scholarly journals Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110589
Author(s):  
Zu-Xuan Chen ◽  
He-Qing Huang ◽  
Jia-Ying Wen ◽  
Li-Sha Qin ◽  
Yao-Dong Song ◽  
...  

Background Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. Methods The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. Results Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. Conclusion CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3896
Author(s):  
Karla Montalbán-Hernández ◽  
Ramón Cantero-Cid ◽  
Roberto Lozano-Rodríguez ◽  
Alejandro Pascual-Iglesias ◽  
José Avendaño-Ortiz ◽  
...  

Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.


2021 ◽  
Author(s):  
Kazuya Kusama ◽  
Rulan Bai ◽  
Yuta Matsuno ◽  
Atsushi Ideta ◽  
Toshihiro Sakurai ◽  
...  

Abstract Pregnancy loss predominantly occurs during periods between blastocyst hatching and conceptus (embryo plus extraembryonic membranes) implantation to the endometrium in cattle. Insufficient biochemical communication between conceptus and endometrium has been suspected as the primary cause for early embryonic losses. If molecules regulating this communication were identified, molecular mechanisms associated with early pregnancy success or loss could be better understood. To identify novel factors as detection markers of non-pregnant or females undergoing embryonic loss, blood sera from embryo-transferred heifers on day 7 (day 0 = day of estrus) were collected on day 17, 20, or 22, which were subjected to metabolome and global proteome iTRAQ analyses. On each sample, the metabolome analysis partly divided serum components into pregnant or not. In the iTRAQ analysis, heatmap analysis with 25 unique proteins separated into pregnant or not on day 20 or 22. Furthermore, receiver operating characteristic curve (ROC) analysis identified five candidate proteins detecting non-pregnant heifers, of which SNX5 in day 22 sera had the highest area under the curve (AUC), 0.983. We also detected SNX5 in day 22 sera from non-pregnant heifers using western blotting. These results suggest that high SNX5 in day 22 sera could predict early pregnancy loss in heifers.


2019 ◽  
Author(s):  
Gang Li ◽  
Liangtian Zhang ◽  
Nannan Han ◽  
Ke Zhang ◽  
Hengjie Li

Abstract Background: Acute lung injury (ALI) is one of the major complications of severe sepsis. This study was conducted to investigate the levels of Th22 and Th17 cells in the peripheral blood septic patients with ALI and their clinical significance. Results: A total of 479 septic patients admitted between January 2013 to January 2018 were divided into non-ALI (n = 377) and ALI groups (n = 102) based on the presence or absence of ALI. The levels of Th22 and Th17 cells, interleukin 22 (IL-22), 6 (IL-6) and 17 (IL-17) were determined. Receiver operating characteristic curve (ROC) analysis was performed to assess the early diagnostic value of Th22 and Th17 cells to predict sepsis-induced ALI. The lung injury prediction score (LIPS), IL-6, IL-17, IL-22, and levels of Th17 and Th-22 cells were 9.13, 14.02 ng/L, 13.06 ng/L, 22.90 ng/L, 8.80% and 7.40%, respectively, in the ALI patients and were significantly higher in the ALI group than in non-ALI group (P < 0.05). Pearson correlation analysis showed that LIPS, IL-17, IL-22, Th17 cells and Th22 cells were significant factors affecting sepsis-induced ALI (P < 0.05). The correlation analysis showed that the levels of Th22 cells in the peripheral blood of septic patients with ALI were positively correlated with LIPS, IL-22 and the levels of Th17 cells (P < 0.05), and the levels of Th17 cells were positively correlated with LIPS and IL-17 (P < 0.01). Multivariate logistic regression analysis showed that the LIPS (OR = 1.130), IL-17 (OR = 1.982), IL-22 (OR =2.612) and levels of Th17 (OR = 2.211) and Th22 (OR =3.230) cells were independent risk factor for ALI. The area under the curve of Th22 cells was 0.844 with a cutoff value of 6.81% to predict ALI. The sensitivity and specificity for early diagnosis of sepsis-induced ALI by Th22 cells were 78.72% and 89.13% respectively, which were better but statistically similar as compared with Th17 cells (P > 0.05). Conclusions: The levels of Th22 and Th17 cells in peripheral blood are significantly increased in septic patients with induced ALI, and may be used for early diagnose of sepsis-induced ALI.


2018 ◽  
Vol 47 (3) ◽  
pp. 925-947 ◽  
Author(s):  
Peng Lin ◽  
Dong-yue Wen ◽  
Yi-wu Dang ◽  
Yun He ◽  
Hong Yang ◽  
...  

Background/Aims: Liver cancer has the second highest cancer-related death rate globally and has relatively few targeted therapeutics. Polo-like kinase 1 (PLK1) is a fascinating trigger of the cell cycle; however, the still-rudimentary understanding of PLK1 at present is a significant barrier to its clinical applications. Here, we comprehensively clarified the clinicopathological value and potential functions of PLK1 in hepatocellular carcinoma (HCC). Methods: HCC-related microarrays, RNA-sequencing datasets and published studies were deeply mined and integrated from The Cancer Genome Atlas, Gene Expression Omnibus, ArrayExpress, Oncomine, literature databases, and immunohistochemistry experiments. Meanwhile, the associations between PLK1 expression and its clinicopathological implications and prognostic value in HCC patients were assessed. The standardized mean difference, summary receiver operating characteristic curve and the corresponding area under the curve, hazard ratios, odds ratios (ORs), and their 95% confidence intervals (CIs) were examined by STATA 12.0. Additionally, several bioinformatics methods were used to identify the potential function of PLK1 in HCC. Results: Comprehensive analyses revealed that PLK1 was significantly increased in HCC (standardized mean difference = 1.34, 95% CI: 1.03–1.65, P < 0.001). The results of diagnostic tests specified that in the summary receiver operating characteristic curve, the area under the curve was 0.88 (95% CI: 0.85–0.90). Furthermore, an elevated PLK1 level significantly predicted unfavorable overall survival (hazard ratio = 1.78, 95% CI: 1.10–2.88, P = 0.019) and was correlated with female gender (OR = 0.73, 95% CI: 0.56–0.95, P = 0.017), tumor thrombus (OR = 3.97, 95% CI: 1.46–10.78, P < 0.001), metastasis (OR = 3.46, 95% CI: 1.33–9.01, P = 0.011), pathologic stage (OR = 1.56, 95% CI: 1.17–2.07, P = 0.002), Barcelona Clinic Liver Cancer stage (OR = 5.76, 95% CI: 2.17–15.28, P < 0.001) and histologic grade (OR = 2.33, 95% CI: 1.12–487, P = 0.024). Through bioinformatics methods, we determined that enhancing the proliferative effect of PLK1 in HCC was associated with a series of hub genes and the activation of the cell cycle pathway. Conclusions: These findings substantiated that PLK1 may be an independent prognostic biomarker in HCC and may facilitate the development of targeted precision oncology.


2018 ◽  
Vol 105 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Stefano Signoroni ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Massimo Milione ◽  
Federica Perrone ◽  
...  

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.


2020 ◽  
Vol 7 ◽  
Author(s):  
Ying Luo ◽  
Ying Xue ◽  
Liyan Mao ◽  
Qun Lin ◽  
Guoxing Tang ◽  
...  

Background: Tuberculous peritonitis (TP) is a common form of abdominal tuberculosis (TB). Diagnosing TP remains challenging in clinical practice. The aim of the present meta-analysis was to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and peritoneal fluid (PF) T-SPOT for diagnosing TP.Methods: PubMed, EmBase, Cochrane, Scopus, Google scholar, China national knowledge internet, and Wan-Fang databases were searched for relevant articles from August 1, 2005 to July 5, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. Diagnostic parameters including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic curve was used to determine the area under the curve (AUC).Results: Twelve studies were eligible and included in the meta-analysis. The analysis showed that the pooled sensitivity and specificity of PB T-SPOT in diagnosing TP were 0.91 (95% CI, 0.88–0.94) and 0.78 (95% CI, 0.73–0.81), respectively, while the pooled PLR, NLR, and DOR were 4.05 (95% CI, 2.73–6.01), 0.13 (95% CI, 0.07–0.23), and 37.8 (95% CI, 15.04–94.98), respectively. On the other hand, the summary estimates of sensitivity, specificity, PLR, NLR, and DOR of PF T-SPOT for TP diagnosis were 0.90 (95% CI, 0.85–0.94), 0.78 (95% CI, 0.72–0.83), 6.35 (95% CI, 2.67–15.07), 0.14 (95% CI, 0.09–0.21), and 58.22 (95% CI, 28.76–117.83), respectively. Furthermore, the AUC of PB T-SPOT and PF T-SPOT for TP diagnosis were 0.91 and 0.94, respectively.Conclusions: Our results indicate that both PB T-SPOT and PF T-SPOT can be served as sensitive approaches for the diagnosis of TP. However, the unsatisfactory specificities of these two methods limit their application as rule-in tests for TP diagnosis. Furthermore, the standardization of the operating procedure of PF T-SPOT is further needed.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 409-409
Author(s):  
Jai Narendra Patel ◽  
Allison Mary Deal ◽  
Howard L. McLeod ◽  
Bert H. O'Neil ◽  
Christine Marie Walko

409 Background: Approximately 30% of cancer patients are obese. Controversy exists on how to best use body weight to safely and effectively dose chemotherapy. Additionally, body surface area (BSA)-based dosing is associated with high pharmacokinetic (PK) variability and is a poor indicator of optimal drug exposure. Methods: We estimated FU exposure post cycle 1, as indicated by area under the curve (AUC), in 58 colorectal cancer patients receiving mFOLFOX6 (FU 2400 mg/m2 [BSA calculated using actual body weight (ABW)] over 46 hours) +/- bevacizumab. AUCs were determined using an immunoassay at Myriad Laboratories. The primary objective was to identify variability in FU exposure in obese and non-obese patients using body mass index (BMI), BSA, and ABW. Groups were compared using two group t-tests. Results: No significant difference in AUC was observed between obese (BMI ≥ 30 kg/m2) and non-obese (< 30 kg/m2) patients. A significantly lower AUC was observed in patients with a BSA ≥ 2.0 m2 compared to those < 2.0 m2 (p=0.02). The AUC for obese and non-obese patients ranged from 7-34 and 12-38 mg*hr/L, respectively. Only 32% and 28% of obese and non-obese patients, respectively, were within the previously reported therapeutic target AUC 20-25 mg*hr/L. Males had significantly lower AUCs compared to females (mean 18.7 v 22.4, p=0.03). FU AUC was not strongly correlated with BMI, BSA, or ABW (Pearson correlation of -0.03, -0.26, and -0.15, respectively). Conclusions: BSA-based dosing is associated with variable FU exposure. Lower AUCs in patients with a BSA ≥ 2.0 m2 supports both ASCO recommendations for full-weight-based dosing in obese patients and the value of dosing assessment across patient populations. Further study of AUC-based dosing is warranted as our data do not support a reduction in variable exposure based on BMI, BSA, or ABW dosing. [Table: see text]


Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 598
Author(s):  
Norhan A. Sabbah ◽  
Wael M. Abdalla ◽  
Walid A. Mawla ◽  
Nagla AbdAlMonem ◽  
Amal F. Gharib ◽  
...  

Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients’ serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.


Author(s):  
Mahsa Roozrokh Arshadi Montazer ◽  

Background: Mild Cognitive impairment (MCI) is a primary disorder intensifies by aging. Rapid diagnosis of MCI can prevent its progression towards the development of dementia. Thus, the present study was conducted to evaluate the psychometric features of the self-assessment Persian version of Alzheimer's questionnaire (AQ) in the elderly to detect MCI. Methods: First, the Alzheimer's questionnaire was translated into the Persian language; then, content validity was evaluated by CVI and CVR method, face validity was determined by two checklists for expert panel and the elderly. Convergent validity of the MCI test with MoCA was assessed using Pearson correlation. Test-retest and internal consistency reliability using Intra-Class Correlation (ICC) and Kuder-Richardson coefficients, respectively, were evaluated; moreover, the receiver operating characteristic curve was used to determine the optimal cut-off point of self-assessment MCI test. Among 148 older people took part, 93 of them meet our inclusion criteria (aged 60 years old or older, had reading and writing skills and able to speak and communicate). Result: A translated version of the questionnaire was named “M-check”. The developed test showed good content and face validity. Statistically significant correlations were found between M-check and MoCA (r= -0.83, p < 0.05). Kuder–Richardson and ICC coefficient were obtained as 0.84 and 0.92, respectively. Area under the curve presented satisfactory values (AUC =0.852, sensitivity =0.62, specificity =0.94). Conclusion: M-check is a reliable tool that can be used as a valid and reliable instrument for assessing cognitive state and screening dementia in the elderly.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9943 ◽  
Author(s):  
Baowei Ji ◽  
Lihua Chen ◽  
Qiang Cai ◽  
Qiao Guo ◽  
Zhibiao Chen ◽  
...  

Background Glioma is the most common form of primary malignant intracranial tumor. Methods In the current study, miRNA matrix were obtained from the Chinese Glioma Genome Atlas (CGGA), and then univariate Cox regression analysis and Lasso regression analysis were utilized to select candidate miRNAs and multivariate Cox regression analysis was applied to establish a miRNA signature for predicting overall survival (OS) of glioma. The signature was assessed with the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and validated by data from Gene Expression Omnibus (GEO). Results Eight miRNAs (miR-1246, miR-148a, miR-150, miR-196a, miR-338-3p, miR-342-5p, miR-548h and miR-645) were included in the miRNA signature. The AUC of ROC analysis for 1- and 3-year OS in the CGGA dataset was 0.747 and 0.905, respectively. In the GEO dataset, The AUC for 1- and 3-year was 0.736 and 0.809, respectively. The AUC in both the CGGA and GEO datasets was similar to that based on WHO 2007 classification (0.736 and 0.799) and WHO 2016 classification (0.663 and 0.807). Additionally, Kaplan–Meier plot revealed that high-risk score patients had a poorer clinical outcome. Multivariate Cox regression analysis suggested that the miRNA signature was an independent prognosis-related factor [HR: 6.579, 95% CI [1.227−35.268], p = 0.028]. Conclusion On the whole, in the present study, based on eight miRNAs, a novel prognostic signature was developed for predicting the 1- and 3- year survival rate in glioma. The results may be conducive to predict the precise prognosis of glioma and to elucidate the underlying molecular mechanisms. However, further experimental researches of miRNAs are needed to validate the findings of this study.


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