scholarly journals Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer

2011 ◽  
Vol 34 (1) ◽  
pp. 88 ◽  
Author(s):  
Dong Tang ◽  
Jun Liu ◽  
Dao-rong Wang ◽  
Hai-feng Yu ◽  
Yong-kun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Precancerous Lesions ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Related Protein ◽  
Serum Samples ◽  
Cox Regression Analysis

Purpose: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). Methods: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. Results: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. Conclusion: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.

scholarly journals Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Ran Wei ◽  
Jichuan Quan ◽  
Shuofeng Li ◽  
Zhao Lu ◽  
Xu Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cancer Stemness ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mohamed Gijon ◽  
Rachael L. Metheringham ◽  
Michael S. Toss ◽  
Samantha J. Paston ◽  
Lindy G. Durrant
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
High Expression ◽  
Related Protein ◽  
Post Translational Modification

<b><i>Introduction:</i></b> Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. <b><i>Methods:</i></b> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. <b><i>Results:</i></b> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i> = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (<i>p</i> = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (<i>p</i> = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (<i>p</i> ≤ 0.0001, <i>p</i> = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i> = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. <b><i>Conclusion:</i></b> High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Chi Square ◽  
Interacting Protein ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

scholarly journals Clinicopathological and molecular differences in colorectal cancer according to location

2019 ◽  
Vol 34 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Yu-Lun Hsu ◽  
Chun-Chi Lin ◽  
Jeng-Kai Jiang ◽  
Hung-Hsin Lin ◽  
Yuan-Tzu Lan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Rank Test ◽  
Advanced Tumor Stage ◽  
Tumor Seeding ◽  
Cox Regression Analysis ◽  
Advanced Tumor ◽  
Tumor Node Metastasis Stage

Purpose: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). Materials and methods: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. Results: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). Conclusions: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-β, PIK3CA, PTEN, AKT1, and high microsatellite instability.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

scholarly journals Deep learning for glioblastoma segmentation using preoperative magnetic resonance imaging identifies volumetric features associated with survival

2020 ◽  
Vol 162 (12) ◽  
pp. 3067-3080
Author(s):  
Yizhou Wan ◽  
Roushanak Rahmat ◽  
Stephen J. Price
Keyword(s):  
Neural Network ◽  
Overall Survival ◽  
Convolutional Neural Network ◽  
Multiple Testing ◽  
Network Performance ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Ground Truth ◽  
Cox Regression Analysis ◽  
Volumetric Features

Abstract Background Measurement of volumetric features is challenging in glioblastoma. We investigate whether volumetric features derived from preoperative MRI using a convolutional neural network–assisted segmentation is correlated with survival. Methods Preoperative MRI of 120 patients were scored using Visually Accessible Rembrandt Images (VASARI) features. We trained and tested a multilayer, multi-scale convolutional neural network on multimodal brain tumour segmentation challenge (BRATS) data, prior to testing on our dataset. The automated labels were manually edited to generate ground truth segmentations. Network performance for our data and BRATS data was compared. Multivariable Cox regression analysis corrected for multiple testing using the false discovery rate was performed to correlate clinical and imaging variables with overall survival. Results Median Dice coefficients in our sample were (1) whole tumour 0.94 (IQR, 0.82–0.98) compared to 0.91 (IQR, 0.83–0.94 p = 0.012), (2) FLAIR region 0.84 (IQR, 0.63–0.95) compared to 0.81 (IQR, 0.69–0.8 p = 0.170), (3) contrast-enhancing region 0.91 (IQR, 0.74–0.98) compared to 0.83 (IQR, 0.78–0.89 p = 0.003) and (4) necrosis region were 0.82 (IQR, 0.47–0.97) compared to 0.67 (IQR, 0.42–0.81 p = 0.005). Contrast-enhancing region/tumour core ratio (HR 4.73 [95% CI, 1.67–13.40], corrected p = 0.017) and necrotic core/tumour core ratio (HR 8.13 [95% CI, 2.06–32.12], corrected p = 0.011) were independently associated with overall survival. Conclusion Semi-automated segmentation of glioblastoma using a convolutional neural network trained on independent data is robust when applied to routine clinical data. The segmented volumes have prognostic significance.

scholarly journals Predictive value of the serum RASSF10 promoter methylation status in gastric cancer

2019 ◽  
Vol 47 (7) ◽  
pp. 2890-2900 ◽  
Author(s):  
Yilin Hu ◽  
Peng Ma ◽  
Ying Feng ◽  
Peng Li ◽  
Hua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Chronic Atrophic Gastritis ◽  
Survival Times ◽  
Cox Regression Analysis ◽  
Specific Pcr

Background This study aimed to investigate whether the detection of methylation in the promoter of the Ras association domain family 10 gene ( RASSF10) in the serum of patients with gastric cancer (GC) by methylation-specific PCR (MSP) can be used as a diagnostic and prognostic indicator of GC. Methods We used MSP to examine RASSF10 methylation levels in the serum and/or tumor samples from 100 GC patients, 50 patients with chronic atrophic gastritis (CAG), and 45 healthy controls (HC). We also analyzed clinicopathological and follow-up data. Results Our results showed that the rate of serum RASFF10 promoter methylation among patients with GC (49/100) was higher than in those with CAG (1/50) or HC (0/45). Moreover, the RASSF10 methylation status was consistent between serum and tumor tissues. GC patients with serum RASSF10 promoter methylation had significantly shorter overall survival and disease-free survival times than GC patients without serum RASSF10 promoter methylation. Multivariable Cox regression analysis showed that serum RASSF10 promoter methylation and lymph node metastasis both correlated with reduced survival in GC patients. Conclusions Detection of the serum RASSF10 methylation status by MSP is feasible as a diagnostic and prognostic indicator of GC.

scholarly journals An autophagy-related long non-coding RNA signature for patients with colorectal cancer

2021 ◽  
Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
High Risk Group ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

scholarly journals A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Jun Liu ◽  
Shanqiang Zhang ◽  
Wenjie Dai ◽  
Chongwei Xie ◽  
Ji-Cheng Li
Keyword(s):  
Overall Survival ◽  
Immune Cells ◽  
Cox Regression ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Cox Regression Analysis ◽  
Pan Cancer

SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.

scholarly journals New Circulating Circular RNAs with Diagnostic and Prognostic Potential in Advanced Colorectal Cancer

2021 ◽  
Vol 22 (24) ◽  
pp. 13283
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Oskan Tasinov ◽  
Desislava P. Ivanova ◽  
George St. Stoyanov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Clinicopathological Characteristics ◽  
Rank Test ◽  
Circular Rnas ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
The Mean ◽  
New Biomarkers

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.

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