scholarly journals Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Jing Sun ◽  
Jinfeng Liu ◽  
Dan Liu ◽  
Xiongzhi Wu
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Protein Expression ◽  
Survival Time ◽  
Signaling Pathway ◽  
Median Survival ◽  
Cox Regression ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Cox Regression Analysis

Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM’s molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively ( p < 0.001 ). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.

Prospective Series of Nine Long Noncoding RNAs Associated with Survival of Patients with Glioblastoma

2018 ◽  
Vol 79 (06) ◽  
pp. 471-478 ◽  
Author(s):  
Bingxi Lei ◽  
Lei Yu ◽  
Thapa Jung ◽  
Yuefei Deng ◽  
Wei Xiang ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Regression Analysis ◽  
Survival Time ◽  
Signaling Pathway ◽  
Cox Regression ◽  
Time Dependent ◽  
Protein Coding ◽  
Cox Regression Analysis ◽  
Protein Coding Genes ◽  
Level 3

Objective To analyze the long noncoding RNA (lncRNA) expression profile of glioblastoma multiforme (GBM) and identify prognosis-related lncRNAs, as well as their related protein-coding genes and functions. Method The lncRNA expression profiles were obtained by microarray in six samples each of GBM and normal brain tissue. The lncRNAs expressed were significantly different between the two groups and used to detect their associations with patient survival time by downloading the related data from The Cancer Genome Atlas (TCGA). The total RNA-sequencing data of 152 patients diagnosed GBM level 3 with complete clinic information was downloaded. The survival time–dependent lncRNAs were identified by multivariate Cox regression analysis. For the survival time–dependent lncRNAs, we used the Pearson correlation coefficient and z test to search their associated protein-coding genes downloaded from TCGA. Functions of these genes were annotated by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results More than 1,000 antisense lncRNAs and enhancer lncRNAs were selected for analysis in this study. Data from 152 cases with RNA-seq of GBM level 3 with complete information on GBM were downloaded from the TCGA database. Univariate Cox regression analysis revealed 19 lncRNAs with survival time dependency. These nine lncRNAs were used to construct our survival model via multivariate Cox regression analysis: TP73-AS1, AC078883.3, RP11–944L7.4, HAR1B, RP4–635E18.7, HOTAIR, SAPCD1-AS1, AC104653.1, and RP5–1172N10.2. The nine lncRNAs associated with them were inputted into the DAVID database for gene ontology and KEGG function enrichment analysis. The result showed these genes were enriched with ion binding, transport, cell-cell signaling, plasma membrane parts, and more, and they were mainly related to neuroactive ligand-receptor interaction pathway, calcium signaling pathway, and the mitogen-activated protein kinase signaling pathway. Conclusion The nine lncRNAs were a set of biomarkers for the prognosis of patients with GBM, enabling a more accurate prediction of survival and revealing more biological functions.

scholarly journals Clinical Characteristics and Prognosis of Renal Cell Carcinoma With Spinal Bone Metastases

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianpo Zhai ◽  
Ning Liu ◽  
Hai Wang ◽  
Guanglin Huang ◽  
Libo Man
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Visceral Metastasis ◽  
Cox Regression Analysis

BackgroundThe prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. In this study, we aimed to define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center.MethodsThe clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis, and the pathological type of BM were investigated. All patients were followed up regularly. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis.ResultsForty-three RCC patients with sBM were collected. sBM was found synchronously in 30 patients (70%) and metachronously in 13 patients (30%). The median survival time was 30 months in 13 patients (30%) with solitary sBM and 19 months in 30 patients (70%) with multiple sBMs (P = 0.002). Visceral metastasis occurred in 12 patients (28%) with the median survival time of 17 months, while the other 31 patients (72%) had no visceral metastasis with the median survival time of 29 months (P&lt;0.001). En-block resection was done in 10 patients with median survival time of 40.1 months. Non-en-block resection were done in 33 patients with median survival time of 19.7 months (P&lt;0.001). Multivariate COX regression analysis showed that MSKCC score, number of BM, visceral metastasis, and en-block resection are the independent prognosis factors of RCC patients with sBM.ConclusionsMSKCC risk stratification, number of sBM, visceral metastasis and en-block resection are significant prognostic factors for OS in RCC patients with spinal BM. Therefore, for selected patients who has solitary spinal BM with no visceral metastasis, en-block resection of spinal BM can potentially prolong survival and is the treatment of choice.

scholarly journals Clinical characteristics and prognosis of renal cell carcinoma with spinal bone metastases

2019 ◽  
Author(s):  
Jianpo Zhai ◽  
Ning Liu ◽  
Hai Wang ◽  
Haidong Wang ◽  
Guanglin Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Visceral Metastasis ◽  
Cox Regression Analysis

Abstract Background: The prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. To define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center. Methods: The clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis and the pathological type of BM were investigated. All patients were followed up regularly. OS was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis. Results: 22 RCC patients with sBM were collected. sBM was found synchronously in 15 patients (68.2%) and metachronously in 7 patients (31.8%) . The median survival time was 30 months in 7 patients (31.8%) with solitary sBM and 19 months in 15 patients (68.2%) with multiple sBMs. Visceral metastasis occurred in 6 patients (27.3%)with the median survival time of 17 months, while the other 16 patients (72.7%) had no visceral metastasis with the median survival time of 29 months ( P =0.006). Enblock resection was done in 7 patients with median survival time of 34 months. Non-Enblock resection were done in 15 patients with median survival time of 18 months( P =0.006). Multivariate COX regression analysis showed that visceral metastasis and Enblock resection are the independent prognostic factors of RCC with sBM. Conclusions: No visceral metastasis, En-block resection are good prognostic factors for RCC with sBM. Therefore En-block resection of sBM is recommended for RCC without visceral metastasis.

scholarly journals Alternative splicing acts as an independent prognosticator in ovarian carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yan Ouyang ◽  
Kaide Xia ◽  
Xue Yang ◽  
Shichao Zhang ◽  
Li Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Alternative Splicing ◽  
Ovarian Carcinoma ◽  
Cancer Patients ◽  
Cox Regression ◽  
Excision Repair ◽  
Splicing Factors ◽  
Prognostic Signature ◽  
Cox Regression Analysis

AbstractAlternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. There are no reliable features to predict survival outcomes for ovarian cancer patients. In this study, comprehensive profiling of AS events was conducted by integrating AS data and clinical information of ovarian serous cystadenocarcinoma (OV). Survival-related AS events were identified by Univariate Cox regression analysis. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to construct the prognostic signatures within each AS type. Furthermore, we established a splicing-related network to reveal the potential regulatory mechanisms between splicing factors and candidate AS events. A total of 730 AS events were identified as survival-associated splicing events, and the final prognostic signature based on all seven types of AS events could serve as an independent prognostic indicator and had powerful efficiency in distinguishing patient outcomes. In addition, survival-related AS events might be involved in tumor-related pathways including base excision repair and pyrimidine metabolism pathways, and some splicing factors might be correlated with prognosis-related AS events, including SPEN, SF3B5, RNPC3, LUC7L3, SRSF11 and PRPF38B. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development.

Identification and Validation of a Seven m6A-related lncRNAs Signature Predicting Prognosis of Ovarian Cancer

2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Correlation Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Group ◽  
Pearson Correlation ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Pearson Correlation Analysis

Abstract Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.

scholarly journals Identification of the Novel Methylated Genes’ Signature to Predict Prognosis in INRG High-Risk Neuroblastomas

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhichao Liu ◽  
Changchun Li
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Test Group ◽  
Functional Enrichment ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Log Rank Test

Background. Neuroblastomas are the most frequent extracranial pediatric solid tumors. The prognosis of children with high-risk neuroblastomas has remained poor in the past decade. A powerful signature is required to identify factors associated with prognosis and improved treatment selection. Here, we identified a strong methylation signature that favored the earlier diagnosis of neuroblastoma in patients. Methods. Gene methylation (GM) data of neuroblastoma patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were analyzed using a multivariate Cox regression analysis (MCRA) and univariate Cox proportional hazards regression analysis (UCPHRA). Results. The methylated genes’ signature consisting of eight genes (NBEA, DDX28, TMED8, LOC151174, EFNB2, GHRHR, MIMT1, and SLC29A3) was selected. The signature divided patients into low- and high-risk categories, with statistically significant survival rates (median survival time: 25.08 vs. >128.80 months, log-rank test, P < 0.001 ) in the training group, and the validation of the signature’s risk stratification ability was carried out in the test group (log-rank test, P < 0.01 , median survival time: 30.48 vs. >120.36 months). The methylated genes’ signature was found to be an independent predictive factor for neuroblastoma by MCRA. Functional enrichment analysis suggested that these methylated genes were related to butanoate metabolism, beta-alanine metabolism, and glutamate metabolism, all playing different significant roles in the process of energy metabolism in neuroblastomas. Conclusions. The set of eight methylated genes could be used as a new predictive and prognostic signature for patients with INRG high-risk neuroblastomas, thus assisting in treatment, drug development, and predicting survival.

Homologous recombination deficiency associated with response to poly (ADP-ribose) polymerase inhibitors in ovarian cancer patients: The first real-word data from China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17543-e17543
Author(s):  
Xiaoxiang Chen ◽  
Jing Ni ◽  
Xia Xu ◽  
Wenwen Guo ◽  
Xianzhong Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Homologous Recombination ◽  
Cancer Patients ◽  
Real World ◽  
Cox Regression ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Homologous Recombination Deficiency ◽  
Polymerase Inhibitors

e17543 Background: Homologous recombination deficiency (HRD) is the first phenotypically defined predictive biomarker for Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. However, the proportion of HRD positive in real world and the relationship of HRD status with PARPi in Chinese ovarian cancer patients remains unknown. Methods: A total of sixty-four ovarian cancer patients underwent PARPi, both Olaparib and Niraparib, were enrolled from August 2018 to January 2021 in Jiangsu Institute of Cancer Hospital. HRD score which was the sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) events were calculated using tumor DNA-based next generation sequencing (NGS) assays. HRD-positive was defined by either BRCA1/2 pathogenic or likely pathogenic mutation or HRD score ≥42. Progression-free survival (PFS) was analyzed with a log-rank test using HRD status and summarized using Kaplan-Meier methodology. Univariate and multiple cox-regression analysis were conducted to investigate all possible clinical factors. Results: 71.9% (46/64) patients were HRD positive and the rest 28.1% (18/64) were HRD negative, which was higher than the HRD positive proportion reported in Western countries. The PFS among HRD positive patients was significantly longer than those HRD negative patients (medium PFS 8.9 m vs 3.6 m, hazard ratio [HR]: 0.22, p < 0.001). Among them, 23 patients who were BRCA wild type but HRD positive had longer PFS than those with BRCA wild type and HRD negative (medium PFS 9.2 m vs 3.6 m, HR: 0.20, p < 0.001). Univariate cox-regression analysis found that HRD status, previous treatment lines, secondary cytoreductive surgery (SCS) were significantly associated with PFS after PARPi treatment. After multiple regression correction, HRD status (HR: 0.39, 95% CI: [0.20-0.76], p = 0.006), ECOG score (HR: 2.53, 95% CI: [1.24-5.17], p = 0.011) and SCS (HR: 2.21, 95% CI: [1.09-4.48], p = 0.028) were the independent factors. Subgroup analysis in ECOG = 0 subgroup (N = 36), HRD positive patients had significant longer PFS than HRD negative patients (medium PFS 10.3 m vs 5.8 m, HR: 0.14, p < 0.001). Also in the subgroup of patients without SCS, PFS in patients with HRD was longer than patients without HRD (medium PFS 10.2 m vs 5.7 m, HR: 0.29, p = 0.003). Conclusions: This is the first real-world data of HRD status in ovarian cancer patients from China and demonstrate that HRD is a valid biomarker for PARP inhibitors in Chinese ovarian cancer patients.

scholarly journals Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn’s Disease

2021 ◽  
Author(s):  
Takahiko Toyonaga ◽  
Kenza Araba ◽  
Meaghan Kennedy ◽  
Benjamin Keith ◽  
Elisabeth Wolber ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Expression ◽  
Cox Regression ◽  
Multivariate Regression Analysis ◽  
Rna Seq ◽  
Cox Regression Analysis ◽  
Molecular Stratification ◽  
The Impact

Abstract Background and Aims: The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. Methods: We examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Results: Colonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037). Conclusion: Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.

Clinical factors predictive of overall survival (OS) and the identification of prognostic groups in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy on Cancer and Leukemia and Group B trial (CALGB) 39801

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7535-7535
Author(s):  
T. E. Stinchcombe ◽  
L. Hodgson ◽  
J. E. Herndon ◽  
M. J. Kelley ◽  
M. Cicchetti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Regression Analysis ◽  
Induction Chemotherapy ◽  
Median Survival ◽  
Cox Regression ◽  
Performance Status ◽  
P Value ◽  
Cox Regression Analysis ◽  
Prognostic Groups

7535 Background: CALGB 39801 was designed to test whether treatment with induction chemotherapy and concurrent chemoradiotherapy (arm B) would improve OS in comparison to identical chemoradiotherapy alone (arm A), and demonstrated no significant benefit in OS for induction therapy. The objective of this analysis was to identify factors predictive of OS, and to use relevant factors to dichotomize pts into prognostic groups. Methods: Between July 1998 and May 2002, 331 pts were studied and included in a Cox proportional hazard regression analysis investigating previously identified prognostic factors: age (< 70 vs. ≥ 70 years), gender, race/ethnicity, hemoglobin (hgb) (< 13 vs. ≥13), performance status (PS) (0 vs.1), pretreatment weight loss (wt loss) (<5% vs. ≥ 5%), and treatment arm. Results: Cox regression analysis identified weight loss ≥ 5%, age ≥ 70, PS of 1, and hgb < 13 as predictive of worse survival (p<0.05), but not treatment arm (p=0.55). The median survival for pts with 0 (n=66), 1 (n=100), 2 (n=100), or ≥ 3 (n=65) risk factors were 24, 18, 10, and 8 months, respectively (p=0.0001). The pts were dichotomized into “poor prognosis” (PP) defined as ≥2 factors (n=165) and “good prognosis” (GP) defined as ≤ 1 factors (n=166). The hazard ratio (HR) for overall survival for the PP in comparison GP was 1.88 (95% CI, 1.49 to 2.37; p-value < 0.0001); the median survival times (MST) observed were 9 and 18 months, respectively (p<0.0001). The reasons for discontinuing treatment, and the rates of hematologic and non-hematologic adverse events were similar between the two groups. In the PP group the OS was similar between arms A (n=82) and B (n=83) (HR=0.97, 95% CI, 0.70 to 1.4; p=0.34); MST of 8.7 and 9.5 months, respectively. In the GP the OS was similar between arms A (n=79) and B (n=87) (HR=0.86, 95% CI, 0.63 to 1.1; p=0.87); MST of 19.3 and 17.6 months, respectively. Conclusions: Factors predictive of OS can be used to dichotomize pts into prognostic groups. Induction chemotherapy was not beneficial in either prognostic group. No significant financial relationships to disclose.

scholarly journals Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn’s disease

2020 ◽  
Author(s):  
Takahiko Toyonaga ◽  
Kenza C. Araba ◽  
Meaghan M. Kennedy ◽  
Benjamin P. Keith ◽  
Elisabeth A. Wolber ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Expression ◽  
Cox Regression ◽  
Multivariate Regression Analysis ◽  
Rna Seq ◽  
Cox Regression Analysis ◽  
Molecular Stratification ◽  
The Impact

AbstractBackground and AimsThe host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn’s disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course.MethodsWe examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients.ResultsColonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037).ConclusionIncreased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.

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