scholarly journals MO245OUTCOME OF DIFFERENT INDUCTION REGIMENS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS ACCORDING TO THE HISTOPATHOLOGICAL CHARACTERISTICS: THE REASSESS STUDY*

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Martina Uzzo ◽  
Jennifer Scott ◽  
Alice Guerini ◽  
Jennifer O'brien ◽  
Anna Ricchiuto ◽  
...  
Keyword(s):  
High Risk ◽  
Regression Model ◽  
Cox Regression ◽  
Renal Involvement ◽  
Free Survival ◽  
Risk Class ◽  
Cox Regression Analysis ◽  
Multicenter Survey ◽  
Induction Regimen ◽  
Renal Relapse

Abstract Background and Aims Renal involvement in ANCA-associated vasculitis (AAV) impacts significantly on patients’ prognosis. The role of different induction regimens on remission rates and long-term renal outcomes according to renal histological characteristics has not been explored yet. Method AAV patients with biopsy-proven renal involvement were collected retrospectively from eleven centers and stratified according to the induction regimen employed: Rituximab (RTX), Cyclophosphamide (CYC) or both (RTX-CYC). Kidney biopsies were classified according to the Berden and Brix classifications. Renal remission rate was assessed 6 months after the induction regimen and defined as a renal Birmingham Vasculitis Activity Score (BVAS) of 0. Among patients who achieved remission at 6 months, renal relapse was defined as a renal-BVAS>0 associated with an increase in immunosuppressive treatment. ESRD was defined as an eGFR<15 ml/min/1,73m2, need for dialysis or renal transplant. Results 323 patients were identified and followed-up for a median time of 36 months (IQR 18-72). The cohort included 38% patients with GPA and 62% with MPA, 53% patients were MPO-ANCA and 41% PR3-ANCA positive. The median baseline eGFR in the overall cohort was 19 ml/min/1,73m2 (IQR 12- 34). 58% of patients were treated with CYC, 24% with RTX-CYC and 18% with RTX. According to the Berden classification, 24% biopsies were classified as Focal, 31% as Crescentic, 33% as Mixed and 12% as Sclerotic. The Brix score was assessable in 270/323 (84%) patients: 17%, 52% and 31% were respectively in the Low, Medium and High-risk class. The overall renal remission at 6 months was 90%; according to the Berden classification, 94% patients achieved remission in the Focal, 88% in the Crescentic, 91% in the Mixed and 86% in the Sclerotic class. According to the Brix risk score, 88% patients achieved remission in the High risk, 91% in the Medium and 96% in the Low-risk class. According to induction regimen employed, 91%, 90% and 90% patients achieved remission in the RTX, CYC and RTX plus CYC group respectively. In a logistic regression model adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria at onset, the induction regimen employed was not predictive of renal remission at 6 months, neither in Berden Focal plus Crescentic and Mixed plus Sclerotic classes, nor in Brix High and Low plus Medium risk classes. Of the 185 patients with at least 6 months of follow-up available after remission, 25% experienced a renal relapse. In a Cox regression model adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria at onset, the induction regimen or histological score were not predictive of renal relapse. In the unadjusted survival analysis with the Kaplan-Maier curve, patients in the Crescentic group treated with RTX had a shorter ESRD-free survival compared to the CYC group (p=0.033) and the RTX-CYC group (p=0.044); figure 1: This was confirmed also with a Cox regression analysis adjusted for sex, age, ANCA type, AAV diagnosis, creatinine and proteinuria when comparing the RTX group with the CYC one (HR 8.30 [95% CI 1.64 to 42.01], p=0.011); figure 2: While the eGFR changes over time in the Focal plus Crescentic and Mixed plus Sclerotic classes showed a similar trend between treatment groups, in the Crescentic class the median eGFR values in the RTX group tended to be lower compared to the CYC and the RTX-CYC ones; figure 3: The rate of severe infections in the RTX, CYC and RTX-CYC group was respectively 6.3, 8.5 and 8.8 per 100 patient-years during the first 12 months. Conclusion in a retrospective multicenter survey, response rates and relapse risk after different induction regimens in AAV patients with renal involvement were comparable in the overall cohort and in the different histopathological subgroups. Although in a small subset of patients, the ESRD-free survival in the Crescentic class was shorter in the RTX group compared to the CYC one.

scholarly journals Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001591
Author(s):  
Laurette van Boheemen ◽  
Samina Turk ◽  
Marian van Beers-Tas ◽  
Wouter Bos ◽  
Diane Marsman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Cox Regression ◽  
Controlled Trial ◽  
Pharmacological Intervention ◽  
Trial Participation ◽  
Double Blind ◽  
Cox Regression Analysis ◽  
Atorvastatin Group ◽  
Clinical Arthritis

ObjectivesPersons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.MethodsArthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.ResultsDue to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.ConclusionsIn this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.

scholarly journals FRI0181 ORGAN DAMAGE FREE SURVIVAL IN SOUTHERN CHINESE PATIENTS WITH ACTIVE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 674.1-674
Author(s):  
C. C. Mok ◽  
C. S. Sin ◽  
K. C. Hau ◽  
T. H. Kwan
Keyword(s):  
Lupus Nephritis ◽  
Regression Model ◽  
Cox Regression ◽  
Organ Damage ◽  
Renal Survival ◽  
Cox Regression Model ◽  
Free Survival ◽  
Renal Response

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

2017 ◽  
Vol 27 (7) ◽  
pp. 1379-1386 ◽  
Author(s):  
Rhonda Farrell ◽  
Suzanne C. Dixon ◽  
Jonathan Carter ◽  
Penny M. Webb
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Adjuvant Treatment ◽  
Cox Regression ◽  
Early Stage ◽  
Cox Regression Analysis ◽  
Cancer Study ◽  
Stage Ib ◽  
Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Regression Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
High Status ◽  
Free Survival ◽  
Pdac Tissue ◽  
Treatment Naïve

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 444-444
Author(s):  
Dimitrios Makrakis ◽  
Daniel Castellano ◽  
Ivan de Kouchkovsky ◽  
Joseph J. Park ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Overall Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Similar Proportion ◽  
Multivariable Model ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Response Table ◽  
Advanced Urothelial Carcinoma

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]

scholarly journals The impact of method of distal ureter management during radical nephroureterectomy on tumour recurrence

2014 ◽  
Vol 8 (11-12) ◽  
pp. 845 ◽  
Author(s):  
Anil Kapoor ◽  
Shawn Dason ◽  
Christopher B. Allard ◽  
Bobby Shayegan ◽  
Louis Lacombe ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumour Recurrence ◽  
Management Approach ◽  
Management Technique ◽  
Recurrence Free Survival ◽  
Radical Nephroureterectomy ◽  
Distal Ureter ◽  
Free Survival ◽  
Cox Regression Analysis

Introduction: Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multiinstitutional Canadian radical nephroureterectomy database.Methods: We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed.Results: A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease.Conclusion: Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.

scholarly journals Development of prognosis model for colon cancer based on autophagy-related genes

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang
Keyword(s):  
Colon Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Score ◽  
Cox Regression ◽  
Patient Survival ◽  
Expression Profiles ◽  
Cox Regression Analysis ◽  
Risk Patients

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.

scholarly journals Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Regression Model ◽  
Target Genes ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

scholarly journals Triglyceride glucose-body mass index in identifying high-risk groups of pre-diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chunyuan Jiang ◽  
Ruijuan Yang ◽  
Maobin Kuang ◽  
Meng Yu ◽  
Mingchun Zhong ◽  
...  
Keyword(s):  
Body Mass Index ◽  
High Risk ◽  
Diagnostic Criteria ◽  
Body Mass ◽  
Cox Regression ◽  
Risk Groups ◽  
World Health ◽  
Obese People ◽  
Cox Regression Analysis ◽  
Health Organization

Abstract Background Triglyceride glucose-body mass index (TyG-BMI) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG-BMI and pre-diabetes remains to be elucidated. Methods More than 100,000 subjects with normal glucose at baseline received follow-up. The main outcome event of concern was pre-diabetes defined according to the diagnostic criteria recommended by the American Diabetes Association (ADA) in 2018 and the World Health Organization (WHO) in 1999. A Cox proportional hazard regression model was used to evaluate the role of TyG-BMI in identifying people at high risk of pre-diabetes. Results At a mean observation period of 3.1 years, the incidence of pre-diabetes in the cohort was 3.70 and 12.31% according to the WHO and ADA diagnostic criteria for pre-diabetes, respectively. The multivariate Cox regression analysis demonstrated that TyG-BMI was independently positively correlated with pre-diabetes, and there was a special population dependence phenomenon. Among them, non-obese people, women and people under 50 years old had a significantly higher risk of TyG-BMI-related pre-diabetes (P-interaction< 0.05). Conclusions These findings suggest that a higher TyG-BMI significantly increases an individual’s risk of pre-diabetes, and this risk is significantly higher in women, non-obese individuals, and individuals younger than 50 years of age.

scholarly journals A Risk Signature of Nine Autophagy-Related Genes Associated With Immune Microenvironment and Clinical Prognosis in Wilms Tumor

2021 ◽  
Author(s):  
Shaopei Ye ◽  
Wenbin Tang ◽  
Ke Huang
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Risk Score ◽  
Cox Regression ◽  
Wilms Tumor ◽  
Risk Group ◽  
High Risk Group ◽  
Differentially Expressed ◽  
Clinical Prognosis ◽  
Cox Regression Analysis

Abstract Background: Autophagy is a biological process to eliminate dysfunctional organelles, aggregates or even long-lived proteins. . Nevertheless, the potential function and prognostic values of autophagy in Wilms Tumor (WT) are complex and remain to be clarifed. Therefore, we proposed to systematically examine the roles of autophagy-associated genes (ARGs) in WT.Methods: Here, we obtained differentially expressed autophagy-related genes (ARGs) between healthy and Wilms tumor from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology. Then univariate COX regression analysis and multivariate COX regression analysis were performed to acquire nine autophagy genes related to WT patients’ survival. According to the risk score, the patients were divided into high-risk and low-risk groups. The Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis.Results: Eighteen DEARGs were identifed, and nine ARGs were fnally utilized to establish the FAGs based signature in the TCGA cohort. we found that patients in the high-risk group were associated with mutations in TP53. We further conducted CIBERSORT analysis, and found that the infiltration of Macrophage M1 was increased in the high-risk group. Finally, the expression levels of crucial ARGs were verifed by the experiment, which were consistent with our bioinformatics analysis.Conclusions: we emphasized the clinical significance of autophagy in WT, established a prediction system based on autophagy, and identified a promising therapeutic target of autophagy for WT.

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