Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. This study aimed to develop and validate a regulatory T cell (Treg)-associated magnetic resonance imaging (MRI) radiomics model and assess its prognostic value, cross-species similarity, and interpretability across multicenter cohorts. Tregs retained prognostic significance for patients with GBM under World Health Organization CNS 5 classification. In murine models, Treg depletion suppressed tumor growth and reduced the infiltration of myeloid-derived suppressor cells, tumor-associated macrophages, and exhausted CD8+T cells. The in vitro co-culture of Tregs with GL261 cells significantly reduced radiation-induced apoptosis. We constructed a Treg-associated radiomics model comprising six features and validated the prognostic value of the radiomics score (RS) across multicenter clinical imaging cohorts (First Affiliated Hospital of Fujian Medical University, n = 111, hazard ratio [HR] = 2.178, 95% confidence interval [CI]: 1.269-3.740; Second Affiliated Hospital of Zhejiang University School of Medicine, n = 126, HR = 1.664, 95% CI: 1.049-2.640; The Cancer Genome Atlas, n = 86, HR = 1.811, 95% CI: 1.089-3.010). Treg depletion experiments also confirmed causal associations between two radiomic features and Treg infiltration. RS stratification correlated with hypoxia, glycolysis, interleukin (IL)-2/signal transducer and activator of transcription (STAT) 5, and IL-6/Janus kinase/STAT3 signaling pathways and immune checkpoints and genomic alterations. The MRI radiomics model enables noninvasive prediction of Treg infiltration and serves as a robust, generalizable prognostic biomarker for GBM. These findings provide evidence for biological causal associations and cross-species similarities between radiomics features and Treg infiltration.

Immune-like coordinated cell death (CCD) indirectly eliminates target cells via immune activation, bypassing intrinsic programmed cell death. Using RNAi screening in a Drosophila tumor model, we identified a series of genes capable of inducing CCD. Here, we characterize adhesion G protein-coupled receptor ADGRL1 as a key mediator that activates anti-tumor immunity by facilitating cDC1-CD8+ T cell hub formation, as revealed by single-cell transcriptomics. Mechanistically, ADGRL1 ablation activates type I interferon signaling and promotes JAK/STAT1-dependent Decorin secretion, mediated by disrupting the GSK3β/β-catenin pathway. Clinical and database analyses validate ADGRL1 as a promising therapeutic target, and its deletion synergizes with PD-1 blockade to strongly suppress tumor growth. Furthermore, via virtual small molecule screening combined with DARTS (drug affinity responsive target stability), we identify an ADGRL1-targeting compound that demonstrates antitumor efficacy in vivo. Together, our findings reveal an immunoregulatory role for ADGRL1 and highlight its therapeutic potential in cancer treatment.

Background:In clear cell renal cell carcinoma (ccRCC), mast cell activation and angiogenesis are crucial for disease progression, with interactions occurring between these processes. The involvement of mast cell-related angiogenic characteristics in ccRCC is not yet fully elucidated. To address this gap, this study aims to clarify the biological role and prognostic significance of mast cell-mediated angiogenesis in ccRCC, and to examine its links to the tumor microenvironment and disease progression. Methods:We utilized bioinformatics techniques to integrate and analyze single-cell and bulk transcriptomics data. We developed prognostic models using ten classical machine learning algorithms and conducted intergroup differential gene extraction, functional pathway enrichment, immune infiltration, and somatic mutation analyses. Finally, the expression levels of the model genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results:TNF-α signaling is significantly upregulated in mast cells within the ccRCC microenvironment, shaping an immunosuppressive microenvironment through receptor-ligand interactions such as SPP1-CD44 and CLEC2C-KLRB1. We developed a mast cell-associated angiogenesis score that demonstrates satisfactory accuracy in assessing prognosis for ccRCC patients. Patients in the high-risk group exhibited activation of oncogenic signaling pathways including JAK-STAT3, accompanied by immunosuppressive status and elevated genomic instability. Furthermore, we identified the core oncogene TIMP1 and the protective gene EMCN. Conclusions:Mast cell-associated angiogenesis features aid in prognostic assessment for ccRCC patients, with TIMP1 and EMCN representing potential therapeutic targets.

Exposomics provides a systems-level framework to characterize the environmental exposures experienced across the life course and their biological consequences, offering critical insights into tumor initiation and precision prevention. Advances in sensing technologies, intelligent materials, and data science now enable continuous acquisition of external exposures alongside endogenous molecular and phenotypic responses. In this emerging paradigm, exposure is conceptualized not as an isolated variable statistically associated with disease, but as a temporally structured driver embedded within multiscale biological processes. By integrating multimodal monitoring with AI-enabled causal modeling, exposomics moves cancer risk assessment beyond population averages toward individualized, dynamically updated exposure-informed risk assessment. This Perspective highlights key technological directions in external-internal monitoring integration, intelligent sensing ecosystems, and causal data fusion, and outlines a translational framework aimed at supporting precision cancer prevention and early risk management.

Background:The causal association of insomnia with multiple urological and reproductive conditions still lacks clarity. Our aim was to assess this relationship by examining impact of insomnia on 10 urological and reproductive conditions using Mendelian randomization (MR) designs. Methods:Summary statistics for insomnia and 10 urological and reproductive conditions were acquired from the UK Biobank, 23andMe, FinnGen, and genetic consortia. Inverse variance weighted approach was utilized as the main MR analysis. Sensitivity analyses were performed employing MR-PRESSO (Pleiotropy Residual Sum and Outlier), maximum likelihood, MR-Egger, and weighted median methods to examine the robustness of the estimates. Results:Genetically determined insomnia showed an elevated risk of cystitis [odds ratio (OR) =1.81; 95% confidence interval (CI): 1.47-2.24; P<0.001], and prostatitis (OR =3.53; 95% CI: 1.73-7.18; P<0.001) after Bonferroni correction. Suggestive evidence of an association was found between insomnia and a heightened risk of prostate cancer (OR =1.30; 95% CI: 1.00-1.67; P=0.046), alongside a decreased risk of bladder cancer (OR =0.48; 95% CI: 0.26-0.90; P=0.02). No causal effects were observed for kidney cancer, kidney and ureter calculus, neurogenic bladder, benign prostatic hyperplasia (BPH), male infertility, or female infertility. Conclusions:Findings support insomnia as a potential causal risk factor for cystitis and prostatitis. This highlights insomnia as an important target for reducing the risk of these diseases.

The clinical success of PD-1/PD-L1 blockade has revolutionized cancer immunotherapy. However, the issues of immune resistance have become increasingly prominent, representing a critical limitation in modern oncology. This phenomenon has prompted efforts to elucidate the mechanisms underlying both types of resistance and to find breakthrough therapeutic strategies. This article provides a comprehensive overview of PD-1/PD-L1 blockade resistance mechanisms from both primary and acquired resistance perspectives, including tumor intrinsic factors, immune microenvironment components, and systemic factors. Building on this foundation, emerging research demonstrates that type I interferons (IFNs), particularly IFN-α and IFN-β, play crucial immunomodulatory roles in overcoming resistance to PD-1/PD-L1 blockade. We delineate six molecular mechanisms through which IFN-α/β enhance PD-1/PD-L1 blockade efficacy, and innovative strategies are proposed to therapeutically boost IFN-α/β production, including gene editing techniques, targeting the cGAS-STING or TLR pathway and so on. Furthermore, insights into current challenges and future directions of the application of IFN-α/β to improve PD-1/PD-L1 blockade are discussed. This review holds significant academic value by not only synthesizing current knowledge on PD-1/PD-L1 resistance mechanisms but also pioneering a framework for leveraging type I IFNs to overcome these barriers.

Aims The association of sleep traits (insomnia, sleep duration, chronotype, daytime sleepiness, and snoring) with benign prostatic hyperplasia (BPH) is unclear. This research aimed to examine the effects of sleep traits on BPH risk. Methods A total of 170 241 men aged 38 to 73 years from UK Biobank were included. An overall healthy sleep score was created based on five sleep traits. A Cox regression model was utilized to compute adjusted hazard ratios (HRs) and population attributable fractions (PAFs) with 95% confidence intervals (CIs) for BPH risk in relation to sleep traits. Results During a median of 12.0 years follow‐up, 13 026 incident BPH cases occurred. We observed that sleep duration (7–8 h/d; HR 0.95; 95% CI 0.92–0.99), no frequent insomnia (HR 0.71; 95% CI 0.69–0.74), and no frequent daytime sleepiness (HR 0.86; 95% CI 0.79–0.93) were significantly related to reduced BPH risk. Each one‐point increment of the healthy sleep score was related to a decreased BPH risk, with an adjusted HR of 0.90 (95% CI 0.89–0.92). The multivariable‐adjusted HR in men adopting five versus zero to one low‐risk sleep traits was 0.68 (95% CI 0.61–0.75) for BPH risk. Estimates of the PAF indicated that 9.1% (95% CI 5.8–12.5%) of BPH cases would be prevented if all individuals had adopted all five low‐risk sleep traits, assuming causality. Conclusions Our study indicates an association between a healthy sleep pattern and a lower risk of BPH, emphasizing the importance of adhering to such patterns for potentially reducing BPH risk. Geriatr Gerontol Int 2024; 24: 675–682 .

This study aims to develop machine learning (ML)-assisted models for analyzing datasets related to Gleason scores in prostate cancer, conducting statistical analyses on the datasets, and identifying meaningful features. We retrospectively collected data from 717 hormone-sensitive prostate cancer (HSPC) patients at Yunnan Cancer Hospital. Of these, data from 526 patients were used for modeling. Seven auxiliary models were established using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), Extreme gradient boosting tree (XGBoost), Adaptive Boosting (Adaboost), and artificial neural network (ANN) based on 21 clinical biochemical indicators and features. Evaluation metrics included accuracy (ACC), precision (PRE), specificity (SPE), sensitivity (SEN) or regression rate(Recall), and f1 score. Evaluation metrics for the models primarily included ACC, PRE, SPE, SEN or Recall, f1 score, and area under the curve(AUC). Evaluation metrics were visualized using confusion matrices and ROC curves. Among the ensemble learning methods, RF, XGBoost, and Adaboost performed the best. RF achieved a training dataset score of 0.769 (95% CI: 0.759—0.835) and a testing dataset score of 0.755 (95% CI: 0.660—0.760) (AUC: 0.786, 95%CI: 0.722—0.803), while XGBoost achieved a training dataset score of 0.755 (95% CI: 95%CI: 0.711—0.809) and a testing dataset score of 0.745 (95% CI: 0.660—0.764) (AUC: 0.777, 95% CI: 0.726—0.798). Adaboost scored 0.789 on the training dataset (95% CI: 0.782—0.857) and 0.774 on the testing dataset (95% CI: 0.651—0.774) (AUC: 0.799, 95% CI: 0.703—0.802). In terms of feature importance (FI) in ensemble learning, Bone metastases at first visit, prostatic volume, age, and T1-T2 have significant proportions in RF’s FI. fPSA, TPSA, and tumor burden have significant proportions in Adaboost’s FI, while f/TPSA, LDH, and testosterone have the highest proportions in XGBoost. Our findings indicate that ensemble learning methods demonstrate good performance in classifying HSPC patient data, with TNM staging and fPSA being important classification indicators. These discoveries provide valuable references for distinguishing different Gleason scores, facilitating more accurate patient assessments and personalized treatment plans.

BACKGROUND:Few models exist to predict mortality in cancer patients receiving immunotherapy. Our aim was to build a machine learning-based risk stratification model for predicting mortality in atezolizumab-treated cancer patients. METHODS:Data from 2538 patients in eight atezolizumab-treated cancer clinical trials across three cancer types (non-small-cell lung cancer, bladder transitional cell carcinoma, and renal cell carcinoma) were included. The whole cohort was randomly split into development and validation cohorts in a 7:3 ratio. Machine-learning algorithms (extreme gradient boosting, random forest, logistic regression with lasso regularization, support vector machine, and K-nearest neighbor) were applied to develop prediction models. Model performance was mainly assessed by area under the receiver operating characteristic curve (AUC) value, calibration plot, and decision curve analysis. The probability of death risk was then stratified. RESULTS:One thousand and three hundred and seventy-nine (54.33%) patients died. The random forest (RF) model was overall the best in terms of predictive performance, with the AUC of 0.844 (95% confidence interval [CI]: 0.826-0.862) in the development cohort and 0.786 (95% CI: 0.754-0.818) in the validation cohort for predicting mortality. Twelve baseline variables contributing to mortality prediction in the RF model were C-reactive protein, PD-L1 level, cancer type, prior liver metastasis, derived neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, hemoglobin, white blood cell count, number of metastatic sites, pulse rate, and Eastern Cooperative Oncology Group (ECOG) performance status. A total of 1782 (70.2%) patients were separated into the high-risk and 756 (29.8%) low-risk groups. Patients in the high-risk group were significantly more likely to die, experience disease progression, discontinue study, and discontinue treatment than patients in the low-risk group (all p values < 0.001). Risk groups were not associated with immune-related adverse events and grades 3-5 treatment-related adverse events (all p values > 0.05). CONCLUSION:RF model has good performance in mortality prediction and risk stratification for cancer patients receiving atezolizumab monotherapy.

BACKGROUND:Ghrelin (GHRL) is a polypeptide that can specifically bind to the growth hormone secretagogue receptor (GHSR). The expression of GHSR is significantly different in normal and prostate cancer (PC) tissues in humans. It is important to find an effective diagnostic method for the diagnosis and prognosis of invasive PC/neuroendocrine prostate cancer (NEPC). METHODS:GHRL and GHSR mRNA levels were determined by a quantitative real-time polymerase chain reaction in PC tissues. The expression of GHRL and GHSR proteins was assessed by Western blot assay and immunohistochemistry. A GHRL polypeptide probe was synthesized by standard solid-phase polypeptide synthesis, and labeled with Alexa Fluor 660. Confocal microscopy was used to capture fluorescence images. Living imaging analysis showed tumor areas of different invasiveness in mice models. RESULTS:The levels of GHRL and GHSR copy number amplification and mRNA expression were increased in invasive PC/NEPC, and the protein expression levels of GHRL and GHSR were similarly increased in NEPC. The GHRL polypeptide probe could effectively bind to GHSR. In PC3 cells, it was found that the GHRL probe specifically binds to GHSR on the cell membrane and accumulates in the cells through internalization after binding. Live imaging in mice models showed that there were different signal intensities in tumor areas with different invasiveness. CONCLUSION:GHSR and GHRL might be used in molecular imaging diagnosis for invasive PC/NEPC in the future.

Background Single agent of PD-1 or PD-L1 inhibitor has been explored recently for resectable patients before surgery. However, the effectiveness and safety of neoadjuvant PD-1 blockade combine with platinum-based doublet chemotherapy has not been fully investigated. Methods 21 patients with squamous cell lung cancer accepted neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were involved. 8 patients accepted two cycles of neoadjuvant platinum-based doublet chemotherapy combine with anti-PD-1 therapy, while 13 patients accepted two cycles of neoadjuvant platinum doublet chemotherapy. Besides baseline tumor staging, chest CT was repeated two to three weeks before surgery. Adverse events were monitored. Peripheral lymphocytes counting was tested during whole treatment. The residual viable tumor cells were counted after surgery to decide a major pathological response (MPR) rate. Selected specimen was sent for immunohistochemical, multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing. Results Comparing with neoadjuvant chemotherapy alone, combination with PD-1 blockade and chemotherapy increased the pathological complete response rate (37·5% Vs. 7·69%) and MPR rate (50% Vs. 38·46%). The pathological evaluation is not consistent with that of radiological evaluation. Although peripheral lymphocyte counting was influenced by neoadjuvant therapy, no unknown adverse effects were reported for all the patients. The tumor infiltrating lymphocytes were observed more in patients accepted PD-1 blockade, and seem infiltrated more in relative “non-responders”. No special pathological features associated with PD-1 blockade were found. Multiplexed immunofluorescence analyses revealed potential immune suppression status in the peritumoral spaces around the residual tumor cells. T-cell receptor DNA sequencing found although some amino acids were shared in primary tumor and lymph nodes in single patients, they are hardly shared among different patients. Conclusions Neoadjuvant chemotherapy combine with PD-1 blockade is safe and feasible for patients with potentially resectable squamous cell lung cancer, to improve the clinical and pathological outcome. Even with PD-1 blockade, the immune suppressive status around the residual tumor cells still exists. The squamous cell lung cancers, and corresponding immune responses are extremely highly individualized. The treatment needs to be designed accordingly. The combination strategy of traditional neoadjuvant chemotherapy with current anti-PD-1 inhibitor are still need further investigation.

Cadherin related family member 2 (CDHR2) belongs to the protocadherin family and is abundant in normal liver, kidney, and colon tissues, but weakly expressed in cancers arising from these tissues. In this study, we demonstrated that CDHR2 was highly expressed in para-cancer tissues of human hepatocellular carcinoma (HCC), but significantly downregulated or silenced in 85.7% (6/7) of HCC cell lines by both semi-quantitative PCR and western blot, and 79.1% (19/24) and 80.2% (89/111) of tumor tissues from patients with HCC by semi-quantitative PCR, and immunohistochemistry, respectively. Interestingly, CpG islands in the promoter of CDHR2 gene were hypermethylated in HCC cell lines and tissues compared with the para-cancer tissues by methylation-specific PCR analysis, leading to transcriptional repression and silencing of CDHR2 in HCC. In addition, CDHR2 overexpression by lentiviral vectors had suppressive effects on HCC cell growth and proliferation, as evidenced by prolonged cell doubling time and reduced colony-forming ability in vitro, as well as by decreased tumorigenicity in vivo. Mechanistically, CDHR2 overexpression resulted in AKT dephosphorylation along with downregulation of cyclooxygenase-2 (COX2), a downstream target of AKT. This effect was reversed by myristoylated AKT, a constitutively active form of AKT, suggesting an involvement of CDHR2-AKT-COX2 axis in the suppression of HCC growth. Taken together, our study identified CDHR2 as a novel tumor suppressor in HCC and provided a new therapeutic target for HCC.

Objective To analyze the safety and effectiveness of robot-assisted laparoscopic partial nephrectomy(RLPN) for cT2 renal tumors in international multi-centers.Methods This study was conducted to collect information on surgical procedures performed by RLPN and robot assisted laparoscopic radical nephrectomy (RRN) in nineteen international urological centers from January 2012 to December 2017.RLPN were performed in 159 patients (118 males and 41 females),with the average age of (59.3 ± 13.2) years,body mass index(BMI) of (28.7 ± 5.4)kg/m2,preoperative GFR of (77.3 ± 22.1) ml/min.RRN were performed in 219 patients,with the average age of (62.0 ± 12.9) years,BMI of (28.7 ±6.1) kg/m2,preoperative GFR of (71.4 ± 20.3) ml/min.There was no statistical difference between the two groups in gender and BMI.The age of the patients in RLPN group was younger than that in RRN group,and the preoperative GFR was better.The patient's baseline demographics,perioperative data,tumor pathology,oncologic outcomes,and renal function (GFR) were recorded.Results All 378 cases underwent successful surgery.The operation time of RLPN was 150 min(65-353 min),which was shorter than that of RRN [180 min(85-361 min),P ＜ 0.001].The intra-operative blood loss of RLPN was more than that of RRN [150 ml (40-3 000 ml) vs.100 ml (10-1 100 ml),P ＜ 0.001].The incidence of intra-operative complications were not statistically different between the two groups [5.7％ (9/159) vs.3.2％ (7/219),P =0.240].The incidence of postoperative complications was higher in the RLPN group than that in RRN group [19.5％ (31/159) vs.10.5％ (23/219),P =0.014],but there was no significant difference in the incidence of complications of grade 3 or above [4.4％ (7/159) vs.2.3％ (5/219),P =0.246].The recurrence-free survival rate of RLPN group was higher than that of RRN group [91.4％ (117/128) vs.81.9％ (167/204),P =0.013],and RLPN group was more conducive to renal function protection (P ＜ 0.001).Conclusions RLPN for cT2 tumors can obtain effective tumor control rate and better renal function preservation.It could be an acceptable alternative for surgical management of cT2 tumors.

Background:To analyze the effect of two different trocar layout methods, which include the midline and lateral transperitoneal approach, on the robotic-assisted partial nephrectomy (RAPN).Methods: Transperitoneal approach was used in all the cases.In the midline layout group, 12-mm camera port was placed 2 cm to navel, besides the rectus abdominis.An 8-mm robotic trocar was placed on the lateral margin of the rectus abdominis, 3 cm from the costal margin approximately.Another 8-mm robotic arm trocar was placed to the point that 5 cm away from anterior superior iliac spine.Insert the 12-mm assistant trocar next to the rectus abdominis and on the right side, 5-mm assistant trocar was planted in the central line of the lower abdomen.For the lateral transperitoneal approach, place the 12-mm Trocar located in the midpoint between the nephroid projection and navel.The 8-mm robot Trocar is placed on the side of the lens hole, with the distance greater than 3 cm.The other 8-mm robot trocar was suggested to be put in the place greater than 3 cm from the iliac crest.The 12-mm auxiliary Trocar is placed above the navel.A 5-mm auxiliary Trocar was placed in the midline of the xiphoid process.Results: In the midline layout group, 50 cases were

Recent studies have examined the impact of phosphodiesterase type 5 inhibitors (PDE5-Is) use on the risk of prostate cancer, and biochemical recurrence (BCR) in prostate cancer patients, but the results were inconsistent. A meta-analysis was conducted to assess the associations with all published studies. Databases (PubMed, Web of Science and MEDLINE) were retrieved to identify relevant studies which explored the impact of PDE5-Is use on the risk of prostate cancer, and BCR in prostate cancer patients. The summary results along with 95% confidence intervals (CIs) were calculated. Nine articles were eligible for the inclusion criteria. The pooled analysis showed that PDE5-Is use was not related to the increased risk of prostate cancer (odds ratio (OR), 0.71; 95% CI, 0.40-1.29). Moreover, PDE5-Is use was not linked to BCR risk in prostate cancer patients with erectile dysfunction (ED) following radical prostatectomy or radiation therapy (relative risk (RR), 1.09; 95% CI, 0.89-1.34). The heterogeneity test suggested moderate heterogeneity across studies. PDE5-Is use does not influence the risk of prostate cancer, and BCR in prostate cancer patients. More well-designed studies are warranted to confirm the findings of our analyses.

We report a new approach to create metal-binding site in a series of metal-organic frameworks (MOFs), where tetratopic carboxylate linker, 4',4'',4''',4''''-methanetetrayltetrabiphenyl-4-carboxylic acid, is partially replaced by a tritopic carboxylate linker, tris(4-carboxybiphenyl)amine, in combination with monotopic linkers, formic acid, trifluoroacetic acid, benzoic acid, isonicotinic acid, 4-chlorobenzoic acid, and 4-nitrobenzoic acid, respectively. The distance between these paired-up linkers can be precisely controlled, ranging from 5.4 to 10.8 Å, where a variety of metals, Mg2+ , Al3+ , Cr3+ , Mn2+ , Fe3+ , Co2+ , Ni2+ , Cu2+ , Zn2+ , Ag+ , Cd2+ and Pb2+ , can be placed in. The distribution of these metal-binding sites across a single crystal is visualized by 3D tomography of laser scanning confocal microscopy with a resolution of 10 nm. The binding affinity between the metal and its binding-site in MOF can be varied in a large range (observed binding constants, Kobs from 1.56×102 to 1.70×104  L mol-1 ), in aqueous solution. The fluorescence of these crystals can be used to detect biomarkers, such as cysteine, homocysteine and glutathione, with ultrahigh sensitivity and without the interference of urine, through the dissociation of metal ions from their binding sites.

Objective:To construct a CDHR2 conditional knockout mouse model, and to provide conditions for the study on biological function of CDHR2 gene.Methods:The conditional CDHR2 targeting vector was constructed and transfected into mouse embryonic stem (ES) cells by electroporation.The positive ES cells screened by G418 and GANC were microinjected into the blastocysts of C57BL/6J mice.The chimeric mice were obtained and then mated with Cre mice to obtain conditional CDHR2 knockout mice.The phenotype was analyzed by PCR and immunohistochemistry, respectively.Results:The conditional CDHR2 targeting vector was successfully constructed, with six positive clones of ES cells being obtained.The positive clones of ES cells were microinjected into blastocysts of C57BL/6J mice with 5 chimeric mice being obtained.The chimeric mice were mated with Flp mice, and 6 positive F1 generation mice without Neo gene were obtained.Finally, such mice were hybridized with Cre mice to obtain intestine-specific CDHR2 knockout mice.Immunohistochemistry assay showed that the CDHR2 gene in intestinal tracts of the positive mice was specifically knocked out.In contrast, the expression of CDHR2 in kidney tissue was not affected.Conclusions:The successful construction of intestine-specific CDHR2 knockout mice has laid the foundation for provides a basis for further functional study on CDHR2 gene.

The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

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.