no-core fiber (NCF) by the layer-by-layer (LBL) self-assembly method. The sensors' performance was experimentally characterized when used for pH detection. It has a high sensitivity of 0.985 nm/pH and a great linear response in a universal pH range of 2-12. The response time and recovery time is measured to be less than 10 s. In addition, its temperature sensitivity is tested to be about 0.01 nm/°C with a low temperature crosstalk effect, which makes it promising for detecting pH in the liquid phase with temperature variation. The sensors also demonstrated easy fabrication, good stability, and repeatability, which are adapted to pH detection in most practical applications.

Propensity-matched pair analysis of safety and efficacy between laparoscopic and open radical nephrectomy for the treatment of large renal masses (>10 cm): a retrospective cohort study.

Background: Open radical nephrectomy (ORN) is a practical procedure for treating patients with large renal carcinomas >10 cm in size, and few studies have focused on feasibility and safety of laparoscopic radical nephrectomy (LRN). The current study was to assess the safety and effectiveness of LRN and ORN in large renal carcinoma patients by propensity matched pair analysis. Methods: In this cohort study, a retrospective review of radical nephrectomy data from October 2010 to October 2018 at Changhai Hospital was conducted. Patients with renal carcinomas >10 cm in size by pre-operative images were included. Patients' demographics including age, gender, body mass index (BMI), tumor size, operation time, hospitalization days, etc. were collected. Renal tumor patients undergoing LRN or ORN were match-paired by gender, BMI, age, and tumor size. Peri-operative outcomes including estimated blood loss and complications were compared. The follow-up contents included survival time, disease progression, and cause of death, and cancer-specific and progression-free survival were estimated via Kaplan-Meier curve analysis. Results: Among 92 patients with clinical T2b renal masses, 37 pairs were matched. The average tumor sizes of the LRN and ORN groups were 11.37±0.30 and 11.67±0.33 cm (P=0.375), respectively. The average operating time for LRN was slightly longer (204.32±11.17 vs. 192.78±8.50 min, P=0.414). Estimated blood loss (EBL) (336.49±63.58 mL for LRN vs. 545.95±74.52 mL for ORN, P=0.036), the length of postoperative stay [6.0 (5.0-9.0) for LRN vs. 9.0 (6.0-11.5) days for ORN, P=0.015], and removal time of the drainage tube [4.0 (3.0-5.0) days for LRN vs. 5.0 (4.0-6.0) for ORN, P<0.001] were less than in the LRN group. The pathological subtype and Fuhrman grade were comparable. Both groups were followed up for a similar period, and no difference was observed in 5-year survival rates. Conclusions: Considering the conversion rates and overall complication rates, it seems that LRN for large renal carcinomas demonstrated equivalent peri-operative safety and effectiveness compared with ORN, with no adverse effects on midterm oncological outcomes.

Tracing and Forecasting Metabolic Indices of Cancer Patients Using Patient-Specific Deep Learning Models.

We develop a patient-specific dynamical system model from the time series data of the cancer patient's metabolic panel taken during the period of cancer treatment and recovery. The model consists of a pair of stacked long short-term memory (LSTM) recurrent neural networks and a fully connected neural network in each unit. It is intended to be used by physicians to trace back and look forward at the patient's metabolic indices, to identify potential adverse events, and to make short-term predictions. When the model is used in making short-term predictions, the relative error in every index is less than 10% in the L∞ norm and less than 6.3% in the L1 norm in the validation process. Once a master model is built, the patient-specific model can be calibrated through transfer learning. As an example, we obtain patient-specific models for four more cancer patients through transfer learning, which all exhibit reduced training time and a comparable level of accuracy. This study demonstrates that this modeling approach is reliable and can deliver clinically acceptable physiological models for tracking and forecasting patients' metabolic indices.

Effect of APOBEC3A functional polymorphism on renal cell carcinoma is influenced by tumor necrosis factor-α and transcriptional repressor ETS1.

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) 3 cytidine deaminases are the prominent drivers of somatic mutations in cancers. However, the effect of APOBEC3s functional polymorphisms on the development of renal cell carcinoma (RCC) remains unknown. Five genetic polymorphisms affecting the expression of APOBEC3A (A3A), APOBEC3B, and APOBEC4 and uracil DNA glycosylase (UNG) were genotyped in 728 RCC patients and 1500 healthy controls. The effects of tumor necrosis factor-α (TNFα) and interleukin-6 on the activity of the A3A promoter with rs12157810-A or -C in four RCC cell lines (786-O, A498, Caki2, ACHN) and two colorectal cancer cell lines (HCT116, SW620) were evaluated using dual-luciferase assays. Transcriptional repressors to the A3A promoter were identified by chromatin immunoprecipitation-quantitative PCR. The proapoptotic effect of A3A on RCC cells was evaluated using cytometry. The prognostic values of A3A and ETS1 were evaluated by the Cox regression analysis. The expressions of A3A and ETS1 were evaluated in clear cell RCC (ccRCC) specimens with different polymorphic genotypes using quantitative RT-PCR and immunohistochemistry. Of those functional polymorphisms, CC genotype at rs12157810 in the A3A promoter was significantly associated with a decreased risk of ccRCC, compared to the AA genotype (odds ratio adjusted for age and gender, 0.41, 95% confidence interval [CI], 0.28-0.57). Other polymorphic genotypes were not associated with the risk of RCC. The activity of the A3A promoter with rs12157810-C was significantly higher than that with rs12157810-A in the four RCC cell lines and two colorectal cancer cell lines. The activity of the A3A promoter with rs12157810-C was greatly up-regulated by TNFα and predominantly inhibited by a transcriptional repressor ETS1. The binding of ETS1 to the A3A promoter with rs12157810-C was looser than that with rs12157810-A. Ectopic expression of A3A significantly promoted apoptosis in ccRCC cells, rather than in colorectal cancer cells. Higher ETS1 expression predicted a favorable prognosis in ccRCC, with a hazard ratio of 0.58 (95% CI, 0.43-0.78). Rs121567810-C up-regulates the A3A promoter activity, possibly due to higher response to TNFα and looser transcriptional repression by ETS1. Up-regulation of A3A increases apoptosis, thus decreasing ccRCC risk in those carrying rs121567810-C.

Preclinical profile and phase I clinical trial of a novel androgen receptor antagonist GT0918 in castration-resistant prostate cancer.

PURPOSE: We conducted preclinical experiments and phase I clinical trial to investigate the safety, pharmacokinetics (PK) and antitumour effects of GT0918 in castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: An androgen receptor (AR) competitive binding assay was performed, followed by evaluation of GT0918 on AR protein expression. The efficacy of GT0918 was investigated in a castration-resistant xenograft model. A phase I dose-escalation study of GT0918 in CRPC was also carried out to evaluate its safety, PK and antitumour efficacy. RESULTS: GT0918 was demonstrated to inhibit the binding of androgen to AR more potently than MDV3100, and to effectively reduce the AR protein level. GT0918 inhibited the transcriptional activity of wild-type AR and AR with clinically relevant ligand-binding domain mutations. Furthermore, GT0918 significantly inhibited the growth of prostate cancer. A total of 16 patients was treated with GT0918 at five dose levels. Among these 16 patients, 10 and 2 patients, respectively, completed a three-cycle and six-cycle treatment, in which MTD was not reached. All the treatment-related adverse events were grade I, including hypercholesterolemia, hypertriglyceridemia, fatigue and anaemia. PK parameters showed that drug exposure increased with dose proportionally from 50 to 300 mg and a saturation was observed between 300 and 400 mg. PSA declines of ≥30% and ≥50% were, respectively, observed in six and two cases. All the 12 patients with metastatic soft tissue lesions confirmed stable disease. CONCLUSIONS: GT0918, a full AR antagonist without agonist effect, has high binding affinity to AR with AR protein down-regulation activity. GT0918 is demonstrated to be well tolerated with a favourable PK profile and exhibits promising antitumour activity in CRPC. CLINICALTRIALS: gov identifier CTR20150501.

Molecular molds for regularizing Kondo states at atom/metal interfaces.

Adsorption of magnetic transition metal atoms on a metal surface leads to the formation of Kondo states at the atom/metal interfaces. However, the significant influence of surrounding environment presents challenges for potential applications. In this work, we realize a novel strategy to regularize the Kondo states by moving a CoPc molecular mold on an Au(111) surface to capture the dispersed Co adatoms. The symmetric and ordered structures of the atom-mold complexes, as well as the strong dπ-π bonding between the Co adatoms and conjugated isoindole units, result in highly robust and uniform Kondo states at the Co/Au(111) interfaces. Even more remarkably, the CoPc further enables a fine tuning of Kondo states through the molecular-mold-mediated superexchange interactions between Co adatoms separated by more than 12 Å. Being highly precise, efficient and reproducible, the proposed molecular mold strategy may open a new horizon for the construction and control of nano-sized quantum devices.

A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

Development and external validation of a nomogram predicting prognosis of upper tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVE: To create multivariable models with readily available clinicopathologic variables for predicting the prognosis of upper tract urothelial carcinomas (UTUC). PATIENTS AND METHODS: We retrospectively analyzed patients diagnosed as UTUC and underwent radical nephroureterectomy in 2 high volumes, tertiary care centers. A total of 445 patients and 227 patients met the inclusion criteria were included for constructing the prediction model and external validation, respectively. Univariable and multivariable Cox regression models were used to analyze independent risk factors, and nomogram and calibration curve were constructed by R project. RESULTS: The median follow-up for the development and external validation cohorts were 33.5 and 32.5 months, respectively. Multivariable analysis detected older age (≥65 years), with concurrent bladder cancer at diagnosis, with both ureter and renal pelvic tumor, lymphovascular invasion, urothelial carcinoma with divergent differentiation, higher pathological grade and stage, and positive lymph node were significantly associated with poorer outcome of UTUC. The c-index of the nomogram with these above-mentioned independent risk factors to predict the cancer specific survival was 0.74 (95% CI, 0.64-0.84) and 0.73 (95%CI, 0.59-0.87) for the development cohort and external validation cohort, respectively. CONCLUSIONS: We developed and externally validated a novel and accurate nomogram with readily available clinicopathological information for predicting the cancer specific survival of UTUC. This nomogram could help clinicians stratify patients with UTUC into different risk groups with distinct prognosis by the total scores obtained from the prediction tool, thus facilitate decision-making and clinical trial designing.

Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma.

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS: FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.

Quantum Control of Graphene Plasmon Excitation and Propagation at Heaviside Potential Steps.

Quantum mechanical effects of single particles can affect the collective plasmon behaviors substantially. In this work, the quantum control of plasmon excitation and propagation in graphene is demonstrated by adopting the variable quantum transmission of carriers at Heaviside potential steps as a tuning knob. First, the plasmon reflection is revealed to be tunable within a broad range by varying the ratio γ between the carrier energy and potential height, which originates from the quantum mechanical effect of carrier propagation at potential steps. Moreover, the plasmon excitation by free-space photos can be regulated from fully suppressed to fully launched in graphene potential wells also through adjusting γ, which defines the degrees of the carrier confinement in the potential wells. These discovered quantum plasmon effects offer a unified quantum-mechanical solution toward ultimate control of both plasmon launching and propagating, which are indispensable processes in building plasmon circuitry.

Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression.

BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses. RESULTS AND LIMITATIONS: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated. CONCLUSIONS: There are shared and salient genetic characteristics of PCa in Chinese and Caucasian men. Novel genetic alterations in PCDH9 and PLXNA1 were associated with disease progression. PATIENT SUMMARY: We reported the first large-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment.

Prostate cancer antigen 3 moderately improves diagnostic accuracy in Chinese patients undergoing first prostate biopsy.

Prostate cancer antigen 3 (PCA3) is a biomarker for diagnosing prostate cancer (PCa) identified in the Caucasian population. We evaluated the effectiveness of urinary PCA3 in predicting the biopsy result in 500 men undergoing initial prostate biopsy. The predictive power of the PCA3 score was evaluated by the area under receiver operating characteristic (ROC) curve (AUC) and by decision curve analysis. PCA3 score sufficed to discriminate positive from negative prostate biopsy results but was not correlated with the aggressiveness of PCa. The ROC analysis showed a higher AUC for the PCA3 score than %fPSA (0.750 vs 0.622, P = 0.046) in patients with a PSA of 4.0-10.0 ng ml-1 , but the PCA3-based model is not significantly better than the base model. Decision curve analysis indicates the PCA3-based model was superior to the base model with a higher net benefit for almost all threshold probabilities, especially the threshold probabilities of 25%-40% in patients with a PSA of 4.0-10.0 ng ml-1 . However, the AUC of the PCA3 score (0.712) is not superior to %fPSA (0.698) or PSAD (0.773) in patients with a PSA >10.0 ng ml-1 . Our results confirmed that the RT-PCR-based PCA3 test moderately improved diagnostic accuracy in Chinese patients undergoing first prostate biopsy with a PSA of 4.0-10.0 ng ml-1 .

The development of plasma pseudotargeted GC-MS metabolic profiling and its application in bladder cancer.

Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20 %. The Pearson correlations of 90.7 and 78.3 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3 % of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling. Graphical abstract The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination.

A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression.

Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190-3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052-6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues.