LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia

Abstract Background Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study. Methods We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression. Results LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years). Conclusions Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.

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LINC00649 Underexpression is an Adverse Prognostic Marker in Acute Myeloid Leukemia

10.21203/rs.3.rs-39798/v1 ◽

2020 ◽

Author(s):

Chao Guo ◽

Ya-yue Gao ◽

Qian-qian Ju ◽

Chun-xia Zhang ◽

Ming Gong ◽

...

Keyword(s):

Correlation Analysis ◽

Prognostic Marker ◽

Prediction Models ◽

Cox Regression ◽

Cox Model ◽

Pearson Correlation ◽

Prognostic Significance ◽

Control Group ◽

Cpg Sites ◽

Kaplan Meier

Abstract Background long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study.Methods We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression.Results LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years).Conclusions Low expression of LINC00649 is an unfavorable prognostic marker for AML patients. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.

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Prognostic significance of lymph node dissection on stage-specific survival for patients with primary small intestine tumor treated with enterectomy: A population-based study, 2004-2015

10.21203/rs.3.rs-41043/v1 ◽

2020 ◽

Author(s):

Yifei Chen ◽

Fei He ◽

Dan Guo ◽

Yarui Li ◽

Ruhua Wang ◽

...

Keyword(s):

Small Intestine ◽

Lymph Node ◽

Lymph Nodes ◽

Cox Regression ◽

Cox Model ◽

Prognostic Significance ◽

Survival Curves ◽

Small Bowel Tumors ◽

Kaplan Meier ◽

Better Than

Abstract Background: The positive rate of lymph node detection(LND) can be used as a predictor of prognosis for patients undergoing radical resection of small bowel tumors; thorough local LND may be crucial for the accurate staging and management of the disease.The purpose of our study was to determine the effect of the LND in specific stages. Methods: This study included 5413 patients with primary small intestine tumors after enterectomy within SEER database from 2004-2015. A multivariable COX model and Kaplan-Meier plots survival curves were used to analyze survival.Results: Of the 5413 patients, 4675(86.4%) underwent lymphadenectomy, and 3896(72.0%) were moved 4 or more than 4 lymph nodes. LND was performed in 67.8%, 83.3%, 87.9%, 89.3% in pT1/2/3/4 disease. In multivariable Cox regression analyses, LND was associated with OS and CSS, and the extended LND are better than limited LND (all P<0.05 except pT2). Kaplan-Meier plots survival curves showed that LND can benefit patients.Conclusions: The removal of LND with 4 or more lymph nodes in pT1/3/4 patients has relatively obvious benefits for survival. The effect of LND with more lymph nodes is significantly better than limited LND. For pT1, pT3 and pT4, LND can be considered.

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Clinical and prognostic significance of PMN in children with glomerular C1q deposition

10.21203/rs.3.rs-23486/v1 ◽

2020 ◽

Author(s):

Ren Wang ◽

Meiqiu Wang ◽

Zhengkun Xia ◽

Chunlin Gao ◽

Zhuo Shi ◽

...

Keyword(s):

Regression Analysis ◽

Renal Dysfunction ◽

Cox Regression ◽

Age At Onset ◽

Prognostic Significance ◽

Control Group ◽

Cox Regression Analysis ◽

Pathological Characteristics ◽

Kaplan Meier ◽

Renal Prognosis

Abstract Background Currently, studies to data in MN are consistent with complement activation has an essential role in mediating renal injury, and the LP is considered to be the principal pathway in PMN. CP activation initiated by C1q which deposits are suggestive of SMN. However, C1q deposition together with IgG and C3 granular deposit is found in many cases of PMN. Currently, the clinical and prognostic significance of C1q deposition in PMN is unclear. Therefore, we conduct this single-center research to explore the clinical and prognostic significance of C1q deposition in children with PMN. Method: 73 patients with C1q deposition were enrolled in this study. According to the “Case-control matching principle”, 73 patients without C1q deposition during the same period of the renal biopsy were selected as a control group. The clinical and pathological characteristics, treatment response, and long-term renal prognosis were compared between patients with and without C1q deposition. Result A total of 146 pediatric patients with PMN included with 86 men(58.9%) and 60 women (41.1%). The median age at onset was 15.0 (14.0—16.0) years. During an average follow-up of 52.4 ± 35.6 months, 8 patients (5.5%) progressed ESKD, 12 (8.2%) patients developed ESRD or renal dysfunction. The frequency of glomerular C4 deposits in the C1q deposits group was significantly higher than no C1q deposits group (34.2% vs 5.5%, p = 0.000). There were no other distinct differences in clinical and pathological characteristics between the two groups. Glomerular IgG subclasses were available in 79 patients, there was no difference in the glomerular IgG subclass distribution between the two groups (p IgG1=0.468,p IgG2=1.000༌p IgG3=0.988༌p IgG4=0.216). The Kaplan-Meier survival analysis found that there was no difference in the renal survival of ESRD (p = 0.415) and a combined event of ESRD and/or renal dysfunction (p = 0.214) between the two groups. The logistic regression analysis (p = 0.553) and Cox regression analysis (p = 0.618) revealed that C1q deposition failed to associate with renal dysfunction. Conclusion The CP does occur in some patients of PMN. However, it may be unrelated to the progression of the disease.

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Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia

10.21203/rs.3.rs-16941/v1 ◽

2020 ◽

Author(s):

Chao Guo ◽

Qian-qian Ju ◽

Chun-xia Zhang ◽

Ming Gong ◽

Zhen-ling Li ◽

...

Keyword(s):

Cox Regression ◽

Cox Model ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

High Group ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

The Impact

Abstract Background HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. Methods We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. Results HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). Conclusions Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

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Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia

10.21203/rs.3.rs-16941/v2 ◽

2020 ◽

Author(s):

Chao Guo ◽

Qian-qian Ju ◽

Chun-xia Zhang ◽

Ming Gong ◽

Zhen-ling Li ◽

...

Keyword(s):

Cox Regression ◽

Cox Model ◽

Prognostic Significance ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

High Group ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

The Impact

Abstract Background HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. Methods We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. Results HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). Conclusions Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

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Correlation analysis of epicardial adipose tissue thickness, C-reactive protein, interleukin-6, visfatin, juxtaposed with another zinc finger protein 1, and type 2 diabetic macroangiopathy

Lipids in Health and Disease ◽

10.1186/s12944-021-01451-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yuan-Yuan Gong ◽

Hai-Ying Peng

Keyword(s):

Correlation Analysis ◽

Zinc Finger Protein ◽

Pearson Correlation ◽

Statistical Significance ◽

Healthy Control Group ◽

Control Group ◽

Diabetes Group ◽

Reactive Protein ◽

Healthy Control

Abstract Background To investigate the correlation between the thickness of epicardial adipose tissue (EAT), C-reactive protein (CRP), interleukin (IL) -6, visfatin, juxtaposed with another zinc finger protein 1 (JAZF1) and type 2 diabetic mellitus (T2DM) macroangiopathy. Methods The study enrolled 82 patients with T2DM with macroangiopathy (the Complication Group), and 85 patients with T2DM (the Diabetes Group) who were admitted to Shandong Provincial Third Hospital from February 2018 to February 2020. In addition, 90 healthy people who underwent physical examination at the same hospital during the same period were enrolled (the Healthy Control Group). Age, gender, height, weight, waist circumference (WC), hip circumference (HC), diabetic course and therapeutic drugs, waist hip ratio (WHR), and body mass index (BMI) were recorded and calculated. Results The baseline characteristics of the three groups were comparable, and the diabetic course of the Complication Group and the Diabetes Group was not significantly different (P > 0.05). The WHR of the Complication Group was higher than that of the Diabetes Group and the Healthy Control Group, with statistical significance (P < 0.05). The FPG, 2hPG, HbA1C, CRP, IL-6, Visfatin, JAZF1, HOMA-IR, EAT thickness, and baPWV of the Complication Group were all higher than those of the Diabetes Group and the Healthy Control Group (P < 0.05, respectively). The JAZF1 and FIns of the Complication Group and Diabetes Group were lower than those of the Healthy Control Group, and JAZF1 of the Complication Group was lower than the Diabetes Group with statistical significance (P<0.05, respectively). Pearson correlation analysis showed that the EAT thickness was positively correlated with CRP, IL-6, visfatin, and JAZF1 (r = 0.387, 0.451, 0.283, 0.301, respectively, all P<0.001). Pearson correlation analysis showed that baPWV was positively correlated with EAT thickness, CRP, IL-6, visfatin, and JAZF1 (r = 0.293, 0.382, 0.473, 0.286, respectively, all P < 0.001). Multivariate stepwise regression analysis showed that FPG, 2hPG, HbA1C, CRP, IL-6, visfatin, JAZF1, and EAT thickness were independent risk factors that affected T2DM macroangiopathy. Conclusions Clinical monitoring and treatment of T2DM macroangiopathy can use CRP, IL-6, Visfatin, JAZF1, and EAT thickness as new targets to delay the progression of the disease. Further research on the relationship between the above factors and the pathogenesis of T2DM macroangiopathy may be helpful provide new treatment strategies.

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

10.21203/rs.3.rs-915700/v1 ◽

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.

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Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.162 ◽

2021 ◽

Vol 7 (5) ◽

pp. 3896-3904

Author(s):

Daoting Deng ◽

Hong Zhang ◽

Junxi Liu ◽

Lina Ma ◽

Xinrui Lei ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Healthy Group ◽

Cancer Group ◽

Kaplan Meier ◽

Gastric Cancer Patients ◽

Gastric Cancer Group

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

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Down-regulation of miR-219-5p increase the risk of cancer-related mortality in patients with prostate cancer

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-139981 ◽

2021 ◽

pp. postgradmedj-2021-139981

Author(s):

Shimin Tang ◽

Hao Jiang ◽

Zhijun Cao ◽

Qiang Zhou

Keyword(s):

Prostate Cancer ◽

Prediction Model ◽

Cancer Patients ◽

Cox Regression ◽

Cox Model ◽

Risk Of Death ◽

Kaplan Meier ◽

Risk Of Progression ◽

Patient Prognosis ◽

Risk Of Cancer

IntroductionProstate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear.MethodsWe retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model’s accuracy.ResultsOf the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate’s weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death’s risk, with a corrected C-index of 0.778.ConclusionsmiR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.

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