Stimulator of interferon genes mediated immune senescence reveals the immune microenvironment and prognostic characteristics of bladder cancer.

Background: Studies have shown that the stimulator of interferon genes (STING) is critical in tumorigenesis, and development. This study aimed to investigate the immune profile and prognostic significance of STING-mediated immune senescence in bladder cancer (BLCA). Methods: We identified differential genes between tumor and normal tissue based on the Cancer Genome Atlas database, and used consensus clustering to identify BLCA subtypes. The genes most associated with overall survival were screened by further analysis and used to construct risk models. Then, comparing the immune microenvironment, tumor mutational load (TMB), and microsatellite instability (MSI) scores between different risk groups. Eventually, a nomogram was constructed based on clinical information and risk scores. The model was validated using receiver operating curves (ROC) and calibration plots. Results: We identified 160 differential genes, including 13 genes most associated with prognosis. Three subtypes of bladder cancer with different clinical and immunological features were identified. Immunotherapy was more likely to benefit the low-risk group, which had higher TMB and MSI scores. The nomogram was found to be highly predictive based on ROC analysis and calibration plots. Conclusion: The risk model and nomogram not only predict the prognosis of BLCA patients but also can guide the treatment.

ß-Lapachone, an NQO1 bioactivatable drug, prevents lung tumorigenesis in mice.

Lung cancer is one of the most lethal cancers with high incidence worldwide. The prevention of lung cancer is of great significance to reducing the social harm caused by this disease. An in-depth understanding of the molecular changes underlying precancerous lesions is essential for the targeted chemoprevention against lung cancer. Here, we discovered an increased NQO1 level over time within pulmonary premalignant lesions in both the KrasG12D-driven and nicotine-derived nitrosamine ketone (NNK)-induced mouse models of lung cancer, as well as in KrasG12D-driven and NNK-induced malignant transformed human bronchial epithelial cells (BEAS-2B and 16HBE). This suggests a potential correlation between the NQO1 expression and lung carcinogenesis. Based on this finding, we utilized ß-Lapachone (ß-Lap), an NQO1 bioactivatable drug, to suppress lung tumorigenesis. In this study, the efficacy and safety of low-dose ß-Lap were demonstrated in preventing lung tumorigenesis in vivo. In conclusion, our study suggests that long-term consumption of low-dose ß-Lap could potentially be an effective therapeutic strategy for the prevention of lung premalignant lesions. However, further studies and clinical trials are necessary to validate our findings, determine the safety of long-term ß-Lap usage in humans, and promote the use of ß-Lap in high-risk populations.

Bubble-like lucency in pulmonary ground glass nodules on computed tomography: a specific pattern of air-containing space for diagnosing neoplastic lesions.

PURPOSE: To investigate the computed tomography (CT) characteristics of air-containing space and its specific patterns in neoplastic and non-neoplastic ground glass nodules (GGNs) for clarifying their significance in differential diagnosis. MATERIALS AND METHODS: From January 2015 to October 2022, 1328 patients with 1,350 neoplastic GGNs and 462 patients with 465 non-neoplastic GGNs were retrospectively enrolled. Their clinical and CT data were analyzed and compared with emphasis on revealing the differences of air-containing space and its specific patterns (air bronchogram and bubble-like lucency [BLL]) between neoplastic and non-neoplastic GGNs and their significance in differentiating them. RESULTS: Compared with patients with non-neoplastic GGNs, female was more common (P < 0.001) and lesions were larger (P < 0.001) in those with neoplastic ones. Air bronchogram (30.1% vs. 17.2%), and BLL (13.0% vs. 2.6%) were all more frequent in neoplastic GGNs than in non-neoplastic ones (each P < 0.001), and the BLL had the highest specificity (93.6%) in differentiation. Among neoplastic GGNs, the BLL was more frequently detected in the larger (14.9 ± 6.0 mm vs. 11.4 ± 4.9 mm, P < 0.001) and part-solid (15.3% vs. 10.7%, P = 0.011) ones, and its incidence significantly increased along with the invasiveness (9.5-18.0%, P = 0.001), whereas no significant correlation was observed between the occurrence of BLL and lesion size, attenuation, or invasiveness. CONCLUSION: The air containing space and its specific patterns are of great value in differentiating GGNs, while BLL is a more specific and independent sign of neoplasms.

Investigation of temperature effects on wide steel box girder of suspension bridge based on long-term monitoring data.

The time-varying temperature distributions on bridge structures may remarkably change structural performance, which may result in differential strain/stress responses on structural members compared with the design conditions. Therefore, it is crucial to have a comprehensive understanding of temperature distributions and its effects on bridges. In this study, taking advantage of structural health monitoring technology, 1-year field monitoring data collected from a long-span suspension bridge were used to investigate the temperature distributions and their effects on the steel box girder. Specifically, the distributions and probability statistics of temperatures on the top and bottom plates were firstly analyzed. Based on which, the transverse and vertical temperature differences on the box girder were further examined, moreover, the representative values of temperature differences for various return periods were calculated by exceedance probability method. At end, a temperature prediction method was proposed to simulated the temperature field distributions during bridge life cycle, to provide substantial temperature data for estimating future operation condition. The results of this study were beneficial to structural evaluation of in-service bridges to ensure their serviceability and integrity in the life cycle.

The role of iron-rich hydrosaline liquids in the formation of Kiruna-type iron oxide-apatite deposits.

Kiruna-type iron oxide-apatite (IOA) deposits, an important source of iron, show close associations with andesitic subvolcanic intrusions. However, the processes of ore formation and the mechanism controlling iron concentration remain uncertain. Here, we report the widespread presence of high-temperature (>800°C) water-poor multisolid hydrosaline liquid inclusions in pre- and syn-ore minerals from IOA deposits of eastern China. These inclusions consistently homogenize to a liquid phase by vapor disappearance and mostly contain 3 to 10 wt % Fe, signifying a substantial capacity for iron transportation by such hydrosaline liquids. We propose that the hydrosaline liquids were likely immiscible from the dioritic magmas with high Cl/H2O in subvolcanic settings. Subsequent reaction with host rocks and/or decompression and cooling of the hydrosaline liquids is deemed responsible for the simultaneous formation of high-temperature alteration and magnetite ores, thereby providing important insights into the distinctive characteristics of IOA deposits in shallow magmatic-hydrothermal systems.

Pan-cancer analyses reveal genomics and clinical outcome association of the fatty acid oxidation regulators in cancer.

Background: Fatty acid oxidation (FAO) is considered to play a vital part in tumor metabolic reprogramming. But the comprehensive description of FAO dysregulation in tumors has not been unknown. Methods: We obtained FAO genes, RNA-seq data and clinical information from the Msigdb, TCGA and GTEx databases. We assessed their prognosis value using univariate cox analysis, survival analysis and Kaplan-Meier curve. We determined the function of FAO genes using gene set variation analysis. The correlation analysis was calculated by corrplot R package. Immunotherapy response was assessed through TIDE scores. The protein expression levels of FAO genes were validated using immunohistochemistry (IHC). Results: The FAO scores were highest in COAD but lowest in PCPG. FAO scores were significantly associated with the prognosis of some cancers in OS, DSS, DFI and PFI. Besides, gene set variation analysis identified that FAO scores were related to immune-related pathways, and immune infiltration analysis showed FAO scores were positively related to cancer-associated fibroblasts and various immune-related genes. TIDE scores were significantly decreased in ACC, CHOL, ESCA, GBM, LAML, SARC, SKCM and THCA compared with normal samples, while it was significantly increased in BLCA, LUAD, LUSC, PCPG, PRAD and STAD. Besides, most FAO genes were downregulated in pan-cancer compared with normal samples. Moreover, we found copy number variation (CNV) of FAO genes played a positive role in their mRNA expression, while methylation was negative. We determined FAO genes were closely related to some drugs in pan-cancer. Conclusions: FAO score is a novel and promising factor for predicting outcomes.

O-GlycoIsoQuant: A Novel O-Glycome Quantitative Approach through Superbase Release and Isotopic Girard's P Labeling.

Quantitative glycosylation analysis serves as an effective tool for detecting changes in glycosylation patterns in cancer and various diseases. However, compared with N-glycans, O-glycans present challenges in both qualitative and quantitative mass spectrometry analysis due to their low abundance, ease of peeling, lack of a universal enzyme, and difficult accessibility. To address this challenge, we developed O-GlycoIsoQuant, a novel O-glycome quantitative approach utilizing superbase release and isotopic Girard's P labeling. This method facilitates rapid and efficient nonreducing ß-elimination to dissociate O-glycans from proteins using the organic superbase, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), combined with light and heavy isotopic Girard's reagent P (GP) labeling for relative quantification of O-glycans by mass spectrometry. Employing this method, labeled O-glycans exhibit a double peak with a mass difference of 5 Da, suitable for stable relative quantification. The O-GlycoIsoQuant method is characterized by its high labeling efficiency, excellent reproducibility (CV < 20%), and good linearity (R2 > 0.99), across a dynamic range spanning a 100-fold range. This method was applied to various complex sample types, including human serum, porcine spermatozoa, human saliva, and urinary extracellular vesicles, detecting 33, 39, 49, and 37 O-glycans, respectively, thereby demonstrating its broad applicability.

Dexamethasone inhibits androgen receptor-negative prostate cancer cell proliferation via the GR-FOXO3a-GAS5 axis.

Background: Studies have shown that glucocorticoid receptor (GR) has inconsistent effects on the proliferation of prostate cancer cells, we found dexamethasone inhibited the proliferation of androgen receptor-negative prostate cancer cells, but the underlying mechanisms remain to be illustrated. Methods: GR expression and its prognosis role were analyzed based on the TCGA dataset. Bioinformatic analysis was performed to identify the candidate of GR downstream, which includes FOXO3a. After overexpressing FOXO3a in PC-3 cells, cell counting kit-8 (CCK-8) and migration assays were performed to evaluate cell proliferation and migration ability. Regulation of FOXO3a on GAS5 was also analyzed by JASPAR and PCR. Results: GR had low expression in prostate cancer and predicted poor prognosis. FOXO3a was identified as the downstream of GR to inhibit the proliferation of prostate cancer cells. Moreover, FOXO3a directly induces GAS5 expression, forming the GR-FOXO3a-GAS5 signaling pathway. Conclusion: Our study showed that GR played a role as a tumor suppressor gene in androgen receptor-negative prostate cancer cells via the GR-FOXO3a-GAS5 axis. Our results suggested patients with prostate cancer should be classified and develop a treatment plan according to the expression of AR and GR.

Identification and validation of shared gene signature of kidney renal clear cell carcinoma and COVID-19.

Background: COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated. Methods: We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases. Results: We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan. Conclusion: This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.

FATP2 activates PI3K/Akt/mTOR pathway by inhibiting ATF3 and promotes the occurrence and development of bladder cancer.

Bladder cancer (BLCA) is ranked among the main causes of mortality in male cancer patients, and research into targeted therapies guided by its genomics and molecular biology has been a prominent focus in BLCA studies. Fatty acid transporter protein 2 (FATP2), a member of the FATPs family,is a key contributor to the progression of cancers such as hepatocellular carcinomas and melanomas.However,its role in BLCA remains poorly understand. This study delved into the function of FATP2 in BLCA through a succession of experiments in vivo and in vitro, employing techniques as quantitative real-time polymerase chain reaction (qRT-PCR), RNA sequencing, transwell assays, immunofluorescence, western blot,and others to dissect its mechanistic actions. The findings revealed that an oncogenic function is executed by FATP2 in bladder cancer, significantly impacting the proliferation and migration capabilities, thereby affecting the prognosis of BLCA patients. Furthermore, A suppression that relies on both time and concentration of BLCA proliferation and migration, trigger of apoptosis, and blockage of the cell cycle at the G2/M phase were observed when the inhibitor of FATP2, Lipofermata, was applied. It was unveiled through subsequent investigations that ATF3 expression is indirectly promoted by Lipofermata through the inhibition of FATP2, ultimately inhibiting the signal transduction of the PI3K/Akt/mTOR pathway. This effect was also responsible for the inhibitory impact on BLCA proliferation. Therefore, FATP2 emerges as an auspicious and emerging molecular target with potential applications in precision therapy in BLCA.

Serotonin receptor HTR2B facilitates colorectal cancer metastasis via CREB1-ZEB1 axis mediated epithelial-mesenchymal transition.

A number of neurotransmitters have been detected in tumor microenvironment and proved to modulate cancer oncogenesis and progression. We previously found that biosynthesis and secretion of neurotransmitter 5-hydroxytryptamine (5-HT) was elevated in colorectal cancer (CRC) cells. In this study, we discovered that the HTR2B receptor of 5-HT was highly expressed in CRC tumor tissues, which was further identified as a strong risk factor for CRC prognostic outcomes. Both pharmacological blocking and genetic knocking down HTR2B impaired migration of CRC cell, as well as the epithelial-mesenchymal transition (EMT) process. Mechanistically, HTR2B signaling induced ribosomal protein S6 kinase B1 (S6K1) activation via Akt/mTOR pathway, which triggered cAMP responsive element binding protein 1 (CREB1) phosphorylation (Ser 133) and translocation into the nucleus, then the phosphorylated CREB1 acts as an activator for ZEB1 transcription after binding to CREB1 half-site (GTCA) at ZEB1 promoter. As a key regulator of EMT, ZEB1 therefore enhances migration and EMT process in CRC cells. We also found that HTR2B specific antagonist (RS127445) treatment significantly ameliorated metastasis and reversed EMT process in both HCT116 cell tail-vein-injected pulmonary metastasis and CT26 cell intrasplenic-injected hepatic metastasis mouse models. Implications: These findings uncover a novel regulatory role of HTR2B signaling on CRC metastasis, which provide experimental evidences for potential HTR2B-targeted anti-CRC metastasis therapy.

The outcome and predictive model of allogeneic hematopoietic stem cell transplantation among elderly patients with severe aplastic anemia from the Chinese Blood and Marrow Transplant Registry Group.

Not available.

Preliminary study on the role of the CSMD2 gene in bladder cancer.

Background: CSMD2 has been reported as a potential prognostic factor in several cancers. However, whether CSMD2 affects bladder cancer (BC) remains unclear. Methods: Public data were obtained from the TCGA (https://cancergenome.nih.gov) databases. CSMD2expression and its prognostic value were analyzed using bioinformatics methods. CSMD2 mRNA level in patients with BC and BC cell lines was evaluated via quantitative reverse transcriptase polymerase chain reaction. CSMD2 protein level in patients with BC was evaluated via immunohistochemistry. BC cell lines T24 and UMUC-3 were selected for loss-of-function assays targeting CSMD2. Cell viability was determined by CCK8 and clone formation experiments. Cell migration and invasion were evaluated using Transwell assays. Furthermore, the transcriptome of UMUC-3 with CSMD2 knockdown was sequenced to analyze potential signaling network pathways. Finally, the TIMER2.0 database was employed to identify the correlation between CSMD2 and immune cells in the tumor microenvironment. Results: CSMD2 expression was up-regulated in BC tissues compared to adjacent tissues. High CSMD2 expression was associated with poor survival and could serve as an independent predictor for survival in patients with BC. Furthermore, down-regulation of CSMD2 notably restrained the viability, migration, and invasion abilities of T24 and UMUC-3 cells. Moreover, transcriptomic sequencing after CSMD2 knockdown in UMUC-3 cells revealed its involvement in the regulation of the malignant phenotype in BC. Finally, public databases suggest a connection between CSMD2 and immune cell infiltration in BC. Conclusions: These findings suggest that CSMD2 may promote proliferation and tumorigenicity, and could represent a potential target for improving the prognosis of BC.

Targeting POLRMT by a first-in-class inhibitor IMT1 inhibits osteosarcoma cell growth in vitro and in vivo.

Osteosarcoma (OS) is a highly aggressive form of bone cancer that predominantly affects adolescents and young adults. In this study, we have undertaken an investigation into the potential anti-OS cell activity of IMT1 (inhibitor of mitochondrial transcription 1), a first-in-class inhibitor of RNA polymerase mitochondrial (POLRMT). IMT1 exhibited a profound inhibitory effect on cell survival, proliferation, cell cycle progression, and migration in primary and immortalized OS cells. Furthermore, this POLRMT inhibitor elicited apoptosis in the OS cells, without, however, inducing cytotoxicity in human osteoblasts or osteoblastic cells. IMT1 disrupted mitochondrial functions in OS cells, resulting in mitochondrial depolarization, oxidative injury, lipid peroxidation, and ATP reduction in OS cells. Silencing POLRMT using targeted shRNA closely mimicked the actions of IMT1 and exerted potent anti-OS cell activity. Importantly, IMT1's effectiveness was diminished in POLRMT-silenced OS cells. Subsequent investigations revealed that IMT1 suppressed the activation of the Akt-mammalian target of rapamycin (mTOR) cascade in OS cells. IMT1 treatment or POLRMT silencing in primary OS cells led to a significant reduction in Akt1-S6K-S6 phosphorylation. Conversely, it was enhanced upon POLRMT overexpression. The restoration of Akt-mTOR activation through the introduction of a constitutively active S473D mutant Akt1 (caAkt1) mitigated IMT1-induced cytotoxicity in OS cells. In vivo, oral administration of IMT1 robustly curtailed the growth of OS xenografts in nude mice. Furthermore, IMT1 suppressed POLRMT activity, impaired mitochondrial function, repressed Akt-mTOR activation, and induced apoptosis within xenograft tissues. Collectively, these findings underscore the potent growth-inhibitory effects attributed to IMT1 via targeted POLRMT inhibition. The utilization of this POLRMT inhibitor carries substantial therapeutic promise in the context of OS treatment.

Trends in suicide mortality among prostate cancer survivors in the United States, 1975-2019.

BACKGROUND: Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. METHOD: We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. RESULTS: 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09-1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17-2.51) in 1975-1979 to 0.99(0.89-1.1) in 2015-2019 (Ptrend < 0.001). PCa survivors with aged over 84 years, black and other races, registered in registrations (including Utah, New Mexico, and Hawaii) failed to observe a decrease in suicide mortality (Ptrend > 0.05). The cumulative suicide mortality during 1975-1994 was distinctly higher than in 1995-2019(P < 0.001). CONCLUSION: The trend in suicide mortality declined significantly from 1975 to 2019 among PCa survivors compared with the general male population in the United States. Notably, part of PCa survivors had no improvement in suicide mortality, and additional studies in the future were needed to explore it.

Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-Associated Macrophages and Their Precursor Cells in Tumor Progression.

Tumor-associated macrophages (TAMs) are key regulators in tumor progression, but the precise role of bone marrow-derived monocytes (Mons) as TAM precursors and their dynamic phenotypes regulated by the tumor microenvironment (TME) remain unclear. Here, we developed an optimized microproteomics workflow to analyze low-cell-number mouse myeloid cells. We sorted TAMs and their corresponding Mons (1 × 105 per sample) from individual melanoma mouse models at both the early and late stages. We established the protein expression profiles for these cells by mass spectrometry. Subsequently, we analyzed the dynamics phenotypes of TAMs and identified a characteristic protein expression profile characterized by upregulated cholesterol metabolism and downregulated immune responses during tumor progression. Moreover, we found the downregulation of both STAT5 and PYCARD expression not only in late-stage TAMs but also in late-stage Mons, indicating a loss of the ability to induce inflammatory responses prior to Mons infiltration into TME. Taken together, our study provides valuable insights into the progression-dependent transitions between TAMs and their precursor cells, as well as the cross-organ communications of tumor and bone marrow.

Causal relationship between prostate cancer and 12 types of cancers: multivariable and bidirectional Mendelian randomization analyses.

BACKGROUND: Previous observational studies have shown an association between certain cancers and the subsequent risk of prostate cancer (PCa). However, the causal relationship between these cancers and PCa is still unclear. This study aimed to investigate the causal relationship between 12 common cancers and the risk of PCa. METHODS: We employed genome-wide association studies (GWAS) to perform forward and reverse Mendelian randomization (MR) within two-sample frameworks. Furthermore, we conducted multivariable MR analyses to investigate the relationships between different types of cancer. In addition, multiple sensitivity analysis methods were employed to assess the robustness of our findings. RESULTS: Our univariable MR analysis showed that genetically predicted hematological cancer was associated with a reduced risk of PCa (OR: 0.911, 95% CI 0.89-0.922, P = 0.03). Furthermore, MR analysis demonstrates that genetically predicted occurrence of thyroid gland and endocrine gland cancer also raised the risk of PCa (all P < 0.05). Multivariable analysis showed that thyroid gland cancer exhibited a higher incidence of PCa (OR: 1.12, 95% CI: 1.08-1.16, P = 0.008). In the reverse MR analysis, we found no significant inverse causal associations between PCa and 12 types of cancers. CONCLUSION: In summary, this study provided insights into the causal relationships between various types of cancer and PCa. Hematological cancer was suggested to associate with a lower risk of PCa, while thyroid gland cancer and endocrine gland cancer might increase the risk. These findings contribute to the understanding of genetic factors related to PCa and its potential associations with other cancers.

CircFSCN1 induces tumor progression and triggers epithelial-mesenchymal transition in bladder cancer through augmentation of MDM2-mediated p53 silencing.

BACKGROUND: Compelling evidences indicated that circular RNA (circRNA) was a novel class of non-coding RNA that played critical and distinct roles in various human cancers. Their roles and underlying mechanisms, however, in bladder cancer (BC) remained largely unknown. METHODS: A novel circRNA derived from oncogene FSCN1, namely circFSCN1, was selected from a microarray analysis. The phenotypic alterations were assessed with functional experiments in vitro and in vivo. RNA immunoprecipitation, RNA pull-down, luciferase reporter assay, and rescue experiments were sequentially proceeded to clarify the interactions among circFSCN1, miR-145-5p, MDM2, and p53. RESULTS: We observed that the expression of circFSCN1 was elevated in BC cell lines and tissues. Next, we validated the fundamental properties of circFSCN1. In the meanwhile, we noticed that elevated circFSCN1 level, pathological T stage, and tumor grade were identified as independent factors associated with cancer-specific survivals of patients with BC，as determined by univariate and multivariable COX regression analyses. Phenotype studies demonstrated the promoting effects of circFSCN1 on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of BC cells. Mechanistically, we elucidated that circFSCN1, primarily localized in the cytoplasm, upregulated the expression of MDM2, a well-known inhibitor of p53, by directly binding to miR-145-5p. CONCLUSIONS: Elevated circFSCN1 induces tumor progression and EMT in BC via enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p. Targeting circFSCN1, a novel identified target, may be conducive in impeding BC progression and providing survival benefits for patients with BC.

Potential Role of Intrapulmonary Concomitant Lesions in Differentiating Non-Neoplastic and Neoplastic Ground Glass Nodules.

Purpose: To determine the value of intrapulmonary concomitant lesions in differentiating non-neoplastic and neoplastic ground-glass nodules (GGNs). Patients and Methods: From January 2014 to March 2022, 395 and 583 patients with confirmed non-neoplastic and neoplastic GGNs were retrospectively enrolled. Their clinical and chest CT data were evaluated. The CT features of target GGNs and intrapulmonary concomitant lesions in these two groups were analyzed and compared, and the role of intrapulmonary concomitant lesions in improving differentiation was evaluated. Results: The intrapulmonary concomitant lesions were more common in patients with non-neoplastic GGNs than in those with neoplastic ones (87.88% vs 82.18%, P = 0.015). Specifically, patients with non-neoplastic GGNs had a higher incidence of multiple solid nodules (SNs), patchy ground-glass opacity/consolidation, and fibrosis/calcification in any lung fields (each P < 0.05). Logistic regression analysis indicated that patients < 44 years old, diameter < 7.35 mm, irregular shape, and coarse margin or ill-defined boundary for target GGN, pleural thickening, and concomitant SNs in the same lobe and fibrosis or calcification in any lung field were independent indicators for predicting non-neoplastic GGNs. The AUC of the model for predicting non-neoplastic GGNs increased from 0.894 to 0.926 (sensitivity, 83.10%; specificity, 87.10%) after including the concomitant lesions in the patients' clinical characteristics and CT features of target GGNs (P < 0.0001). Conclusion: Besides the patients' clinical characteristics and CT features of target GGNs, the concomitant multiple SNs in the same lobe and fibrosis/calcification in any lung field should be considered in further differentiating non-neoplastic and neoplastic GGNs.