scholarly journals High serum Hsp70 level predicts poor survival in colorectal cancer: Results obtained in an independent validation cohort

2018 ◽  
Vol 23 (4) ◽  
pp. 539-547 ◽  
Author(s):  
László Gráf ◽  
Lóránd Barabás ◽  
Balázs Madaras ◽  
Nóra Garam ◽  
Éva Maláti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Validation Cohort ◽  
High Serum ◽  
Poor Survival ◽  
Hsp70 Level ◽  
Independent Validation

Preoperative serum microRNA-203 as a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 564-564
Author(s):  
Yuji Toiyama ◽  
Keun Hur ◽  
Yoshinaga Okugawa ◽  
C. Richard Boland ◽  
Ajay Goel
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Metastasis ◽  
Culture Media ◽  
Predictive Biomarker ◽  
High Serum ◽  
Dependent Manner ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Clinicopathological Findings

564 Background: Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. Epithelial-mesenchymal transition (EMT) is a key process that converts polarized immotile epithelial cells into motile, invasive mesenchymal cells, enabling cancer cells to gain stem cell characteristics and an aggressive malignant phenotype such as metastasis. Mir-203 has been shown to directly suppress EMT activators such as ZEB2 and SNAI1/2. However, in spite of the key functional role of miR-203 in cancer metastasis, no previous studies have investigated the clinical significance of miR-203 in patients with CRC. Methods: To examine whether CRCs secret miR-203 in vitro and vivo,we first determined extracellular miR-203 levels in CRC cell culture media. Then, we quantified miR-203 levels in serum from mice with or without metastasis. Next, we investigated miR-203 expression in 58 pairs of primary CRC (pCRC) and corresponding matching liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from CRC patients. Results: HT-29 cells released miR-203 into culture media, which was dependent on cell number and duration of culture. In addition, high serum miR-203 levels were observed in mice with liver metastasis compared to control animals (p=0.0181). Mir-203 expression was significantly upregulated in LM compared to matching pCRC tissues (p=0.0002). Serum miR-203 was significantly upregulated in a tumor stage-dependent manner (p=0.0070), and high miR-203 expression was associated with poor survival in CRC patients (p<0.0001). In contrast to serum, no significant association between miR-203 expression in CRC tissues and clinicopathological findings was recognized. High serum miR-203 expression was an independent risk factor for poor prognosis (HR=2.1) as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2), and distant organs (OR=4.4), respectively. Conclusions: High levels of serum miR-203, which may be derived from several metastatic sites, are associated with poor survival and metastasis, suggesting it is a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC.

scholarly journals Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Xu ◽  
Qing Zheng
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Validation Cohort ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Immune Checkpoints ◽  
Positive Correlation ◽  
Expression Signature ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.

scholarly journals Radiomic nomogram based on MRI to predict grade of branching type intraductal papillary mucinous neoplasms of the pancreas: a multicenter study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sijia Cui ◽  
Tianyu Tang ◽  
Qiuming Su ◽  
Yajie Wang ◽  
Zhenyu Shu ◽  
...  
Keyword(s):  
Calibration Curve ◽  
Main Pancreatic Duct ◽  
Validation Cohort ◽  
External Validation ◽  
High Grade ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Training Cohort ◽  
Independent Validation ◽  
Medical Centers ◽  
Mucinous Neoplasms

Abstract Background Accurate diagnosis of high-grade branching type intraductal papillary mucinous neoplasms (BD-IPMNs) is challenging in clinical setting. We aimed to construct and validate a nomogram combining clinical characteristics and radiomic features for the preoperative prediction of low and high-grade in BD-IPMNs. Methods Two hundred and two patients from three medical centers were enrolled. The high-grade BD-IPMN group comprised patients with high-grade dysplasia and invasive carcinoma in BD-IPMN (n = 50). The training cohort comprised patients from the first medical center (n = 103), and the external independent validation cohorts comprised patients from the second and third medical centers (n = 48 and 51). Within 3 months prior to surgery, all patients were subjected to magnetic resonance examination. The volume of interest was delineated on T1-weighted (T1-w) imaging, T2-weighted (T2-w) imaging, and contrast-enhanced T1-weighted (CET1-w) imaging, respectively, on each tumor slice. Quantitative image features were extracted using MITK software (G.E.). The Mann-Whitney U test or independent-sample t-test, and LASSO regression, were applied for data dimension reduction, after which a radiomic signature was constructed for grade assessment. Based on the training cohort, we developed a combined nomogram model incorporating clinical variables and the radiomic signature. Decision curve analysis (DCA), a receiver operating characteristic curve (ROC), a calibration curve, and the area under the ROC curve (AUC) were used to evaluate the utility of the constructed model based on the external independent validation cohorts. Results To predict tumor grade, we developed a nine-feature-combined radiomic signature. For the radiomic signature, the AUC values of high-grade disease were 0.836 in the training cohort, 0.811 in external validation cohort 1, and 0.822 in external validation cohort 2. The CA19–9 level and main pancreatic duct size were identified as independent parameters of high-grade of BD-IPMNs using multivariate logistic regression analysis. The CA19–9 level and main pancreatic duct size were then used to construct the radiomic nomogram. Using the radiomic nomogram, the high-grade disease-associated AUC values were 0.903 (training cohort), 0.884 (external validation cohort 1), and 0.876 (external validation cohort 2). The clinical utility of the developed nomogram was verified using the calibration curve and DCA. Conclusions The developed radiomic nomogram model could effectively distinguish high-grade patients with BD-IPMNs preoperatively. This preoperative identification might improve treatment methods and promote personalized therapy in patients with BD-IPMNs.

Serum Concentration of Reg IV in Patients with Colorectal Cancer: Overexpression and High Serum Levels of Reg IV Are Associated with Liver Metastasis

Oncology ◽  
2007 ◽  
Vol 72 (5-6) ◽  
pp. 371-380 ◽  
Author(s):  
Naohide Oue ◽  
Hiroki Kuniyasu ◽  
Tsuyoshi Noguchi ◽  
Kazuhiro Sentani ◽  
Masanori Ito ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Serum Concentration ◽  
Serum Levels ◽  
High Serum

scholarly journals Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Malte Simon ◽  
Sadaf S. Mughal ◽  
Peter Horak ◽  
Sebastian Uhrig ◽  
Jonas Buchloh ◽  
...  
Keyword(s):  
Immune Cell ◽  
Validation Cohort ◽  
Soft Tissue Sarcomas ◽  
Immune Cell Infiltration ◽  
Methylation Data ◽  
Tumor Infiltration ◽  
Mesenchymal Tumors ◽  
Independent Validation ◽  
Genomic Aberrations ◽  
Immune Cell Infiltrates

Abstract Background Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors for which response to immunotherapies is not well established. Therefore, it is important to risk-stratify and identify STS patients who will most likely benefit from these treatments. Results To reveal shared and distinct methylation signatures present in STS, we performed unsupervised deconvolution of DNA methylation data from the TCGA sarcoma and an independent validation cohort. We showed that leiomyosarcoma can be subclassified into three distinct methylation groups. More importantly, we identified a component associated with tumor-infiltrating leukocytes, which suggests varying degrees of immune cell infiltration in STS subtypes and an association with prognosis. We further investigated the genomic alterations that may influence tumor infiltration by leukocytes including RB1 loss in undifferentiated pleomorphic sarcomas and ELK3 amplification in dedifferentiated liposarcomas. Conclusions In summary, we have leveraged unsupervised methylation-based deconvolution to characterize the immune compartment and molecularly stratify subtypes in STS, which may benefit precision medicine in the future.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

scholarly journals CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal transition in colorectal cancer

2018 ◽  
Vol 7 (11) ◽  
pp. 5643-5654 ◽  
Author(s):  
Shujuan Ni ◽  
Fei Ren ◽  
Midie Xu ◽  
Cong Tan ◽  
Weiwei Weng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Poor Survival ◽  
Mesenchymal Transition

High serum uric acid concentration predicts poor survival in patients with breast cancer

2017 ◽  
Vol 473 ◽  
pp. 160-165 ◽  
Author(s):  
Cai-Feng Yue ◽  
Pin-Ning Feng ◽  
Zhen-Rong Yao ◽  
Xue-Gao Yu ◽  
Wen-bin Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Acid Concentration ◽  
High Serum ◽  
Uric Acid Concentration ◽  
Poor Survival ◽  
Serum Uric Acid Concentration

High Expression of sLex Associated with Poor Survival in Argentinian Colorectal Cancer Patients

2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Normal Mucosa ◽  
Poor Survival ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

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