Prognosis Of Colon Adenocarcinoma Research Articles

In silico development and clinical validation of novel 8 gene signature based on lipid metabolism related genes in colon adenocarcinoma

BackgroundChanges in lipid metabolism pathways play a major role in colon carcinogenesis and development. Hence, we conducted a systematic analysis of lipid metabolism-related genes to explore new markers that predict the prognosis of colon adenocarcinoma (COAD). MethodsThe non-negative Matrix Factorization (NMF) algorithm was applied to identify the molecular subtypes based on lipid metabolism-related genes. A weighted correlation network analysis (WCGNA) was used to identify co-expressed genes, and Lasso multivariate Cox analysis was performed to build a risk prognosis model. A timer database was used to analyze the immune infiltration of the gene signature and the GSCALite database was used for genome-wide analysis of the gene signature. ResultsTCGA-COAD samples were divided into 3 subtypes based on lipid metabolism-related genes. 2739 genes were identified by WGCNA analysis. Finally, an 8-gene signature (RTN2, FYN, HEYL, FAM69A, FBXL5, HMGN2, LGALS4, STOX1) was constructed that demonstrated good robustness in different datasets, as well as an independent risk factor for colon cancer patients’ prognosis. In addition, our model’s predictive efficacy overall was higher than that of the other published models, and the 8 genes’ expression analysis indicated that RTN2, HEYL, and STOX1 were all expressed highly significantly in COAD, while FAM69A, FBXL5, LGALS4, FYN and HMGN2 were expressed significantly poorly in cancer tissues, which was confirmed in immunohistochemistry. The 8 genes were expressed significantly differently in COAD immune subtypes and correlated with clinical variables. Genome-wide analysis revealed that the STOX1 mutation frequency was the highest, and genome methylation influenced HEYL, FAM69A, and STOX1 gene expression significantly; further, the expression of HEYL and FBXL5 was correlated positively with Copy number variation (CNV) and was regulated significantly by CNV in most cancers. FBXL5 was correlated significantly with austocystin d and bafilomycin and played an important role in anti-tumor and immunotherapy. The HEYL, FYN, FAM69A, and RTN2 genes’ expression was associated with the EMT pathway’s activation, while LGALS4 and STOX1 were associated significantly with the EMT pathway’s inhibition. ConclusionThis study constructed an 8-gene signature as a novel marker to predict colon cancer patients’ survival.

Identification of novel autophagy-related lncRNAs associated with a poor prognosis of colon adenocarcinoma through bioinformatics analysis

LncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor = − 0.15, P < 0.001; stromal score, cor = − 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.

The prognostic and predictive value of osteopontin in colon adenocarcinoma

Aim: The identification of cellular pathways in colorectal tumor biology is essential for early diagnosis, treatment, and post-treatment follow-up. Osteopontin is an extracellular matrix protein that has regulatory physiological functions and roles in apoptosis, proliferation, adhesion, invasion, and tumor metastasis. In this study, we aimed to determine the prognostic and predictive value of osteopontin in colon adenocarcinoma. Our study investigated whether osteopontin expression had any prognostic or predictive use in colon adenocarcinoma and also if there were any differences between adenocarcinoma and adenoma. Methods: Fifty of these colonic specimens were adenocarcinoma, 16 were adenomatous polyps, and 10 were nontumoral colonic tissue that served as a control group. We used a two-tiered evaluation system that examined both the staining intensity and the percentage of staining. Results: The staining scores of tumors with vascular invasion were significantly higher than those of tumors without vascular invasion (p=0.001). In addition, the tumoral tissues’ osteopontin staining scores were significantly higher than the score of polyps (p=0.001). Conclusion: If future studies support our results, we suggest that osteopontin may be an important biomarker for predicting or detecting vascular invasion in tumors and could be useful in tumor-adenomatous polyp differentiation. Therefore, osteopontin can provide helpful information in the diagnosis and prognosis of colon adenocarcinoma.

Screening of miRNAs as Prognostic Biomarkers for Colon Adenocarcinoma and Biological Function Analysis of Their Target Genes.

We constructed a prognostic risk model for colon adenocarcinoma (COAD) using microRNAs (miRNAs) as biomarkers. Clinical data of patients with COADs and miRNA-seq data were from TCGA, and the differential expression of miRNAs (carcinoma vs. para-carcinoma tissues) was assessed using R software. COAD data were randomly divided into Training and Testing Sets. A linear prognostic risk model was constructed using Cox regression analysis based on the Training Set. Patients were classified as high-risk or low-risk according to the score of the prognostic model. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate model performance. The gene targets in the prognostic model were identified and their biological functions were analyzed. Analysis of COAD and normal cell lines using qPCR was used to verify the model. There were 134 up-regulated and 140 down-regulated miRNAs. We used the Training Set to develop a prognostic model based on the expression of seven miRNAs. ROC analysis indicated this model had acceptable prediction accuracy (area under the curve=0.784). Kaplan-Meier survival analysis showed that overall survival was worse in the high-risk group. Cox regression analysis showed that the 7-miRNA Risk Score was an independent prognostic factor. The 2,863 predicted target genes were mainly enriched in the MAPK, PI3K-AKT, proteoglycans in cancer, and mTOR signaling pathways. For unknown reasons, expression of these miRNAs in cancerous and normal cells differed somewhat from model predictions. Regardless, the 7-miRNA Risk Score can be used to predict COAD prognosis and may help to guide clinical treatment.

CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer.

The chemokine ligand C-X-C motif chemokine ligand 11 (CXCL11) is involved in the progression of various cancers, but its biological roles in colorectal cancer (CRC) remain confused. Therefore, the prognostic value and underlying mechanism of CXCL11 in CRC were preliminarily evaluated. Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n = 451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, a colon adenocarcinoma (COAD) patient cohort (the Yijishan Hospital cohort, YJSHC, n = 108) was utilized for analysis of cell infiltration by immunohistochemistry. We determined the distribution of CXCL11 in tumor tissue across all TCGA cancers and found that CXCL11 expression was significantly upregulated in both COAD and rectal adenocarcinoma (READ). However, the upregulation of CXCL11 mRNA was associated with a better prognosis in COAD, but not in READ. Within the YJSHC, the patients with a high abundance of intratumoral CXCL11+ cells had prolonged survival (p = 0.001). Furthermore, we found that the high CXCL11 expression group had a higher proportion of antitumor immune cells, and a lower proportion of protumor immune cells. Additionally, we discovered the changes of gene expression and enriched immune pathway network mediated by CXCL11. Interestingly, both cytotoxic genes (IFNG, GZMA, GZMB, GZMK, GZMM, and PRF1) and immunosuppressive molecules, including PD-L1, were positively correlated with CXCL11 expression. CXCL11, which promoted antitumor immunity to benefit survival, was identified as an independent prognostic biomarker in patients with COAD.

Interfacial Curvature as a Potential Index for Prognosis of Colon Adenocarcinoma.

Tumor invasion and metastasis are complex interfacial mechanical processes between the tumor and its surrounding tissue, with the interfacial curvature of tumor playing an important role in cancer progression. In this study, the potential role of interfacial curvature in the prognosis of patients with colon adenocarcinoma is investigated. The front edge interfacial curvature of adenocarcinoma from biopsies of patients in different tumor, lymph node, and metastasis (TNM) stages are calculated and compared, and prognosis assessment is conducted using Kaplan-Meier and Cox proportional hazards regression analyses. Results reveal that patients with larger interfacial curvature of adenocarcinoma are more likely to belong to higher TNM stages. Concomitantly, in the same TNM stage, patients with increased adenocarcinoma interfacial curvature show worse prognosis with higher recurrence and lower survival rates. Besides, interfacial curvature is an independent prognostic factor for cause-specific survival and relapse-free survival among all selected patients. Mechanical models of colon adenocarcinoma invasion and metastasis are established to better understand the close association between interfacial curvature and tumor progression. The results together with hematoxylin and eosin staining indicate that metastasis in stages T3N0M0 and T3N1M0 may be linked to large interfacial curvatures. Therefore, interfacial curvature may serve as a potential index for predicting prognosis in patients with colon adenocarcinoma.

Diagnosis and prognostic value of C-X-C motif chemokine ligand 1 in colon adenocarcinoma based on The Cancer Genome Atlas and Guangxi cohort

Objective: The objective was to identify and validate C-X-C motif chemokine ligand 1(CXCL1) for diagnosis and prognosis in colon adenocarcinoma (COAD).Methods: Our current study had enrolled one The Cancer Genome Atlas (TCGA) cohort and two Guangxi cohorts to identify and verify the diagnostic and prognostic values of CXCL1 in COAD. Functional enrichment was performed by gene set enrichment analysis (GSEA).Results: In TCGA cohort, the expression of CXCL1 was significantly up-regulated in tumor tissues and decreased as the tumor stage developed. The receiver operating characteristic (ROC) curve showed that CXCL1 had a high diagnostic value for COAD. The result of Kaplan-Meier survival analysis showed that CXCL1 gene expression (P=0.045) was significantly correlated with overall survival (OS) of COAD. Results of Guangxi cohort also verified the diagnostic value of CXCL1 in COAD, and sub-group survival analyses also suggested that patients with high CXCL1 expression were related to a favorable OS (Corrected P=0.005). GSEA revealed that CXCL1 high expression phenotype was related to cytokine activity, cell apoptosis, P53 regulation pathway, and regulation of autophagy in COAD.Conclusions: In this study, we found that CXCL1 gene might be a potential diagnostic biomarker for COAD, and might serve as a prognostic biomarker for specific subgroup of COAD.

免疫相关lncRNA预测结肠腺癌预后分析

免疫相关lncRNA预测结肠腺癌预后分析

Establishment of an immune-related gene pair model to predict colon adenocarcinoma prognosis

BackgroundColon cancer is the most common type of gastrointestinal cancer and has high morbidity and mortality. Colon adenocarcinoma (COAD) is the main pathological type of colon cancer, and much evidence has supported the correlation between the prognosis of COAD and the immune system. The current study aimed to develop a robust prognostic immune-related gene pair (IRGP) model to estimate the overall survival of patients with COAD.MethodsThe gene expression profiles and clinical information of patients with colon adenocarcinoma were obtained from the TCGA and GEO databases and were divided into training and validation cohorts. Immune genes were selected that showed a significant association with prognosis.ResultsAmong 1647 immune genes, a model with 17 IRGPs was built that was significantly associated with OS in the training cohort. In the training and validation datasets, the IRGP model divided patients into the high-risk group and low-risk group, and the prognosis of the high-risk group was significantly worse (P<0.001). Univariate and multivariate Cox proportional hazard analyses confirmed the feasibility of this model. Functional analysis confirmed that multiple tumor progression and stem cell growth-related pathways were upregulated in the high-risk groups. Regulatory T cells and macrophages M0 were significantly highly expressed in the high-risk group.ConclusionWe successfully constructed an IRGP model that can predict the prognosis of COAD, providing new insights into the treatment strategy of COAD.

Alternative splicing implicated in immunity and prognosis of colon adenocarcinoma

Dysregulation of immune system is the hallmark of colon adenocarcinoma (COAD) patients. Aberrant alternative splicing (AS) is closely related to progression and immunotherapy of COAD. However, the intrinsic correlation of immune system with AS have not been elucidated. Here we identified 640 AS events related to immunescore by multi-omics data analysis. 7 key AS events were screened out and used to develop a riskscore model, the area under the ROC curve of riskscore model predicting 3-, 5-year survival probability was 0.750, 0.768. Also, the riskscore based on 7 key AS events is an independent prognostic factor. The AUC of the nomogram composed of riskscore and TMN grade reached to 0.872(3-year) and 0.841(5-year). Moreover, 11 AS events were identified to be associated with the infiltration of 8 types of immune cells. Interestingly, M1 macrophages and memory B cells had a higher infiltration in high-riskscore patients, and higher infiltration of M1 macrophages and memory B cells were significantly associated with worse prognosis. In conclusion, AS are closely related to immunescore, immunity stage and infiltrating immune cells. The riskscore is an effective diagnostic and prognostic indicator better than TMN grade, and AS events related to the immune system may be potential therapeutic targets for COAD.

IRF1-mediated immune cell infiltration is associated with metastasis in colon adenocarcinoma.

Background:Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells.Methods:We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the “Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data” algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database.Results:The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values.Conclusions:The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.

Clinical Correlation of Wnt2 and COL8A1 With Colon Adenocarcinoma Prognosis.

Wnt2 mRNA is widely expressed in various tumor tissues. Wnt2 overexpression promotes tumor growth, migration, invasion, and metastasis. However, its underlying molecular action mechanisms and clinical implications in colon adenocarcinoma (COAD) remain unclear. mRNA expression data, obtained from tissue samples, and pathophysiological data of 368 COAD patients were obtained from the Cancer Genome Atlas (TCGA) database. Further, Pearson's correlation analysis was performed to explore the correlation between the expression levels of Wnt2 and other genes in the human genome. Subsequently, a protein-protein interaction (PPI) network was constructed for hub gene identification. Overall survival and significance were determined by Kaplan-Meier analysis, and the log-rank test was used to further identify genes with prognostic significance in COAD from GEO datasets (GSE17538 and GSE39582). Subsequently, 158 tissue samples from Affiliated Hospital of Jiangnan University were used for expression verification. Gene set enrichment analysis (GSEA) was performed on high and low Wnt2 expression datasets to identify potential signaling pathways activated in COAD. In all, 10 hub genes associated with Wnt2 were screened by Pearson's correlation analysis and PPI network, with Wnt2 and COL8A1 having significantly poor prognosis by Kaplan-Meier analysis and log-rank test. Furthermore, high expressions of COL8A1 and Wnt2 were associated with poor survival both in TCGA and GEO cohorts. We further found a correlation between the expressions of Wnt2 and COL8A1 in COAD as per immunohistochemical analysis. To further elucidate the underlying molecular mechanisms of Wnt2 in COAD, we searched for pathways enriched in Wnt2 overexpressing datasets by GSEA. Our findings revealed that high Wnt2 levels were significantly associated with extracellular matrix receptor and focal adhesion pathways. Wnt2 expression correlated with COL8A1 expression in COAD; patients with high Wnt2 and COL8A1 expressions had worse survival outcomes. Pathways identified in this study prompt the molecular role of Wnt2 in COAD and provide directions to further elucidate the involved molecular mechanisms in COAD.

The Construction and Analysis of ceRNA Network and Patterns of Immune Infiltration in Colon Adenocarcinoma Metastasis.

BackgroundColon adenocarcinoma (COAD) is a malignant and lethal tumor in digestive system and distance metastasis lead to poor prognosis. The metastasis-specific ceRNAs (competitive endogenous RNAs) and tumor-infiltrating immune cells might associate with tumor prognosis and distance metastasis. Nonetheless, few studies have concentrated on ceRNAs and Immune cells in COAD.MethodsThe gene expression profile and clinical information of COAD were downloaded from TCGA and divided into two groups: primary tumors with or without distance metastasis. We applied comprehensive bioinformatics methods to analyze differential expression genes (DEGs) related to metastasis and establish the ceRNA networks. The Cox analysis and Lasso regression were utilized to screen the pivotal genes and prevent overfitting. Based on them, the prognosis prediction nomograms were established. The cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was then applied to screen significant tumor immune-infiltrating cells associated with COAD metastasis and established another prognosis prediction model. Ultimately, co-expression analysis was applied to explore the relationship between key genes in ceRNA networks and significant immune cells. Multiple databases and preliminary clinical specimen validation were used to test the expressions of key biomarkers at the cellular and tissue levels.ResultsWe explored 1 significantly differentially expressed lncRNA, 1 significantly differentially expressed miRNA, 8 survival-related immune-infiltrating cells, 5 immune cells associated with distance metastasis. Besides, 3 pairs of important biomarkers associated with COAD metastasis were also identified: T cells follicular helper and hsa-miR-125b-5p (R = −0.200, P < 0.001), Macrophages M0 and hsa-miR-125b-5p (R = 0.170, P < 0.001) and Macrophages M0 and FAS (R = −0.370, P < 0.001). Multidimensional validation and preliminary clinical specimen validation also supported the results.ConclusionIn this research, we found some significant ceRNAs (FAS and hsa-miR-125b-5p) and tumor-infiltrating immune cells (T cells follicular helper and Macrophages M0) might related to distance metastasis and prognosis of COAD. The nomograms could assist scientific and medical researchers in clinical management.

Effect of Different Expression of Immune-Related lncRNA on Colon Adenocarcinoma and Its Relation to Prognosis.

Objective To explore the expression of immune-related lncRNAs in colon adenocarcinoma and find out the effect on how these lncRNAs influence the development and prognosis of colon adenocarcinoma. Method Transcriptome data of colon adenocarcinoma from The Cancer Genome Atlas (TCGA) were downloaded, and gene sets “IMMUNE RESPONSE” and “IMMUNE SYSTEM PROCESS” were sought from the Molecular Signatures Database (MSigDB). The expression of immune-related genes was extracted that were immune-related mRNAs. Then, the immune-related lncRNAs were sought out by utilizing of the above data. Clinical traits were combined with immune-related lncRNAs, so that prognostic-related lncRNAs were identified by Cox regression. Multivariate Cox regression was built to calculate risk scores. Relationships between clinical traits and immune-related lncRNAs were also calculated. Result A total of 480 colorectal adenocarcinoma patients and 41 normal control patients' transcriptome sequencing data of tissue samples were obtained from TCGA database. 918 immune-related lncRNAs were screened. Cox regression showed that 34 immune-related lncRNAs were associated with colon adenocarcinoma prognosis. Seven lncRNAs were independent risk factors. Conclusion This study revealed that some lncRNAs can affect the development and prognosis of colon adenocarcinoma. It may provide new theory evidence of molecular mechanism for the future research and molecular targeted therapy of colon adenocarcinoma.

Data on the evaluation of FGF2 gene expression in Colorectal Cancer.

The data presented in this article is related with the research paper entitled “Evaluation of MGP gene expression in colorectal cancer”, available on Gene journal [1]. From all the transcription factors known to regulate MGP, FGF2 is the most described in colon adenocarcinoma and colon tumor cell lines, where it was shown to: i) contribute for the invasiveness potential; and ii) promote proliferation and survival of colorectal cancer cells. These in vitro studies pose the hypothesis that FGF2 associated signaling pathways could be promoting the regulation of others genes, such as MGP, that may lead to tumor progression which ultimately could result in poor prognosis in colon adenocarcinoma.

A 7-lncRNA signature associated with the prognosis of colon adenocarcinoma.

BackgroundColon adenocarcinoma (COAD) is the most common colon cancer exhibiting high mortality. Due to their association with cancer progression, long noncoding RNAs (lncRNAs) are now being used as prognostic biomarkers. In the present study, we used relevant clinical information and expression profiles of lncRNAs originating from The Cancer Genome Atlas database, aiming to construct a prognostic lncRNA signature to estimate the prognosis of patients.MethodsThe samples were randomly spilt into training and validation cohorts. In the training cohort, prognosis-related lncRNAs were selected from differentially expressed lncRNAs using the univariate Cox analysis. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were employed for identifying prognostic lncRNAs. The prognostic signature was constructed by these lncRNAs.ResultsThe prognostic model was able to calculate each COAD patient’s risk score and split the patients into groups of low and high risks. Compared to the low-risk group, the high-risk group had significant poor prognosis. Next, the prognostic signature was validated in the validation, as well as all cohorts. The receiver operating characteristic (ROC) curve and c-index were determined in all cohorts. Moreover, these prognostic lncRNA signatures were combined with clinicopathological risk factors to construct a nomogram for predicting the prognosis of COAD in the clinic. Finally, seven lncRNAs (CTC-273B12.10, AC009404.2, AC073283.7, RP11-167H9.4, AC007879.7, RP4-816N1.7, and RP11-400N13.2) were identified and validated by different cohorts. The Kyoto Encyclopedia of Genes and Genomes analysis of the mRNAs co-expressed with the seven prognostic lncRNAs suggested four significantly upregulated pathways, which were AGE-RAGE, focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways.ConclusionThus, our study verified that the seven lncRNAs mentioned can be used as biomarkers to predict the prognosis of COAD patients and design personalized treatments.

Development of a Novel Six-miRNA-Based Model to Predict Overall Survival Among Colon Adenocarcinoma Patients.

Introduction: Colon carcinoma is a common malignant tumor worldwide. Accurately predicting prognosis of colon adenocarcinoma (CA) patients may facilitate clinical individual decision-making. Many studies have reported that microRNAs (miRNAs) were associated with prognosis for patients with colon carcinoma. This study aimed to identify the prognosis-related miRNAs for predicting the overall survival (OS) of CA patients.Methods: Firstly, we analyzed the CA datasets from the Cancer Genome Atlas (TCGA), and looked for the prognosis-related miRNAs. Then, we developed a novel prediction model based on these miRNAs and the clinical characteristics. Time-dependent receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the discrimination and accuracy of the signature and model. Finally, cell function assays and bioinformatics analyses were performed to evaluate the role of these selected miRNAs in modulating biological process in CA.Results: Six prognosis-related miRNAs were included in the miRNA-based signature, and it could effectively distinguish low-risk patients and high-risk patients. Furthermore, we established a prognostic model incorporating the six-miRNA-based signature and clinical characteristics. Areas under curves (AUCs) indicated that the six-miRNA-based model has a better predictive ability than TNM stage (AUC: 0.805 vs. 0.694). The calibration plots suggested close agreement between model predictions and actual observations. GO analysis showed that the target genes of these miRNAs are mainly involved in enrichment in protein binding and regulation of transcript and cytosol. KEGG pathway enrichment analysis indicated that these genes were mainly enriched in PI3K-Akt signaling pathway. Finally, we found that the five miRNAs except miR-152 were upregulated in tumor tissues and CA cells. The functional experiments revealed that miR-1245a, miR-3682, miR-33b, and miR-5683 promoted the migratory abilities and proliferation of CA cell, whereas miR-152 showed opposite effects. However, miR-4444-2 did not influence the migratory ability and proliferation of CA cell.Conclusions: In conclusion, we developed a novel six-miRNA-based model to predict 5-year survival probabilities for CA patients. This model has the potential to facilitate individualized treatment decisions.

Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis.

Background: Peroxiredoxins (PRDXs) were reported to be associated with inflammation response in previous studies. In colon adenocarcinoma (COAD), however, their correlations and clinical significance were unclear.Methods: The RNA-seq data of 452 COAD patients with clinical information was downloaded from The Cancer Genome Atlas (TCGA) and transcripts per million (TPM) normalized. Comparisons of relative expressions of PRDXs between COAD tumor and normal controls were applied. PRDXs dy-regulations in COAD were validated via Oncomine, Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) repository. Through Tumor Immune Estimation Resource (TIMER), the immune estimation of TCGA-COAD patients was downloaded and the dy-regulated PRDXs were analyzed for their correlations with immune infiltrations in COAD. The TCGA-COAD patients were divided into younger group (age≤65 years) and older group (age>65 years) to investigate the prognostic roles of age, TNM stage, dy-regulated PRDXs and the immune infiltrations in different age groups through Kaplan-Meier survival and Cox regression analyses.Results: Three of the PRDX members showed their expressional differences both at protein and mRNA level. PRDX2 was consistently up-regulated while PRDX6 down-regulated in COAD. PRDX1 was overexpressed (mRNA) while nuclear absent (protein) in the tumor tissues. PRDX1 overexpression and PRDX6 under-expression were also shown in the stem-like colonospheres from colon cancer cells. Via TIMER, PRDX1, PRDX2, and PRDX6 were found to be negatively correlated with the immune infiltrations in COAD. Both in the younger and older patients, TNM stage had prognostic effects on their overall survival (OS) and recurrence-free survival (RFS). CD4+ T cell had independent unfavorable effects on OS of the younger patients while age had similar effects on RFS of the older ones. CD8+ T cell was independently prognostic for RFS in the two groups.Conclusions: Late diagnosis indicated poor prognosis in COAD and dy-regulated PRDXs w might be new markers for its early diagnosis. Age was prognostic and should be considered in the treatments of the older patients. Dy-regulated PRDXs were negatively correlated with immune infiltration levels. CD4+ T cell and CD8+ T cell infiltrations were prognostic in COAD and their potential as immune targets needed further investigation.

The diagnosis and prognosis values of WNT mRNA expression in colon adenocarcinoma.

WNT family genes have participated in the progression and development of many cancers, however, the association between colon adenocarcinoma (COAD) and WNTs have been rarely reported. This study investigated the significance of WNT genes expression in COAD from the standpoint of diagnosis and prognosis. The RNA-sequencing dataset of COAD was downloaded from The Cancer Genome Atlas and University of California, Santa Cruz Xena browser. The biology functions of WNT genes were investigated by biological analysis. Biological analysis of WNT family genes indicated that WNT genes were noticeably enriched in the complex process of WNT signaling pathway. The Pearson correlation analysis suggested WNT1 and WNT9B had a strong correlation. And receiver operating characteristic curves suggested that most of the genes could serve as a significant diagnostic makers in COAD (P < .05), especially WNT2 and WNT7B had high diagnostic values that the area under curve were 0.997 (95% confidence interval [0.994-1.000]) and 0.961 (95%CI [0.939-0.983]), respectively. And our multivariate survival analysis suggested the downregulated of WNT10B (P < .05) showed a favor prognosis in COAD overall survival. And the risk score model predicted that the upregulated expression of WNT10B might increase the risk of death. The very study we had conducted suggested that WNT genes had a certain connection with the diagnosis and prognosis of COAD. The messenger RNA expression of WNT2 and WNT7B might become potentially diagnostic biomarkers, and WNT10B might serve as an independent prognosis indicator for COAD.

Gene expression and methylation profiles identified CXCL3 and CXCL8 as key genes for diagnosis and prognosis of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common malignant tumors with high morbidity and mortality rates worldwide. Due to the poor clinical outcomes, it is indispensable to investigate novel biomarkers for the diagnosis and prognosis of COAD. The aim of this study is to explore key genes as potential biomarkers for the diagnosis and prognosis of COAD for clinical utility. Gene expression profiles (GSE44076 and GSE44861) and gene methylation profile (GSE29490) were analyzed to identify the aberrantly methylated-differentially expressed genes by R language and Perl software. Function enrichments were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, hub genes were identified through protein-protein interaction (PPI) network. Besides, key genes were found by the module analysis and The Cancer Genome Atlas (TCGA) survival analysis. Finally, TCGA data and quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the key genes involved in COAD. Our study found two hypomethylation-high-expression genes (CXCL3 and CXCL8) in COAD tissues compared with the adjacent normal tissues. These results were also confirmed by RT-qPCR with 25 pairs of COAD and adjacent normal tissues. Meanwhile, low expression of the two genes was associated with poor survival in patients with COAD. CXCL3 and CXCL8 may serve as key genes in the diagnosis and prognosis for COAD.