scholarly journals Identification of prognostic-associated genes in colorectal cancer based on genome-wide expression profiles

2020 ◽  
Author(s):  
Siyu Hou ◽  
Jinfeng Zhang ◽  
Yanbo Chen ◽  
Shipeng Ning ◽  
Guozheng Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Severe Disease ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
Data Set ◽  
Go Terms

Abstract Background: Colorectal cancer (CRC), a severe disease in the world. The dysregulation of genes plays a significant role in cancer. Method: In the present study, we first identified differentially expressed genes (DEGs) of CRC in the GSE71187 data set from the Gene Expression Omnibus (GEO) database. And through GO terminology and Gene and Genome (KEGG) pathway, the up-regulated DEG and down-regulated genes were enriched. Then, we selected hub genes and studied their related prognostic value through protein-protein interaction (PPI) network and integrated bioinformatics analysis. Finally, 7 genes with prognostic value were obtained by survival analysis and multivariate Cox proportional hazards regression models, as well as verified in the Oncomine and UALCAN database.Result: A total of 3,588 DEGs were identified with 1,474 upregulated and 3,114 downregulated. Then, GO terms and Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs and down-regulated genes were mainly involved in important GO terms and KEGG pathway, for example, defense response to other organism, leukocyte differentiation and epidermis developmen. In the PP network analysis, 6 hub modules and 86 module genes were identified. In the end, 7 genes with prognostic value were obtained through survival and multi-factor analysis. They have significant differences in varying degrees at the level of DNA, mRNA and protein.Conclusion: The results of the study may provide novel insight into the genes and associated pathways involved in CRC, and aid the identifcation of novel therapeutic targets and prognostic marker of CRC.

scholarly journals Expression and Prognostic Significance of NPC1L1 in Colorectal Cancer: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Soo Min Son ◽  
Eun Ju Park ◽  
Sang Yeoup Lee ◽  
Jungin Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Chi Square ◽  
Independent Prognostic Marker ◽  
Niemann Pick

Abstract Background: Colorectal cancer (CRC) is a malignant tumor of the large intestine. Studies have shown that the development and prognosis of CRC are associated with altered lipid metabolism. Niemann-Pick C1-Like 1 (NPC1L1), the target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, the role of altered NPC1L1 expression in the development and prognosis of CRC has not yet been determined.Methods: Datasets of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) database. To compare the expression of NPC1L1 in normal and CRC tissues, datasets obtained from the GDAC platform were used. To support these results, we also analyzed other datasets from the Gene Expression Omnibus (GEO) database. Student’s t-test and chi-square test were used for the analyses. The log-rank test and multivariate Cox proportional hazards regression analysis were performed to determine whether NPC1L1 is a significant factor affecting the prognosis of CRC.Results: The mRNA expression of NPC1L1 was found to be upregulated in CRC, and was significantly associated with the N- and pathological stages, but not with the histological type, age, and sex. Moreover, an increase in NPC1L1 expression in CRC was associated with poorer survival, based on the Kaplan–Meier and multivariate regression analyses.Conclusions: High expression of NPC1L1 is associated with CRC development, pathological stage, and prognosis. The present study suggests that NPC1L1 represents a potential independent prognostic marker for CRC.

scholarly journals SELE gene as a characteristic prognostic biomarker of colorectal cancer

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110043
Author(s):  
Na Li ◽  
Honghe Xiao ◽  
Jiangli Shen ◽  
Ximin Qiao ◽  
Fenjuan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Expression Profiles ◽  
Immunohistochemical Analysis ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Cox Regression Analysis

Objective To investigate the expression and clinical value of the E-selectin gene ( SELE) in colorectal cancer (CRC). Methods Using gene expression profiles and clinicopathological data for patients with CRC from The Cancer Genome Atlas, and tumor and adjacent normal tissues from 31 patients with CRC from Xianyang Central Hospital, we studied the correlation between SELE gene expression and clinical parameters using Kaplan–Meier and Cox proportional hazards regression analyses. Results Higher expression of SELE was significantly associated with a poorer prognosis and shorter survival in patients with CRC. The median expression level of SELE was significantly higher in CRC tissues compared with healthy adjacent tissue. Cox regression analysis showed that the prognosis of CRC was significantly correlated with the expression of SELE. Immunohistochemical analysis also showed that positive expression of E-selectin increased significantly in line with increasing TNM stage. Conclusion: This study confirmed that SELE gene expression is an independent prognostic factor in patients with CRC.

Comparison of early radiological predictors of outcome in patients with colorectal cancer with unresectable hepatic metastases treated with bevacizumab

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1095-1102 ◽  
Author(s):  
Thibault Mazard ◽  
Piyaporn Boonsirikamchai ◽  
Michael J Overman ◽  
Mohamed A Asran ◽  
Haesun Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Hepatic Metastases ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Morphological Response ◽  
Colorectal Cancer Liver Metastases ◽  
Randomised Study

ObjectiveThe purpose was to validate the prognostic value of an early optimal morphological response on CT in patients treated with bevacizumab-containing chemotherapy for unresectable colorectal cancer liver metastases (CLM). It also evaluated the prognostic value of size-based criteria and the association of optimal morphological response with the receipt of bevacizumab.Design141 patients treated first using bevacizumab and 142 patients from a randomised study evaluating the addition of bevacizumab to oxaliplatin-based chemotherapy were retrospectively analysed. Radiologists evaluated pretreatment and restaging CT scans using morphological response criteria. Responses were also assessed with size-based criteria: Response Evaluation Criteria in Solid Tumors (RECIST), early tumour shrinkage (ETS) and deepness of response (DpR). The ability of each criterion to predict progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) was determined using a univariate Cox proportional hazards model.ResultsIn both populations, median PFS was significantly longer for patients achieving an optimal morphological response (10.4 vs 6.8 months, p=0.03; and 8.3 vs 4.9 months, p<00001, respectively). Neither RECIST nor ETS responses were associated with a prolonged PFS. Median OS was longer for those with an optimal morphological response but only at second restaging in the first population (n=141, 20.8 vs 12.3 months, p=0.002). DpR but not optimal morphological response was associated with PPS. In the randomised study, an optimal morphological response was 6.2 times more likely among patients receiving bevacizumab (p<0.0001).ConclusionIn patients with unresectable CLM, early morphological response may be a better predictor of PFS than size-based response. The addition of bevacizumab improves morphological response rate.

Survival stratification for colorectal cancer via multi-omics integration using an autoencoder-based model

2021 ◽  
pp. 153537022110650
Author(s):  
Hu Song ◽  
Chengwei Ruan ◽  
Yixin Xu ◽  
Teng Xu ◽  
Ruizhi Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Target Genes ◽  
Proportional Hazards ◽  
Expression Profiles ◽  
Principal Component ◽  
Good Prognosis ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Prognosis Group

Prognosis stratification in colorectal cancer helps to address cancer heterogeneity and contributes to the improvement of tailored treatments for colorectal cancer patients. In this study, an autoencoder-based model was implemented to predict the prognosis of colorectal cancer via the integration of multi-omics data. DNA methylation, RNA-seq, and miRNA-seq data from The Cancer Genome Atlas (TCGA) database were integrated as input for the autoencoder, and 175 transformed features were produced. The survival-related features were used to cluster the samples using k-means clustering. The autoencoder-based strategy was compared to the principal component analysis (PCA)-, t-distributed random neighbor embedded (t-SNE)-, non-negative matrix factorization (NMF)-, or individual Cox proportional hazards (Cox-PH)-based strategies. Using the 175 transformed features, tumor samples were clustered into two groups (G1 and G2) with significantly different survival rates. The autoencoder-based strategy performed better at identifying survival-related features than the other transformation strategies. Further, the two survival groups were robustly validated using “hold-out” validation and five validation cohorts. Gene expression profiles, miRNA profiles, DNA methylation, and signaling pathway profiles varied from the poor prognosis group (G2) to the good prognosis group (G1). miRNA–mRNA networks were constructed using six differentially expressed miRNAs (let-7c, mir-34c, mir-133b, let-7e, mir-144, and mir-106a) and 19 predicted target genes. The autoencoder-based computational framework could distinguish good prognosis samples from bad prognosis samples and facilitate a better understanding of the molecular biology of colorectal cancer.

scholarly journals Clinical Significance and Immunologic Landscape of a Five-IL(R)-Based Signature in Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Fan ◽  
Shize Pan ◽  
Shuo Yang ◽  
Bo Hao ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Immune Cell ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Interleukin Receptors ◽  
Public Datasets

Interleukins (ILs) and interleukin receptors (ILRs) play important role in the antitumor immune response. However, the expression signature and clinical characteristics of the IL(R) family in lung adenocarcinoma (LUAD) remains unclear. The main purpose of this study was to explore the expression profile of IL(R) family genes and construct an IL(R)-based prognostic signature in LUAD. Five public datasets of 1,312 patients with LUAD were enrolled in this study. Samples from The Cancer Genome Atlas (TCGA) were used as the training set, and samples from the other four cohorts extracted from Gene Expression Omnibus (GEO) database were used as the validation set. Additionally, the profile of IL(R) family signature was explored, and the association between this signature and immunotherapy response was also analyzed. Meanwhile, the prognostic value was compared between this IL(R)-based signature and different immunotherapy markers. A signature based on five identified IL(R)s (IL7R, IL5RA, IL20RB, IL11, IL22RA1) was constructed using the TCGA dataset through univariate/multivariable Cox proportional hazards regression and least absolute shrinkage and selection operator (LASSO) Cox analysis. These cases with LUAD were stratified into high- and low-risk group according to the risk score. This signature showed a strong prognostic ability, which was verified by the five independent cohorts and clinical subtypes. The IL(R)-based models presented unique characteristics in terms of immune cell infiltration and immune inflammation profile in tumor microenvironment (TME). Biological pathway analysis confirmed that high-risk patients showed significant T- and B-cell immunosuppression and rapid tumor cell proliferation. More importantly, we researched the relationship between this IL(R)-based signature and immune checkpoints, tumor mutation burden (TMB), tumor purity and ploidy, and tumor immune dysfunction and exclusion (TIDE) score, which confirmed that this signature gave the best prognostic value. We first provided a robust prognostic IL(R)-based signature, which had the potential as a predictor for immunotherapy response to realize individualized treatment of LUAD.

Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen
Keyword(s):  
Young People ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Birth Registry ◽  
Data Set ◽  
Parental Suicide ◽  
The Impact ◽  
Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

scholarly journals Prognostic value of MRI-measured tumor thickness in patients with tongue squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ki-Sun Park ◽  
Yangsean Choi ◽  
Jiwoong Kim ◽  
Kook-Jin Ahn ◽  
Bum-soo Kim ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Correlation Coefficients ◽  
Cox Proportional Hazards ◽  
Tumor Thickness ◽  
Tongue Squamous Cell Carcinoma ◽  
Depth Of Invasion

AbstractThis study aimed to assess the prognostic value of MRI-measured tumor thickness (MRI-TT) in patients with tongue squamous cell carcinoma (SCC). This single-center retrospective cohort study included 133 pathologically confirmed tongue SCC patients between January 2009 and October 2019. MRI measurements of tongue SCC were based on axial and coronal T2-weighted (T2WI) and contrast-enhanced T1-weighted (CE-T1WI) images. Two radiologists independently measured MRI-TT. Intraclass correlation coefficients (ICC) were calculated for inter-rater agreements. Spearman’s rank correlation between MRI-TT and pathologic depth of invasion (pDOI) was assessed. Cox proportional hazards analyses on recurrence-free (RFS) and overall survival (OS) were performed for MRI-TT and pDOI. Kaplan–Meier survival curves were plotted with log-rank tests. The intra- and inter-rater agreements of MRI-TT were excellent (ICC: 0.829–0.897, all P < 0.001). The correlation between MRI-TT and pDOI was good (Spearman’s correlation coefficients: 0.72–0.76, P < 0.001). MRI-TT were significantly greater than pDOI in all axial and coronal T2WI and CE-T1WI (P < 0.001). In multivariate Cox proportional hazards analysis, MRI-TT measured on axial CE-T1WI yielded a significant prognostic value for OS (hazards ratio 2.77; P = 0.034). MRI-TT demonstrated excellent intra- and inter-rater agreements as well as high correlation with pDOI. MRI-TT may serve as a prognostic predictor in patients with tongue SCC.

scholarly journals Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study

2021 ◽  
Vol 147 (5) ◽  
pp. 1407-1419
Author(s):  
Manuela Limam ◽  
Katarina Luise Matthes ◽  
Giulia Pestoni ◽  
Eleftheria Michalopoulou ◽  
Leonhard Held ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Models ◽  
Proportional Hazards ◽  
Treatment Decision ◽  
Tumor Stage ◽  
Primary Treatment ◽  
Cox Proportional Hazards ◽  
Men And Women ◽  
Logistic Regression Models ◽  
Comorbidity Index

Abstract Background Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. Methods Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. Results Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. Conclusion The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.

scholarly journals Association Between Informant-Reported Sleep Disturbance and Incident Dementia: An Analysis of the National Alzheimer’s Coordinating Center Uniform Data Set

2020 ◽  
pp. 073346482096720
Author(s):  
Woojung Lee ◽  
Shelly L. Gray ◽  
Douglas Barthold ◽  
Donovan T. Maust ◽  
Zachary A. Marcum
Keyword(s):  
Older Adults ◽  
Sleep Disturbance ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cognitive Screening ◽  
Cognitive Level ◽  
Data Set ◽  
Cox Proportional Hazards Models ◽  
Incident Dementia ◽  
Normal Cognition

Informants’ reports can be useful in screening patients for future risk of dementia. We aimed to determine whether informant-reported sleep disturbance is associated with incident dementia, whether this association varies by baseline cognitive level and whether the severity of informant-reported sleep disturbance is associated with incident dementia among those with sleep disturbance. A longitudinal retrospective cohort study was conducted using the uniform data set collected by the National Alzheimer’s Coordinating Center. Older adults without dementia at baseline living with informants were included in analysis. Cox proportional hazards models showed that participants with an informant-reported sleep disturbance were more likely to develop dementia, although this association may be specific for older adults with normal cognition. In addition, older adults with more severe sleep disturbance had a higher risk of incident dementia than those with mild sleep disturbance. Informant-reported information on sleep quality may be useful for prompting cognitive screening.

scholarly journals Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Peter W. Eide ◽  
Seyed H. Moosavi ◽  
Ina A. Eilertsen ◽  
Tuva H. Brunsell ◽  
Jonas Langerud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Principal Components ◽  
Prognostic Value ◽  
Tumor Heterogeneity ◽  
Molecular Subtypes ◽  
R Package ◽  
Data Set ◽  
Primary Tumors ◽  
External Data

AbstractGene expression-based subtypes of colorectal cancer have clinical relevance, but the representativeness of primary tumors and the consensus molecular subtypes (CMS) for metastatic cancers is not well known. We investigated the metastatic heterogeneity of CMS. The best approach to subtype translation was delineated by comparisons of transcriptomic profiles from 317 primary tumors and 295 liver metastases, including multi-metastatic samples from 45 patients and 14 primary-metastasis sets. Associations were validated in an external data set (n = 618). Projection of metastases onto principal components of primary tumors showed that metastases were depleted of CMS1-immune/CMS3-metabolic signals, enriched for CMS4-mesenchymal/stromal signals, and heavily influenced by the microenvironment. The tailored CMS classifier (available in an updated version of the R package CMScaller) therefore implemented an approach to regress out the liver tissue background. The majority of classified metastases were either CMS2 or CMS4. Nonetheless, subtype switching and inter-metastatic CMS heterogeneity were frequent and increased with sampling intensity. Poor-prognostic value of CMS1/3 metastases was consistent in the context of intra-patient tumor heterogeneity.

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