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BACKGROUND: To date, no study has systematically explored the potential role of serum metabolites and lipids in the diagnosis of small cell lung cancer (SCLC). Therefore, we aimed to conduct a case-cohort study that included 191 cases of SCLC, 91 patients with lung adenocarcinoma, 82 patients with squamous cell carcinoma, and 97 healthy controls. METHODS: Metabolomics and lipidomics were applied to analyze different metabolites and lipids in the serum of these patients. The SCLC diagnosis model (d-model) was constructed using an integrated machine learning technology and a training cohort (n = 323) and was validated in a testing cohort (n=138). RESULTS: Eight metabolites, including 1-mristoyl-sn-glycero-3-phosphocholine, 16b-hydroxyestradiol, 3-phosphoserine, cholesteryl sulfate, D-lyxose, dioctyl phthalate, DL-lactate and Leu-Phe, were successfully selected to distinguish SCLC from controls. The d-model was constructed based on these 8 metabolites and showed improved diagnostic performance for SCLC, with the area under curve (AUC) of 0.933 in the training cohort and 0.922 in the testing cohort. Importantly, the d-model still had an excellent diagnostic performance after adjusting the stage and related clinical variables and, combined with the progastrin-releasing peptide (ProGRP), showed the best diagnostic performance with 0.975 of AUC for limited-stage patients. CONCLUSION: This study is the first to analyze the difference between metabolomics and lipidomics and to construct a d-model to detect SCLC using integrated machine learning. This study may be of great significance for the screening and early diagnosis of SCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Biomarcadores Tumorais , LipídeosRESUMO
Endoplasmic reticulum-associated degradation (ERAD) is known to regulate plant responses to diverse stresses, yet its underlying molecular mechanisms and links to various stress signaling pathways are poorly understood. Here, we show that the ERAD component ubiquitin-conjugating enzyme UBC32 positively regulates drought tolerance in Arabidopsis thaliana by targeting the aquaporins PIP2;1 and PIP2;2 for degradation. Furthermore, we demonstrate that the RING-type ligase Rma1 acts together with UBC32 and that the E2 activity of UBC32 is essential for the ubiquitination of Rma1. This complex ubiquitinates a phosphorylated form of PIP2;1 at Lys276 to promote its degradation, thereby enhancing plant drought tolerance. Extending these molecular insights into crops, we show that overexpression of Arabidopsis UBC32 also improves drought tolerance in rice (Oryza sativa). Thus, beyond uncovering the molecular basis of an ERAD-regulated stress response, our study suggests multiple potential strategies for engineering crops with improved drought tolerance.
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Aquaporinas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Oryza/fisiologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Ácido Abscísico/metabolismo , Aquaporinas/genética , Proteínas de Arabidopsis/genética , Desidratação , Secas , Degradação Associada com o Retículo Endoplasmático , Lisina/metabolismo , Espectrometria de Massas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Oryza/genética , Oryza/crescimento & desenvolvimento , Fosforilação , Plantas Geneticamente Modificadas , Estabilidade Proteica , Enzimas de Conjugação de Ubiquitina/genética , UbiquitinaçãoRESUMO
BACKGROUND: There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC. METHODS: The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC. RESULTS: We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52-5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb). CONCLUSION: Our findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.
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Anticorpos Monoclonais Humanizados , Biomarcadores Tumorais , Neoplasias Pulmonares , Linfócitos , Neutrófilos , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Feminino , Linfócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Mutação , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócitos , Método Duplo-CegoRESUMO
Small-cell lung cancer (SCLC) is an exceptionally lethal malignancy characterized by extremely high alteration rates and tumor heterogeneity, which limits therapeutic options. In contrast to non-small-cell lung cancer that develops rapidly with precision oncology, SCLC still remains outside the realm of precision medicine. No recurrent and actionable mutations have been detected. Additionally, a paucity of substantive tumor specimens has made it even more difficult to classify SCLC subtypes based on genetic background. We therefore carried out whole-exome sequencing (WES) on the largest available Chinese SCLC cohort. For the first time, we partitioned SCLC patients into three clusters with different genomic alteration profiles and clinical features based on their mutational signatures. We showed that these clusters presented differences in intratumor heterogeneity and genome instability. Moreover, a wide existence of mutually exclusive gene alterations, typically within similar biological functions, was detected and suggested a high SCLC intertumoral heterogeneity. Particularly, Cluster 1 presented the greatest potential to benefit from immunotherapy, and Cluster 3 constituted recalcitrant SCLC, warranting biomarker-directed drug development and targeted therapies in clinical trials. Our study would provide an in-depth insight into the genome characteristics of the Chinese SCLC cohort, defining distinct molecular subtypes as well as subtype-specific therapies and biomarkers. We propose tailoring differentiated therapies for distinct molecular subgroups, centering on a personalized precision chemotherapy strategy combined with immunization or targeted therapy for patients with SCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Mutação , GenômicaRESUMO
BACKGROUND: Accumulating evidence has confirmed the role of snoRNAs in a variety of cancer, but rare in renal cell carcinoma (RCC). This study aims to clarify the role of snoRNAs in RCC tumorigenesis and their potential as novel tumor biomarkers. MATERIALS AND METHODS: The snoRNA expression matrix was obtained from the public TCGA and SNORic databases. SNORD15A, SNORD35B and SNORD60 were selected and validated by qPCR, then analyzed combined with related clinical factors using T-test and ROC curve. RESULTS: All three snoRNAs: SNORD15A, SNORD35B and SNORD60 were significantly upregulated in cancer tissues compared to adjacent tissues from TCGA or FFPE detection. These three snoRNAs were also increased in urinary sediment (US) of RCC as well as the early-stage RCC patients compared with the healthy controls. In addition, RNase stability experiments confirmed their stable existence in US. Meanwhile, the ROC curve shows that SNORD15A, SNORD35B and SNORD60 could effectively distinguish RCC (AUC = 0.7421) and early-stage RCC (AUC = 0.7465) from healthy individuals. CONCLUSION: SNORD15A, SNORD35B and SNORD60 were upregulated in tissues and US of RCC, serving as novel potential biomarkers for RCC diagnosis.
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BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients harboring neurotrophin receptor kinase (NTRK) family mutations remains obscure. METHODS: The Zehir cohort from cBioPortal was used to analyze the mutations (MT) frequency of NTRK family in patients with NSCLC, and their correlation with clinical characteristics and patient survival. The influence of NTRK MT on ICIs efficacy was evaluated in ICIs-treated patients from Samstein cohort and further validated by use of data from OAK/POPLAR cohort. RESULTS: In the Zehir cohort, a significant difference was observed in median overall survival (mOS) between patients with NTRK MT and wild-type (WT) (mOS: 18.97 vs. 21.27 months, HR = 1.34, 95%CI 1.00-1.78; log-rank P = 0.047). In Samstein cohort, the mOS of NTRK mutant patients receiving ICIs has improved compared to WT patients (mOS: 21.00 vs. 11.00 months, log-rank P = 0.103). Notably, in subgroup analysis, ICIs significantly prolonged mOS in patients with NTRK3 MT than in WT patients (mOS: not available vs. 11.00 months, HR = 0.36, 95%CI 0.16-0.81; log-rank P = 0.009). Identical mOS between NTRK MT and WT patients receiving ICIs treatment (mOS: 13.24 vs. 13.50 months, log-rank P = 0.775) was observed in OAK/POPLAR cohort. Moreover, a similar programmed death ligand 1 (PD-L1) expression, but higher tumor mutational burden (TMB), blood TMB (bTMB) and enriched anti-tumor immunity were observed in NTRK MT compared to WT (P < 0.05). CONCLUSION: Taking high TMB or bTMB into consideration, patients with NTRK mutant NSCLC could benefit from ICIs treatment.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Mutação , Biomarcadores Tumorais/genéticaRESUMO
Background: Uniparental disomy (UPD) is a well-known epigenomic anomaly characterized by the inheritance of both copies of a homologous pair of chromosomes (or part thereof) from the same parent. This genetic condition can have significant implications for prenatal diagnosis and management. Case Presentation: We present a case of a 29-year-old gravida 1 para 0 female who underwent amniocentesis at pregnancy Week 19 due to a high possibility of trisomy chromosome 6, as indicated by noninvasive prenatal testing (NIPT). However, fluorescence in situ hybridization (FISH) and whole-exome sequencing (WES) revealed no abnormalities. Subsequently, chromosomal microarray analysis (CMA) detected uniparental disomy of chromosome 6. Additionally, an ultrasound examination at 28 weeks of gestation revealed intrauterine growth restriction (IUGR). Given these findings, the parents made the decision to terminate the pregnancy. Conclusions: The combination of genetic counseling, FISH, karyotype analysis, WES, CMA, NIPT, and prenatal ultrasound can provide valuable insights for the prenatal diagnosis of UPD. These diagnostic approaches play a crucial role in identifying and managing cases of UPD, primarily when associated with intrauterine growth restrictions.
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Retardo do Crescimento Fetal , Dissomia Uniparental , Gravidez , Humanos , Feminino , Adulto , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genética , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/genética , Hibridização in Situ Fluorescente , Cromossomos Humanos Par 6 , Mosaicismo , TrissomiaRESUMO
Context: The identification of a patient's constitution in Traditional Chinese Medicine (TCM) allows physicians to understand his or her risk for different diseases, forecast the mechanism of disease development, and direct treatment strategies, such as herbs and/or acupuncture. However, very few large-scale clinical trials have occurred on the relationships of the TCM constitution to lifestyles and diseases. Objective: The study intended investigate the complex and systematic relationship between the TCM constitution and lifestyles to provide solutions for adjusting unbalanced constitutions and maintaining a balanced constitution and health state among people of various lifestyles in Jilin, China. Design: The research team conducted a randomized cross-sectional survey. Setting: The study took place in Jilin Province in China. Participants: Participants were 1755 residents of Jilin Province in China, 794 men and 961 women, between September 2006 and February 2013. Outcome Measures: The research team: (1) collected participants' data using a basic informational and lifestyle questionnaire and the Constitution in Chinese Medicine Questionnaire (CCMQ); (2) used descriptive analysis to illustrate demographic characteristics and the distribution of TCM constitutions; (3) conducted multivariate logistic regressions to explore potential factors influencing the Deficiency, Excess, Gentleness, and Special-diathesis constitutions. Results: Approximately one-half of participants in Jilin, China had an unbalanced constitution and one-third had Deficiency constitutions. Lifestyles and disease histories were significant influencing factors for the unbalanced constitutions. Of the 1755 participants, 757 had the Gentleness constitution (43.1%); the remaining participants had unbalanced constitutions, including 501 with a Deficiency constitution (28.6%), 423 with an Excess constitution (24.1%), and 74 with a Special-Diathesis constitution (4.2%). Regarding the influencing factors, the Deficiency constitutions were significantly related to lifestyle factors-especially gender, age, exercise, and diet: (21) the Qi-deficiency constitution was significantly related to excessive exercise and chronic bronchia; (2) the Yang-deficiency constitution was significantly related to female gender and prefer to hot food; and (3) the Yin-deficiency constitution was significantly related to age, from 46 to ≥66, and the barbecue diet. The Excess constitutions were related to medical histories: (1) the Phlegm-dampness and Blood-stasis constitutions were both significantly related to cardio-cerebrovascular disease and hyperlipidemia; (2) the Dampness-heat constitution was significantly related to liver disease and osteoporosis; (3) the Qi-depression constitution was significantly related to liver disease and chronic bronchia. The Gentleness constitution was significantly related to a greasy diet, and the Special-diathesis constitution was significantly related to allergies. Conclusions: The identification of TCM constitutions would be beneficial to early identification of potential risk factors and could contribute to the creation of more comprehensive guidelines for health organizations. Controlling the factors influencing the TCM constitutions and using health management plans based on the TCM constitution could help people with unbalanced constitutions to adjust their lifestyles and improve their health.
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BACKGROUND: Spontaneous preterm birth is challenging to prevent. Only few predictors of spontaneous preterm birth risk have been reported, and further studies on spontaneous preterm birth should be conducted to reduce the number of cases. PURPOSE: The aim of the present study was to explore if anti-ß2-glycoprotein I antibody can be used to predict the risk of spontaneous preterm birth, and its clinical value in assessing the risk of spontaneous preterm birth. METHODS: A total of 302 pregnant women who had delivered between January 2019 and December 2021 were enrolled into the study. The subjects were assigned to the case group (28-33+6 weeks, n = 41; 34-36+6 weeks, n = 96) and control group (37-42 weeks, n = 165) according to the gestational period. The age, body mass index, and gestational days of the two groups were recorded. Blood samples were collected and the levels of anti-ß2-glycoprotein I antibody, white blood cell, red blood cell, hemoglobin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, glucose, triglyceride, and total cholesterol were evaluated. Pregnant women diagnosed with sPTB that met the standards after evaluation by the clinician were included in the study. RESULTS: The level of anti-ß2-glycoprotein I antibody was higher in case group than in the control group [(23.93 ± 8.11)Ru/mL vs (11.50 ± 5.33)Ru/mL]. The results showed that anti-ß2-glycoprotein I antibody was an independent risk factor for spontaneous preterm birth. The area under ROC curve of anti-ß2-glycoprotein I antibody to predict spontaneous preterm birth was 0.8875 (95%CI 0.8443-0.9307). The highest predicted value of anti-ß2-glycoprotein I antibody was 16.49Ru/ml. CONCLUSION: Anti-ß2-glycoprotein I antibody has a high clinical significance and can be used by clinicians to evaluate the probability of spontaneous preterm birth.
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Nascimento Prematuro , Gravidez , Humanos , Recém-Nascido , Feminino , Nascimento Prematuro/prevenção & controle , Biomarcadores , Curva ROC , Fatores de Risco , Autoanticorpos , GlicoproteínasRESUMO
INTRODUCTION: Small cell lung cancer (SCLC) is a heterogeneous malignancy with dismal prognosis. However, few studies have conducted on the metabolic heterogeneity in SCLC. OBJECTIVE: We therefore identify SCLC classifications using untargeted metabolomics and lipidomics. We also compared their survival and the immunotherapy responses. METHODS: Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis was performed in 191 SCLC serum samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to identify metabolic pathways. The Kaplan-Meier and log-rank test were used to analyze the survival curves. The univariate and multivariate Cox proportional hazards regression models were used to evaluate prognostic factors for OS in patients with SCLC. RESULTS: Distinct subtypes of SCLC were identified by consensus clustering algorithm using partioning around medoids (pam) based on untargeted metabolomics and lipidomics. Four distinct subtypes of SCLC were identified, with distinct metabolic pathways. Subgroup 2 had the longest survival whereas Subgroup 1 had the shortest. Subtype 2 benefited most from immunotherapy in OS, as in contrast to Subtype 3 with shortest survival. CONCLUSION: Our study revealed the metabolic heterogeneity in SCLC and identified four subtypes with distinct metabolic features. It indicates promising therapeutic and prognostic value that may guide treatment for SCLC. The subtype-specific clinical trials may be designed and would be instructive for drug development.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Lipidômica , Cromatografia Líquida , Metabolômica , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to significantly improve the survival of patients with advanced lung adenocarcinoma (LUAD). However, only limited proportion of patients could benefit from ICIs. Novel biomarkers with strong predictability are needed for clinicians to maximize the efficacy of ICIs. Our study aimed to identify potential biomarkers predicting ICIs efficacy in LUAD. METHODS: The Cancer Genome Atlas (TCGA) PanCancer Atlas studies in cBioportal were used to evaluate the mutation frequency of ANK2 across multiple cancers. Clinical and mutational data for LUAD from ICIs-treated cohorts (Hellmann et al. and Rizvi et al.) were collected to explore the correlation between ANK2 mutation and clinical outcomes. In addition, the relationship between ANK2 expression and clinical outcomes was analyzed using LUAD data from TCGA and Gene Expression Omnibus. Furthermore, the impact of ANK2 mutation and expression on the tumor immune microenvironment of LUAD was analyzed using TCGA and TISIDB databases. RESULTS: Patients with ANK2 mutation benefited more from ICIs. In ICIs-treated cohort, prolonged progression-free survival (PFS) (median PFS: NR (not reached) vs. 5.42 months, HR (hazard ratio) 0.31, 95% CI 0.18-0.54; P = 0.0037), improved complete response rate (17.65% vs. 1.85%, P = 0.0402), and improved objective response rate (64.71% vs. 24.07%, P = 0.0033) were observed in LUAD patients with ANK2 mutation compared to their wild-type counterparts. Regarding ANK2 expression, it was observed that ANK2 expression was decreased in LUAD (P < 0.05) and a higher level of ANK2 expression was associated with longer overall survival (HR 0.69, 95% CI 0.52-0.92; P = 0.012) in TCGA LUAD cohort. Moreover, ANK2 mutation or higher ANK2 expression correlated with enhanced antitumor immunity and "hot" tumor microenvironment in LUAD, which could be potential mechanisms that ANK2 mutation facilitated ICIs therapy and patients with higher ANK2 expression survived longer. CONCLUSION: Our findings suggest that ANK2 mutation or increased ANK2 expression may serve as a favorable biomarker for the efficacy of ICIs in patients with LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Biomarcadores , Bases de Dados Factuais , Mutação , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Microambiente Tumoral , Anquirinas/genéticaRESUMO
Sweet sorghum is a C4 crop that can be grown for silage forage, fiber, syrup and fuel production. It is generally considered a salt-tolerant plant. However, the salt tolerance ability varies among genotypes, and the mechanism is not well known. To further uncover the salt tolerance mechanism, we performed comparative transcriptome analysis with RNA samples in two sweet sorghum genotypes showing different salt tolerance abilities (salt-tolerant line RIO and salt-sensitive line SN005) upon salt treatment. These response processes mainly focused on secondary metabolism, hormone signaling and stress response. The expression pattern cluster analysis showed that RIO-specific response genes were significantly enriched in the categories related to secondary metabolic pathways. GO enrichment analysis indicated that RIO responded earlier than SN005 in the 2 h after treatment. In addition, we identified more transcription factors (TFs) in RIO than SN005 that were specifically expressed differently in the first 2 h of salt treatment, and the pattern of TF change was obviously different. These results indicate that an early response in secondary metabolism might be essential for salt tolerance in sweet sorghum. In conclusion, we found that an early response, especially in secondary metabolism and hormone signaling, might be essential for salt tolerance in sweet sorghum.
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Tolerância ao Sal/genética , Plantas Tolerantes a Sal/genética , Sorghum/genética , Transcriptoma/genética , Grão Comestível/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Genótipo , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genéticaRESUMO
Due to climate change, drought has become a severe abiotic stress that affects the global production of all crops. Elucidation of the complex physiological mechanisms underlying drought tolerance in crops will support the cultivation of new drought-tolerant crop varieties. Here, two drought-tolerant lines, RIL70 and RIL73, and two drought-sensitive lines, RIL44 and RIL93, from recombinant inbred lines (RIL) generated from maize drought-tolerant line PH4CV and drought-sensitive line F9721, were selected for a comparative RNA-seq study. Through transcriptome analyses, we found that gene expression differences existed between drought-tolerant and -sensitive lines, but also differences between the drought-tolerant lines, RIL70 and RIL73. ZmbHLH124 in RIL73, named as ZmbHLH124T-ORG which origins from PH4CV and encodes a bHLH type transcription factor, was specifically up-regulated during drought stress. In addition, we identified a substitution in ZmbHLH124 that produced an early stop codon in sensitive lines (ZmbHLH124S-ORG ). Overexpression of ZmbHLH124T-ORG , but not ZmbHLH124S-ORG , in maize and rice enhanced plant drought tolerance and up-regulated the expression of drought-responsive genes. Moreover, we found that ZmbHLH124T-ORG could directly bind the cis-acting elements in ZmDREB2A promoter to enhance its expression. Taken together, this work identified a valuable genetic locus and provided a new strategy for breeding drought-tolerant crops.
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Secas , Zea mays , Regulação da Expressão Gênica de Plantas/genética , Melhoramento Vegetal , Estresse Fisiológico/genética , Zea mays/genéticaRESUMO
BACKGROUND: Increasing evidence has demonstrated that snoRNAs play crucial roles in tumorigenesis of various cancer types. However, researches on snoRNAs in ccRCC were very little. This study mainly aimed to validate the differential expression and the potential diagnostic value of SNORD63 and SNORD96A in ccRCC. METHODS: SnoRNAs expression was downloaded from the SNORic and TCGA database including 516 patients with ccRCC and 71 control cases. SNORD63 and SNORD96A expression were further detected in 54 tumor and adjacent FFPE ccRCC tissues, 55 plasma and 75 urinary sediment of ccRCC patients. Then, differential expression and diagnostic value of SNORD63 and SNORD96A were further calculated. RESULTS: SNORD63 and SNORD96A expression were significantly increased in ccRCC tissues compared with normal tissues from the TCGA database (both, P < 0.0001). In addition, we found that SNORD63 and SNORD96A localized in plasma and US stably after treating with RNase A. Meanwhile, SNORD63 and SNORD96A in FFPE and US were elevated in ccRCC patients (all, P < 0.0001). However, plasma SNORD63 expression had no significance while SNORD96A significantly increased in plasma of ccRCC patients. Notably, the AUC of SNORD63 in US was 0.7055, by comparison the AUC of plasma SNORD63 was only 0.5161. However, the AUC of plasma SNORD96A was up to 0.8909, by comparison the AUC of SNORD96A in US was 0.6788. Interestingly, the AUC of plasma SNORD96A in early stage ccRCC was highly up to 0.9359. CONCLUSIONS: Our findings revealed that SNORD63 in US and SNORD96A in plasma could act as the promising non-invasive diagnostic biomarkers for ccRCC patients.
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BACKGROUND: This study was aimed to investigate the application of SARS-CoV-2 IgM and IgG antibodies in diagnosis of COVID-19 infection. METHOD: This study enrolled a total of 178 patients at Huangshi Central Hospital from January to February 2020. Among them, 68 patients were SARS-CoV-2 infected, confirmed with nucleic acid test (NAT) and CT imaging. Nine patients were in the suspected group (NAT negative) with fever and other respiratory symptoms. 101 patients were in the control group with other diseases and negative to SARS-CoV-2 infection. After serum samples were collected, SARS-CoV-2 IgG and IgM antibodies were tested by chemiluminescence immunoassay (CLIA) for all patients. RESULTS: The specificity of serum IgM and IgG antibodies to SARS-CoV-2 was 99.01% (100/101) and 96.04% (97/101), respectively, and the sensitivity was 88.24% (60/68) and 97.06% (66/68), respectively. The combined detection rate of SARS-CoV-2 IgM and IgG antibodies was 98.53% (67/68). CONCLUSION: Combined detection of serum SARS-CoV-2 IgM and IgG antibodies had better sensitivity compared with single IgM or IgG antibody testing, which can be used as an important diagnostic tool for SARS-CoV-2 infection and a screening tool of potential SARS-CoV-2 carriers in clinics, hospitals, and accredited scientific laboratories.
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BACKGROUND: This study aimed to evaluate the feasibility and prognostic accuracy of incorporating the number of positive lymph nodes (PLN) into the TNM staging system for non-small cell lung cancer (NSCLC) patients. METHODS: We screened a total of 9539 patients with resected stage IA-IIIB non-small cell cancer between 2010 and 2015 from SEER database. The chi-square test was used to compare patient baseline characteristics and the X-tile model was applied to determine cut-off values for the number of PLN (nN). The X-tile model was used to screen three different cut-off values including nN = 0, nN1-3 and nN4-. Univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival (OS). Kaplan-Meier and log-rank test were used to compare survival differences. RESULTS: Based on the nN cutoffs, we conducted the univariate and multivariate Cox proportional hazards regression. The result showed that nN stage was a significant prognostic factor affecting patients' OS (all P < 0.001). We reclassified the seventh edition TNM stages of the enrolled patients with stage IA-IIIB NSCLC according to the 5-year OS rate. Hypothesized TNM substage based on the location and the number of PLN was further calculated. Then we drew survival curves for each substage, including for the current TNM stage and the hypothesized TNM stage. From the comparison of survival curves, we found that the survival curve of each substage of the hypothesized TNM classification was proportional and well distributed compared with the current TNM classification (P < 0.001). CONCLUSION: Revised TNM staging integrating locational pN stage and numerical nN stage was a more accurate prognostic determinant in patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Distribuição de Qui-Quadrado , Confiabilidade dos Dados , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Taxa de SobrevidaRESUMO
Aim: In this study, we evaluated the association between tumor location and prognosis in non-small-cell lung cancer patients. Patients & methods: The SEER database was used to screen for suitable patients using our inclusion criteria. The χ2 test was used to compare baseline patient characteristics and the Kaplan-Meier method as well as the log-rank test were used to compare survival differences. At last, univariate and multivariate Cox proportional hazards regression models were used to analyze the influence of different variables on overall survival. Results: The results found no significant difference in overall survival between patients in laterality (p = 0.071). However, patients with main bronchial tumors had worse prognosis than tumors at other locations (p < 0.001). Our results also showed that tumor location including main bronchus, upper lobe, middle lobe, lower lobe and overlapping lesion was a significant factor affecting survival (p < 0.001). Subgroup analysis revealed that regardless of histology or M stage, patients with main bronchial tumors had a worse survival compared with other tumor locations (all; p < 0.001). Interestingly, we found that patients with tumor main bronchial tumors were more likely to be squamous carcinoma and terminal Tumor, Node, Metastasis stage (all; p < 0.001). Conclusion: Non-small-cell lung cancer patients' prognosis was related to the tumor location. And patients with tumors located in main bronchus had worse outcomes than those located in other locations. Tumor primary site should be considered in treatment management and prognosis assessment.
Assuntos
Neoplasias Brônquicas/mortalidade , Neoplasias Brônquicas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Idoso , Brônquios/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Pulmão/patologia , Masculino , Estadiamento de Neoplasias/métodos , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
As a ubiquitous reaction, glucosylation controls the bioactivity of cytokinins in plant growth and development. Here we show that genetic manipulation of zeatin-O-glucosylation regulates the formation of important agronomic traits in rice by manipulating the expression of OscZOG1 gene, encoding a putative zeatin O-glucosyltransferase. We found that OscZOG1 was preferentially expressed in shoot and root meristematic tissues and nascent organs. The growth of lateral roots was stimulated in the overexpression lines, but inhibited in RNA interference lines. In shoots, knockdown of OscZOG1 expression by RNA interference significantly improved tillering, panicle branching, grain number per panicle and seed size, which are important agronomic traits for grain yield. In contrast, constitutive expression of OscZOG1 leads to negative effects on the formation of the grain-yielding traits with a marked increase in the accumulation levels of cis-zeatin O-glucoside (cZOG) in the transgenic rice plants. In this study, our findings demonstrate the feasibility of improving the critical yield-determinant agronomic traits, including tiller number, panicle branches, total grain number per panicle and grain weight by downregulating the expression level of OscZOG1. Our results suggest that modulating the levels of cytokinin glucosylation can function as a fine-tuning switch in regulating the formation of agronomic traits in rice.
Assuntos
Glucosiltransferases/metabolismo , Oryza/enzimologia , Oryza/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Característica Quantitativa Herdável , Zeatina/metabolismo , Regulação da Expressão Gênica de Plantas , Inflorescência/enzimologia , Meristema/enzimologia , Meristema/genética , Oryza/anatomia & histologia , Oryza/genética , Folhas de Planta/enzimologia , Raízes de Plantas/genética , Brotos de Planta/genética , Plantas Geneticamente Modificadas , Interferência de RNA , Plântula/genética , Plântula/crescimento & desenvolvimentoRESUMO
Objective: This study explores the inhibition of papillary thyroid carcinoma proliferation by Decorin via the EGFR/SHP2/FER pathway. Method: ology: Thirty-two pairs of papillary thyroid carcinoma tissues and adjacent normal tissues were collected for immunohistochemical analysis. Thyroid cancer cell lines with overexpressed or silenced Decorin were employed in subcutaneous tumor formation experiments in nude mice. Cell membrane proteins were extracted for Western blot and immunofluorescence analyses. Results: Reduced Decorin expression in human papillary thyroid carcinoma was associated with inhibited formation of the EGFR/SHP2/FER complex. Immunohistochemical analysis revealed lower Decorin levels in carcinoma tissues compared to adjacent normal tissues, corroborated by decreased Decorin and PTEN levels in carcinoma as shown by Western Blot. Overexpression of Decorin in mouse models diminished tumor growth, an effect reversed by Decorin silencing and mitigated by FER inhibition. Decorin modulated Rab5-GTP and Rab7-GTP levels, impacting endosome transition and subsequent signaling pathways. Conclusion: Decorin inhibits papillary thyroid carcinoma proliferation by disrupting the EGFR/SHP2/FER pathway and modulating endosomal transport.