BarlowTwins-CXR: enhancing chest X-ray abnormality localization in heterogeneous data with cross-domain self-supervised learning.

BACKGROUND: Chest X-ray imaging based abnormality localization, essential in diagnosing various diseases, faces significant clinical challenges due to complex interpretations and the growing workload of radiologists. While recent advances in deep learning offer promising solutions, there is still a critical issue of domain inconsistency in cross-domain transfer learning, which hampers the efficiency and accuracy of diagnostic processes. This study aims to address the domain inconsistency problem and improve autonomic abnormality localization performance of heterogeneous chest X-ray image analysis, particularly in detecting abnormalities, by developing a self-supervised learning strategy called "BarlwoTwins-CXR". METHODS: We utilized two publicly available datasets: the NIH Chest X-ray Dataset and the VinDr-CXR. The BarlowTwins-CXR approach was conducted in a two-stage training process. Initially, self-supervised pre-training was performed using an adjusted Barlow Twins algorithm on the NIH dataset with a Resnet50 backbone pre-trained on ImageNet. This was followed by supervised fine-tuning on the VinDr-CXR dataset using Faster R-CNN with Feature Pyramid Network (FPN). The study employed mean Average Precision (mAP) at an Intersection over Union (IoU) of 50% and Area Under the Curve (AUC) for performance evaluation. RESULTS: Our experiments showed a significant improvement in model performance with BarlowTwins-CXR. The approach achieved a 3% increase in mAP50 accuracy compared to traditional ImageNet pre-trained models. In addition, the Ablation CAM method revealed enhanced precision in localizing chest abnormalities. The study involved 112,120 images from the NIH dataset and 18,000 images from the VinDr-CXR dataset, indicating robust training and testing samples. CONCLUSION: BarlowTwins-CXR significantly enhances the efficiency and accuracy of chest X-ray image-based abnormality localization, outperforming traditional transfer learning methods and effectively overcoming domain inconsistency in cross-domain scenarios. Our experiment results demonstrate the potential of using self-supervised learning to improve the generalizability of models in medical settings with limited amounts of heterogeneous data. This approach can be instrumental in aiding radiologists, particularly in high-workload environments, offering a promising direction for future AI-driven healthcare solutions.

A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling.

N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, and translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated and positively correlated with poor survival of patients with wild-type p53-expressing prostate cancer (PCa). m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. We further showed that FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs. Therapeutic depletion of FTO-IT1 restored mRNA m6A level and expression of p53 target genes and inhibited PCa growth in mice. Our study identifies FTO-IT1 lncRNA as a bona fide suppressor of the m6A methyltransferase complex and p53 tumor suppression signaling and nominates FTO-IT1 as a potential therapeutic target of cancer.

SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition.

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.

FOXA1 overexpression suppresses interferon signaling and immune response in cancer.

Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.

A noncanonical AR addiction drives enzalutamide resistance in prostate cancer.

Resistance to next-generation anti-androgen enzalutamide (ENZ) constitutes a major challenge for the treatment of castration-resistant prostate cancer (CRPC). By performing genome-wide ChIP-seq profiling in ENZ-resistant CRPC cells we identify a set of androgen receptor (AR) binding sites with increased AR binding intensity (ARBS-gained). While ARBS-gained loci lack the canonical androgen response elements (ARE) and pioneer factor FOXA1 binding motifs, they are highly enriched with CpG islands and the binding sites of unmethylated CpG dinucleotide-binding protein CXXC5 and the partner TET2. RNA-seq analysis reveals that both CXXC5 and its regulated genes including ID1 are upregulated in ENZ-resistant cell lines and these results are further confirmed in patient-derived xenografts (PDXs) and patient specimens. Consistent with the finding that ARBS-gained loci are highly enriched with H3K27ac modification, ENZ-resistant PCa cells, organoids, xenografts and PDXs are hyper-sensitive to NEO2734, a dual inhibitor of BET and CBP/p300 proteins. These results not only reveal a noncanonical AR function in acquisition of ENZ resistance, but also posit a treatment strategy to target this vulnerability in ENZ-resistant CRPC.

A 5-lncRNA Signature Associated with Smoking Predicts the Overall Survival of Patients with Muscle-Invasive Bladder Cancer.

Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a P value < 0.05 through the limma package. Subsequently, a comparison between patients with no tobacco smoke exposure for <15 years and patients who had been exposed to tobacco smoke for >15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation.

ZMYND8 preferentially binds phosphorylated EZH2 to promote a PRC2-dependent to -independent function switch in hypoxia-inducible factor-activated cancer.

Both gene repressor (Polycomb-dependent) and activator (Polycomb-independent) functions of the Polycomb protein enhancer of zeste homolog 2 (EZH2) are implicated in cancer progression. EZH2 protein can be phosphorylated at various residues, such as threonine 487 (T487), by CDK1 kinase, and such phosphorylation acts as a Polycomb repressive complex 2 (PRC2) suppression "code" to mediate the gene repressor-to-activator switch of EZH2 functions. Here we demonstrate that the histone reader protein ZMYND8 is overexpressed in human clear cell renal cell carcinoma (ccRCC). ZMYND8 binds to EZH2, and their interaction is largely enhanced by CDK1 phosphorylation of EZH2 at T487. ZMYND8 depletion not only enhances Polycomb-dependent function of EZH2 in hypoxia-exposed breast cancer cells or von Hippel-Lindau (VHL)-deficient ccRCC cells, but also suppresses the FOXM1 transcription program. We further show that ZMYND8 is required for EZH2-FOXM1 interaction and is important for FOXM1-dependent matrix metalloproteinase (MMP) gene expression and EZH2-mediated migration and invasion of VHL-deficient ccRCC cells. Our results identify a previously uncharacterized role of the chromatin reader ZMYND8 in recognizing the PRC2-inhibitory phosphorylation "code" essential for the Polycomb-dependent to -independent switch of EZH2 functions. They also reveal an oncogenic pathway driving cell migration and invasion in hypoxia-inducible factor-activated (hypoxia or VHL-deficient) cancer.

HDAC5 Loss Impairs RB Repression of Pro-Oncogenic Genes and Confers CDK4/6 Inhibitor Resistance in Cancer.

The tumor-suppressor protein RB acts as a transcription repressor via interaction of its pocket domain with an LXCXE motif in histone deacetylase (HDAC) proteins such as HDAC1. Here, we demonstrate that HDAC5 deficient for the LXCXE motif interacts with both RB-N (via an FXXXV motif) and RB-C segments, and such interactions are diminished by phosphorylation of RB serine-249/threonine-252 and threonine-821. HDAC5 was frequently downregulated or deleted in human cancers such as prostate cancer. Loss of HDAC5 increased histone H3 lysine 27 acetylation (H3K27-ac) and circumvented RB-mediated repression of cell-cycle-related pro-oncogenic genes. HDAC5 loss also conferred resistance to CDK4/6 inhibitors such as palbociclib in prostate and breast cancer cells in vitro and prostate tumors in vivo, but this effect was overcome by the BET-CBP/p300 dual inhibitor NEO2734. Our findings reveal an unknown role of HDAC5 in RB-mediated histone deacetylation and gene repression and define a new mechanism modulating CDK4/6 inhibitor therapeutic sensitivity in cancer cells. SIGNIFICANCE: This study defines a previously uncharacterized role of HDAC5 in tumor suppression and provides a viable strategy to overcome CDK4/6 inhibitor resistance in HDAC5-deficent cancer.

GPM6B Inhibit PCa Proliferation by Blocking Prostate Cancer Cell Serotonin Absorptive Capacity.

Prostate cancer is currently one of the most common fatal tumor types in men. Although multiple treatments can alleviate some cases, advanced prostate cancer, especially CRPC, still has a very poor prognosis. Therefore, early detection and diagnosis of prostate cancer have a very important role in the prognosis of patients. Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family. GPM6B has been proved and can be used as a biomarker for gynecological malignancies and breast carcinoma. However, there are no studies that explored the functions of GPM6B in PCa. We explored differentially expressed genes in prostate cancer by analyzing TCGA data and found GPM6B downregulated in PCa tissues compared to that in normal prostate tissues. The GPM6B expression in PCa patient's tumor tissues was significantly related to clinical stage, T classification, lymph node metastasis, and distant metastasis, but not significantly related to age and Gleason score. Also, patients with highGPM6B expression had a better prognosis. The overexpression of GPM6B in prostate cancer cells could inhibit cell proliferation. Serotonin treatment could enhance the proliferation of PCa cell lines; moreover, fluoxetine could reverse this result. In conclusion, we identified GPM6B as a tumor suppressor in PCa. In mechanism, it can regulate the uptaking of serotonin and inhibit the growth of prostate cancer. These results suggested the potential function of GPM6B as a diagnostic marker of PCa and provided clues for the development of new treatment targets for PCa.

Poliovirus receptor CD155 is up-regulated in muscle-invasive bladder cancer and predicts poor prognosis.

OBJECTIVE: To investigate the expression pattern of CD155 and evaluate the prognostic value of CD155 in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Immunohistochemical staining of CD155 and survival analysis were conducted on 228 nonmetastatic MIBC patients underwent radical cystectomy in cohorts from Fudan University Shanghai Cancer Center and Zhongshan Hospital. Association of CD155 gene expression with tumor stage and survival were analyzed in TCGA and GSE13507 dataset. RESULTS: CD155 was significantly up-regulated in MIBC compared to matched normal urothelium and majorly stained on the membrane of tumor cells. In Fudan MIBC cohort, CD155 high expression was significantly correlated with shorter recurrence-free survival (HR = 2.13, P < 0.001) and overall survival (HR = 2.49, P < 0.001). CD155 expression, T stage, and lymph node status were independent factors for predicting survival in multivariate analysis. In TCGA dataset, CD155 high expression was independently associated with shorter overall survival (HR = 1.74, P = 0.001) beyond age, T stage, and lymph node status. Further, explorative analysis in Fudan MIBC cohort showed that adjuvant chemotherapy was associated with longer recurrence-free survival and overall survival in stage III and IV disease with CD155-high tumors. CONCLUSIONS: These findings suggest that CD155 is a robust prognostic factor and may help predict the benefit of adjuvant chemotherapy in MIBC.

Prognostic implication and functional annotations of Rad50 expression in patients with prostate cancer.

Increasing evidence has shown that Rad50, a protein involved in the DNA damage repair process, significantly correlated with tumor prognosis. This study focused on Rad50 expression in tumor samples and its prognostic value for patients with prostate cancer (PCa). In this study, significantly elevated Rad50 expression in PCa tissues compared to normal tissues (P < .01). Five independent Oncomine databases validated significant differential expression of Rad50 (P < .001). Hence, 80 patients with PCa from Fudan University Shanghai Cancer Center (FUSCC) and 351 patients with PCa with available protein expression data from The Cancer Genome Atlas (TCGA) were included to investigate the survival benefit. Univariate and multivariate Cox regression analyses were performed to investigate the significance of clinicopathological factors on disease-free survival (DFS) and overall survival (OS). Kaplan-Meier analysis indicated that elevated Rad50 protein expression levels significantly correlated with unfavorable DFS (P = .005) in the FUSCC cohort and poorer OS (P = .04) in TCGA cohort. Furthermore, coregulation analysis of proteins indicated that 76 coregulated proteins were associated with Rad50, while 11 most highly involved hub proteins, including Rad50, MRE11A, DUT, POLR3A, MCM3AP, RECQL, PNPT1, RANBP3, DDX1, SNRPB, and UGN, were significantly coregulated in the protein-protein interaction network. Functional enrichment analysis consecutively indicated significant functions and signaling pathways including DNA replication, spliceosome, DNA geometric change, homologous recombination, and G2M checkpoint. This study first reveals that elevated Rad50 expression is significantly associated with aggressive progression and poor survival for patients with PCa. Together, these data suggest that Rad50 may act as an oncoprotein, guide the molecular diagnosis, and may shed light on novel individual therapeutic strategies for progressive PCa patients.

circLPAR1 is a novel biomarker of prognosis for muscle-invasive bladder cancer with invasion and metastasis by miR-762.

Circular RNAs (circRNAs) are a specific form of non-coding RNAs, that serve a pivotal role in the development of human diseases, including Alzheimer's disease and cancer; however, only a few are known with respect to cancer. The present study identified a novel circRNA, circ lysophosphatidic acid receptor 1 (LPAR1) (hsa_circ_0087960), derived from two exons 226 base pairs in length, in muscle-invasive bladder cancer (MIBC) tissues. circLPAR1 was identified to be lowly expressed in MIBC tissues in a cohort of 125 cases, and predicted a poor disease-specific survival time, compared with patients with high circLPAR1 expression (52.4 vs. 56.0 months; P=0.001) by univariate and multivariate Cox regression analyses. Matrigel and wound healing assays also demonstrated that the invasion of 5637 and T24 bladder cancer cells were significantly enhanced following the knockdown of circLPAR1 by small interfering RNA (si-circLPAR1-1 in T24 cell line, P=0.01; si-circLPAR1-2 in 5637 cell line, P=0.003; si-circLPAR1-2 in T24 cell line, P=0.002; si-circLPAR1-2 in 5637 cell line, P=0.006). The bioinformatics analysis indicated that circLPAR1 may harbor specific microRNAs (miRNAs) according to the miRNAs seed sequence matching. A luciferase reporter assay revealed that miR-762 can inhibit the activity of the transfected luciferase gene when inserted in a circLPAR1 wild-type fragment, and this inhibition could be alleviated when the luciferase gene was inserted in a circLPAR1 fragment with the mutated miR-762 target site. In conclusion, the circLPAR1 may function as a potential novel and stable biomarker for the prognosis of MIBC and may be associated with the invasion and metastasis by miR-762.

Extracellular Vesicles Long RNA Sequencing Reveals Abundant mRNA, circRNA, and lncRNA in Human Blood as Potential Biomarkers for Cancer Diagnosis.

BACKGROUND: Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS: We presented an optimized strategy for exLR sequencing (exLR-seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types), and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS: More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR-seq sample from 1-2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) = 0.9527; 95% CI, 0.9170-0.9883], validation cohort (AUC = 0.9825; 95% CI, 0.9606-1), and testing cohort (AUC = 0.9627; 95% CI, 0.9263-0.9991). CONCLUSIONS: In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.

Incorporating non-biological factors into the TNM staging system for better prognostication and decision-making in testicular cancer.

BACKGROUND: We combined county-level socioeconomic status (SES), marital status and insurance status to introduce NBF-stage, which were further incorporated into the American Joint Committee on Cancer (AJCC) TNM staging system to generate an integrated staging system for better prognostication and decision-making for testicular cancer patients. METHODS: 15,324 eligible patients diagnosed with primary testicular cancer between January 1, 2007 and December 31, 2015 were strictly selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent survival predictors were determined based on Cox proportional hazards model. The Kaplan-Meier survival curves were conducted to describe the difference in predicting survival probability and the Multivariate Cox proportion hazard regression analyses were established to compare the cancer-specific survival (CSS) and overall survival (OS) difference among NBF stages or NBF-TNM subgroups. RESULTS: County-level SES, marital status and insurance status were independent prognostic non-biological factors (NBFs) in our study (P < 0.05). NBF-stage (combination of SES, marital status, and insurance status) was also an independent survival predictor in TC (P < 0.05). NBF1 patients had 167% increased risk of cancer-specific mortality (CSM) as compared to NBF0 patients in testicular cancer (P < 0.01). And NBF0 patients all had a better CSS as compared to NBF1 patients of the same TNM stage both in seminoma and non-seminomatous germ cell tumor (P < 0.05). CONCLUSIONS: Incorporation of NBFs into AJCC TNM staging system in testicular cancer would potentially impact treatment decisions where treatments would not be rendered for a typically curable cancer with multi-modal therapy.

Identification and validation of an 18-gene signature highly-predictive of bladder cancer metastasis.

We found two deviant groups that were unpredictable with clinical models predicting bladder cancer metastasis. The group G consists of patients at high risk of pN+ , but they have pN0. The group P consists of patients at low risk of pN+ , but they have pN+ . We aimed to determine the genetic differences between these two groups. 1603 patients from SEER database were enrolled to build a multivariate model. This model was applied to patients from the TCGA database to distinguish groups G and P. Differentially expressed genes between the two groups were identified. RT-qPCR was used to validate the results in a cohort from FUSCC. Two deviant groups were identified both in the SEER population and the TCGA population. Expression of 183 genes was significantly different between the two groups. 18 genes achieved significant statistical power in predicting lymph node metastasis excluding these two deviant groups. The 18-gene signature outperformed 3 other bladder cancer lymph node prediction tools in 2 external GEO datasets. RT-qPCR results of our own cohort identified NECTIN2 (P = 0.036) as the only gene that could predict metastasis. Our study showed a novel gene screening method and proposed an 18-gene signature highly predictive of bladder cancer metastasis.

Doubly Caged Linker for AND-Type Fluorogenic Construction of Protein/Antibody Bioconjugates and In Situ Quantification.

In situ quantification of the conjugation efficiency of azide-terminated synthetic polymers/imaging probes and thiol-functionalized antibodies/proteins/peptides was enabled by a doubly caged profluorescent and heterodifunctional core molecule C1 as a self-sorting bridging unit. Orthogonal dual "click" coupling of C1 with azide- and thiol-functionalized precursors led to highly fluorescent bioconjugates, whereas single-click products remained essentially nonfluorescent. Integration with FRET processes was also possible. For the construction of antibody-probe conjugates from an anti-carcinoembryonic antigen and a quinone-caged profluorescent naphthalimide derivative, the dual "click" coupling process with C1 was monitored on the basis of the emission turn-on of C1, whereas prominent changes in FRET ratios occurred for antibody-imaging-probe conjugates when specifically triggered by quinone oxidoreductase (NQO1), which is overexpressed in various types of cancer cells.

NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer.

BACKGROUND: Nuclear receptors (NRs) are a class of transcription factors that regulate many cellular functions through manipulation of gene expression and also play important roles in tumorigenesis, proliferation, progression and prognosis in various kinds of cancers according to recent studies. This work aimed to determine the predictive ability of NRs in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: A total of 308 MIBC patients with complete clinicopathological and RNASeq data from The Cancer Genome Atlas (TCGA) cohort were collected for filtration. Genes showed clear correlations with overall survival (OS) and recurrence free survival (RFS) were further validated in 123 MIBC patients recruited consecutively from 2008 to 2012 in Fudan University Shanghai Cancer Center (FUSCC) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. RESULTS: In TCGA cohort, we found that high NR1H3 (HR=0.779, 95% CI: 0.634 - 0.957), NR2C1 (HR=0.673, 95% CI: 0.458 - 0.989) and NR2F6 (HR=0.750, 95% CI: 0.574 - 0.980) expressions were independent factors of favorable OS, while only low NR1H3 (log-rank test, P=0.0076) and NR2F6 (log-rank test, P=0.0395) expressions had the ability to predict poor prognosis for RFS. Further, in FUSCC validating cohort, we confirmed that low NR1H3 expression level was independent factor of poor OS (HR=1.295, 95% CI: 1.064 - 1.576) and it had the ability to predict poor RFS (log-rank test, P=0.0059). CONCLUSIONS: Low NR1H3 expression level is an independent prognostic factor of poor OS, and can also predict worse RFS in MIBC patients. Our "TCGA filtrating and local database validating" model can help reveal more prognostic biomarkers and cast a new light in understanding certain gene function in MIBC.