scholarly journals Integrative Analysis of Differently Expressed Genes Reveals a 17-Gene Prognosis Signature for Endometrial Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Anna Wang ◽  
Hongyan Guo ◽  
Zaiqiu Long

Endometrial carcinoma (EC) is the fifth widely occurring malignant neoplasm among women all over the world. However, there is still lacking efficacy indicators for EC’s prognosis. Here, we analyzed two databases including an RNA-sequencing-based TCGA dataset and a microarray-based GSE106191. After normalizing the raw data, we identified 114 common genes with upregulation and 308 common genes with downregulation in both the TCGA and GSE106191 databases. Bioinformatics analysis showed that the differently expressed genes in EC were related to the IL17 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway. Furthermore, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and generated a signature featuring 17 prognosis-related genes (MAL2, ANKRD22, METTL7B, IL32, ERFE, OAS1, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2) and found that it could predict OS in EC patients. The further analysis showed that OAS1, MAL2, ANKRD22, METTL7B, and IL32 were significantly upregulated in EC samples after comparison with normal samples. However, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2 were significantly downregulated in EC samples in comparison with normal samples. And correlation analysis showed that our results showed that the expressions of 17 prognosis-related hub genes were significantly correlated based on Pearson correlation. We here offer a newly genetic biomarker for the prediction of EC patients’ prognosis.

2021 ◽  
Author(s):  
Xiangjin Hu ◽  
Sailun Wang ◽  
Jia Guo ◽  
Fang Xiong ◽  
Jun Lv

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is the fourth leading cause of cancer-related death worldwide. Ferroptosis is a form of iron-dependent programmed cell death, and is characterized by intracellular accumulation of reactive oxygen species (ROS). Long non-coding RNAs (lncRNAs), as valuable prognostic factors for HCC patients, play a vital role in regulating ferroptosis. Methods RNA-sequencing datasets and ferroptosis-related genes were retrieved from The Cancer Genome Atlas (TCGA) database and the Molecular Signature Database. we performed Pearson correlation analysis between the lncRNAs and ferroptosis-related genes, and subsequently used regression analysis (univariate Cox analysis, multivariate Cox regression analysis, and Lasso regression analysis) to screen the ferroptosis-related lncRNAs with prognostic value in HCC, the prognostic ferroptosis-related lncRNAs signature (FRLS) was finally constructed. In addition, we reevaluated the model in terms of survival, clinical characteristics, and immune microenvironment. Results Univariate Cox regression analysis revealed 34 differently expressed ferroptosis-related lncRNAs related to the prognosis of HCC. Among them, 12 ferroptosis-related lncRNAs (LUCAT1, LINC01224, THUMPD3-AS1, AC116025.2, LINC00942, SNHG10, AC131009.1, POLH-AS1, MKLN1-AS, LINC01138, LNCSRLR, AL031985.3) were regarded as independent prognosis predictors of HCC, and were incorporated into the construction of the prognostic FRLS. Patients were divided into two groups based on the prognostic FRLS. Kaplan–Meier survival plot showed that patients in the high-risk groups exhibited shorter overall survival (OS) than those in low-risk groups (P < 0.001). Compared with clinical data, the area under curve (AUC) values of the risk factors, decision curve analysis (DCA), the AUC values of different years and multivariate Cox regression suggested that the signature had better predictive power. Gene set enrichment analysis (GSEA) revealed the potential pathways of 12 ferroptosis-related lncRNAs, including sphingolipid-metabolism, mTOR signaling pathway, notch signaling pathway, homologous recombination, endocytosis, cell cycle, etc. Immune microenvironment including tumor-infiltrating immune cells, immune-related functions, checkpoint-related genes and N6-methyladenosine (m6A)-related mRNA were also significantly different between the two risk groups. Conclusions This study constructed 12 FRLS for HCC patients to predict survival, which may provide promising targets for the therapy of HCC.


2021 ◽  
Vol 12 (1) ◽  
pp. 67-75
Author(s):  
Ying Yang ◽  
Jin Wang ◽  
Shihai Xu ◽  
Fei Shi ◽  
Aijun Shan

Abstract Background Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.


2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li

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.


Respiration ◽  
2021 ◽  
pp. 1-10
Author(s):  
Claudio Tana ◽  
Fabrizio Ricci ◽  
Maria Gabriella Coppola ◽  
Cesare Mantini ◽  
Fulvio Lauretani ◽  
...  

<b><i>Background:</i></b> Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. <b><i>Methods:</i></b> We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with &#x3e;10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0–36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). <b><i>Results:</i></b> One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation <i>r</i> = 0.754; <i>R</i><sup>2</sup> = 0.568; <i>p</i> &#x3c; 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22–43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97–19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59–34.5). <b><i>Conclusion:</i></b> LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.


1999 ◽  
Vol 17 (5) ◽  
pp. 1382-1382 ◽  
Author(s):  
Helga B. Salvesen ◽  
Ole Erik Iversen ◽  
Lars A. Akslen

PURPOSE: For endometrial carcinoma patients, there is a need for improved identification of high-risk groups that may benefit from postoperative adjuvant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial carcinoma patients in a population-based setting. PATIENTS AND METHODS: All patients diagnosed with endometrial carcinoma between 1981 and 1985 in Hordaland County, Norway, were studied. The median follow-up for the survivors was 11.5 years (range, 8 to 15 years), with no patient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunohistochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spot method for calculation of MVD, and expression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic relevance. The importance of these tumor markers was investigated in univariate survival analyses and Cox regression analysis. RESULTS: The majority of traditional clinicopathologic variables was significantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic grade, MVD, as well as Ki-67, p53, and p21 protein expression, all significantly influenced survival in univariate analyses (P ≤ .05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, and p53 expression were the only variables with independent prognostic impact (P ≤ .05), whereas histologic type, histologic grade, and p21 expression had no independent influence. A group of high-risk patients with more than one unfavorable marker was identified. CONCLUSION: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information derived from routine histologic specimens identified a subgroup of high-risk endometrial carcinoma patients in this population-based study.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 519-519 ◽  
Author(s):  
Thomas Luft ◽  
Axel Benner ◽  
Sonata Jodele ◽  
Christopher E. Dandoy ◽  
Rainer F. Storb ◽  
...  

Abstract Endothelial dysfunction has been shown to be associated with severe complications and increased NRM after alloSCT. Endothelial risk markers, such as angiopoetin-2 (ANG2) serum levels and thrombomodulin single nucleotide polymorphisms can be used for pre-transplant prediction of endothelium-related complications after alloSCT (Blood 2011;118:1685; J Clin Oncol. The aim of the present study was to develop a tool for prediction of endothelial dysfunction prior to alloSCT that can be easily used in clinical practice. For this purpose, we focused on routine parameters which are used to diagnose transplant-associated thrombotic microangiopathy (TMA), which is an endothelial complication associated with high NRM. Based on the fact that TMA is defined by high creatinine, high lactate dehydrogenase (LDH), low thrombocyte counts, schistocytes, and loss of haptoglobin, we hypothesized that the simplified formula termed 'Endothelial Activation and Stress Index (EASIX)' might be valuable for predicting TMA, NRM and overall survival (OS) after alloSCT. Design: The capacity of pre-transplant EASIX ("EASIX-pre") obtained directly prior to conditioning for alloSCT for predicting TMA was tested retrospectively in 771 consecutive adult patients undergoing alloSCT in Heidelberg between 2001 and 2013 (training cohort) using cause-specific Cox regression analysis. The correlation of EASIX-pre with pre-transplant ANG2 and suppressor of tumorigenicity-2 (ST2) serum levels was assessed by Kruskal-Wallis test / Pearson correlation. The prognostic strength of EASIX-pre for NRM, time to relapse (TTR) and OS was calculated in the training cohort and in three independent validation cohorts (Berlin adults n=386, Seattle adults n=450 and Cincinnati children n=247) by calculating the prediction error (integrated Brier score), concordance index, and calibration index. Different intensities of conditioning (MAC+RIC+non-MAC) as well as all donor types and all degrees of HLA-matching were included. Hazard ratios (HR) were estimated to illustrate the effect of a two-fold change in EASIX-pre. Results: In the training cohort, EASIX-pre was a significant risk factor for TMA in univariable (HR=1.24, p=0.03) and in multivariable models including age, disease score, ATG, donor sex, recipient sex, graft source, diagnosis and statin intake as covariates (HR 1.28, p=0.02). EASIX-pre correlated with pre-transplant serum levels of the endothelium-related markers ANG2 and ST2. Increasing EASIX-pre was significantly associated with increasing NRM (uni: HR 1.22, p<0.001, multi: HR 1.22, p=0.001) and decreasing OS (univariable: HR 1.13, p=0.002, multivariable: HR 1.11, p=0.01), but not TTR (uni: HR 1.01, p=0.77, multi: HR 1.00, p=0.95) following allo-SCT. Model validation for prediction of NRM and OS by EASIX-pre was successfully done in two independent cohorts of adult patients. In contrast, the adult model for EASIX-pre failed to predict outcome in pediatric patients, which might be explained by the different diseases and comorbidities of adults and children. In order to visualize the clinical value of assessing EASIX-pre, Figure 1 showsKaplan-Meier estimates of OS after alloSCT according to the EASIX-pre derived cutoff in Heidelberg for each cohort separately. Conclusions: The novel and easy to assess EASIX-pre score is a powerful predictor of NRM and overall mortality in adult alloSCT recipients which might be helpful for pre-transplant definition of the individual transplant risk. Disclosures Dreger: Novartis: Consultancy; Janssen: Consultancy; Roche: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Gilead: Consultancy.


2016 ◽  
Vol 26 (6) ◽  
pp. 1137-1142 ◽  
Author(s):  
Yiqing Xu ◽  
Charlotte Burmeister ◽  
Rabbie K. Hanna ◽  
Adnan Munkarah ◽  
Mohamed A. Elshaikh

ObjectiveFactors predictive of survival after recurrent early-stage endometrial carcinoma have not been thoroughly investigated. The purpose of this study was to explore factors that impact disease-specific survival (DSS) and overall survival (OS) after recurrence in women with early-stage endometrial carcinoma.Materials and MethodsAfter institutional review board approval, we identified 104 women with 2009 International Federation of Gynecology and Obstetrics stage I to II uterine endometrioid carcinoma who developed disease recurrence between January 1990 and December 2014. The Kaplan-Meier approach and Cox regression analysis were used to assess DSS and OS after recurrence and to determine factors influencing these survival end points.ResultsMedian age of the study cohort was 65 years with a median follow-up time of 42.8 months after hysterectomy. Median time to recurrence was 15.8 months. Recurrences were diagnosed in 60 patients (57.7%) who were originally managed with observation after hysterectomy and in 44 patients (42.3%) who were initially managed with adjuvant radiation treatment. Fifty-six patients (54%) had pelvic recurrence (vaginal and/or pelvic), whereas 48 (46%) had extrapelvic recurrence. Five-year DSS and OS for the entire study population was 44% and 37%, respectively. Five-year DSS and OS were longer for patients with pelvic recurrence compared with patients with extrapelvic recurrence (66% vs 18% and 55% vs 17%, P < 0.0001). Five-year DSS was also longer for radiation-naive patients than for radiation-treated patients (51% vs 34%, P = 0.023). On multivariate analysis of DSS and OS, pelvic recurrence (P < 0.001) was the only significant predictor of longer DSS and OS.ConclusionsIn women with recurrent early-stage endometrioid carcinoma, our study suggests that site of recurrence (pelvic vs extra pelvic) is the only predictor of survival. In addition, we found that radiation naivete and pelvic recurrence correlated with longer DSS and OS.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jinhui Liu ◽  
Mengting Xu ◽  
Zhipeng Wu ◽  
Yan Yang ◽  
Shuning Yuan ◽  
...  

Increasing numbers of biomarkers have been identified in various cancers. However, biomarkers associated with endometrial carcinoma (EC) remain largely to be explored. In the current research, we downloaded the RNA-seq data and corresponding clinicopathological features from the Cancer Genome Atlas (TCGA) database. We conducted an expression analysis, which resulted in RILPL2 as a novel diagnostic biomarker in EC. The dysregulation of RILPL2 in EC was also validated in multiple datasets. The correlations between clinical features and RILPL2 expression were assessed by logistic regression analysis. Then, Kaplan-Meier analysis, univariate and multivariate Cox regression analysis were performed to estimate prognostic values of RILPL2 in the TCGA cohort, which revealed that increased level of RILPL2 was remarkably associated with better prognosis and could act as an independent prognostic biomarker in patients with EC. Moreover, correlation analysis of RILPL2 and tumor-infiltrating immune cells (TIICs) indicated that RILPL2 might play a critical role in regulating immune cell infiltration in EC and is related to immune response. Besides, high methylation level was a significant cause of low RILPL2 expression in EC. Subsequently, weighted gene co-expression network analysis (WGCNA) and enrichment analysis were conducted to explore the RILPL2-involved underlying oncogenic mechanisms, and the results indicated that RILPL2 mainly regulated cell cycle. In conclusion, our findings provided evidence that downregulation of RILPL2 in EC is an indicator of adverse prognosis and RILPL2 may act as a promising target for the therapeutics of EC.


2020 ◽  
Author(s):  
Qing Zhang ◽  
Qingyu Liang ◽  
Gefei Guan ◽  
Wen Cheng ◽  
Lianhe Yang ◽  
...  

Abstract Background: Vitamins not only play a pivotal role in maintaining homeostasis of the body, but also have complex impacts on the occurrence and progression of tumors. However, the effects of vitamins on glioma and the underlying mechanism have not been fully elucidated. Methods: Vitamin -related genes were extracted from the Molecular Signature Database v7.1 (MSigDB). The overlapping overall survival (OS)-related genes in The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and GSE16011 cohorts screened out by univariate COX regression analysis were utilized to construct a risk model based on the TCGA cohort via random survival forest analysis and multivariate COX regression analysis. The powerful prognostic predictive potential of the vitamin-related risk signature was verified by Kaplan–Meier survival analysis and receiver operating characteristic (ROC) analysis in the three datasets. The ssGSEA method of the GSVA package was used for functional enrichment and immune cell component analyses. ESTIMATE score analysis was used for auxiliary analysis of glioma immune characteristics. A nomogram was constructed and assessed based on the TCGA dataset.Results: The vitamin-related six-gene (POSTN, IRX5, EEF2, RAB27A, MDM2, and ENO1) risk signature constructed based on the TCGA dataset accurately predicted the outcomes of glioma patients and credibly distinguished between different levels and molecular subtypes of glioma in the TCGA, CGGA, and GSE16011 cohorts. Gliomas with high risk scores exhibited high immune scores, low tumor purity, and immunosuppressive features. The nomogram constructed by combining the vitamin-related risk signature and clinicopathological factors precisely predicted the 1-, 3-, and 5-year OS of glioma patients.Conclusions: Our study revealed that the vitamin-related six-gene risk signature, as an independent prognostic factor, could accurately distinguish the grade, molecular subtype, and immune characteristics of glioma.


2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Bo Ma ◽  
Hui Li ◽  
Jia Qiao ◽  
Tao Meng ◽  
Riyue Yu

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is recognised as an immune active cancer, but little is known about the role of microRNAs (miRNAs) in it. In the present study, we aim to determine a prognostic and immune-related miRNAs signature (IRMS) in HNSCC. Methods: Spearman correlation analysis was used to screen out prognostic immune-related miRNAs based on single-sample gene set enrichment analysis (ssGSEA). Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to establish IRMS in HNSCC. Then, the influence of the IRMS on HNSCC was comprehensively analysed. Results: We obtained 11 prognostic immune-related miRNAs based on ssGSEA. Then an IRMS integrated with six miRNAs was established through LASSO Cox regression analysis. The stratification survival analysis indicated that IRMS was independent from other characteristics and performed favourably in the overall survival (OS) prediction. The function annotation suggested that IRMS was highly associated with the immune-related response biological processes and pathways which are so important for tumorigenesis of HNSCC. Moreover, the nomogram demonstrated that our model was identified as an independent prognostic factor. In addition, we found that IRMS was significantly correlated with the immune infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused partly by immunosuppressive microenvironment. Conclusion: We established a novel IRMS, which exhibited a potent prognostic value and could be representative of immune status in HNSCC.


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