Abundance of the Organic Anion-transporting Polypeptide OATP4A1 in Early-Stage Colorectal Cancer Patients

2019 ◽  
Vol 27 (3) ◽  
pp. 185-194 ◽  
Author(s):  
Veronika Buxhofer-Ausch ◽  
Maidah Sheikh ◽  
Christoph Ausch ◽  
Simone Zotter ◽  
Heike Bauer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Organic Anion ◽  
Organic Anion Transporting Polypeptide ◽  
Colorectal Cancer Patients

scholarly journals SLCO1B3 screening in colorectal cancer patients using High-Resolution Melting Analysis method and immunohistochemistry

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769117 ◽  
Author(s):  
Lampri Evangeli ◽  
Sainis Ioannis ◽  
Kounnis Valentinos ◽  
Mitselou Antigony ◽  
Ioachim Elli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Resolution ◽  
Cancer Patients ◽  
High Resolution Melting ◽  
Organic Anion ◽  
High Resolution Melting Analysis ◽  
Organic Anion Transporting Polypeptide ◽  
Melting Analysis ◽  
Colorectal Cancer Patients ◽  
Gene Alterations

Personalized medicine has made some major advances in colorectal cancer, but new biomarkers still remain a hot issue as an emerging tool with potential prognostic and therapeutic potential. We investigated for SLCO1B3 gene alterations and protein expression in colorectal cancer, using the novel high-resolution melting analysis technique and immunohistochemistry. Formalin-fixed paraffin-embedded tumor samples from 30 colorectal cancer patients were used. The screening for gene alterations was done by high-resolution melting analysis for all exons of SLCO1B3 gene. Organic anion-transporting polypeptide 1B3 protein expression was assessed by immunohistochemistry using the monoclonal mouse MDQ antibody. High level of polymorphism was observed in the SLCO1B3 gene. We identified three previously reported polymorphisms in exons 7, 12, and 14, 699G>A, 1557A>G, and 1833G>A, respectively. In the exon 5, one variant seems to correspond to an as yet unknown SLCO family member. The immunohistochemical study revealed that organic anion-transporting polypeptide 1B3 was expressed in 27/30 samples. Of great interest, the three samples, which were immunohistochemically negative, all appeared to accommodate mutations which lead to either early stop codons or other conformations of the tertiary protein structures affecting the antibody-epitope binding. The results of this study are of much interest as high-resolution melting analysis proved to be a reliable and rapid genotyping/scanning method for mutation detection of SLCO1B3 gene.

scholarly journals Novel genomic classifier for early stage colorectal cancer patients

2018 ◽  
Vol 29 ◽  
pp. viii33-viii34
Author(s):  
E. Letellier ◽  
M. Schmitz ◽  
A. Ginolhac ◽  
E. Koncina ◽  
M. Marchese ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Colorectal Cancer Patients

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3586-3586
Author(s):  
Jia Ke ◽  
Xuanhui Liu ◽  
Xiaofeng Jiang ◽  
Yufeng Chen ◽  
Zerong Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
Training Cohort ◽  
Immune Related Genes ◽  
Colorectal Cancer Patients ◽  
Disease Free

3586 Background: Immune-related genes (IRGs) were found to be associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of IRGs in predicting prognosis of early-stage CRC patients. Methods: According to the CIT microarray data set, 309 early-stage CRC patients were selected for generation of immune-related gene signature (IRGS). 5 independent data sets included 1587 CRC patients with complete prognostic information were divided into a training cohort (566 patients) and two validation cohorts (624 patients in validation-1 and 397 patients in meta-validation). Prognostic analysis were performed to test the predictive value of IRGS. Results: Of 309 early-stage CRC patients, a prognostic immune signature included 23 immune-related genes was constructed. In the training cohort, when considering patients with early tumor stage (I or II), IRGS significantly stratified patients into immune low- vs high-risk groups in terms of disease-free survival (HR = 5.03, 95%CI = 2.94-8.62, P < 0.001). Similarly, higher IRGS was correlated with significantly worse prognosis of early-stage CRC patients in validation-1 (HR = 2.71, 95%CI = 1.44-5.08, P = 0.001) and meta-validation cohort (HR = 3.10, 95%CI = 1.60-6.00, P < 0.001). When compared with Oncotype DX, we found IRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.85 vs 0.65) and the validation-1 cohort (mean C-index, 0.72 vs 0.61). After integrated with clinical characteristics, IRGS remained as an independent prognostic factor after adjusting for T stage and TNM stage of tumor in multivariate analysis (HR = 2.02, 95%CI = 1.61-2.53, P < 0.001). Furthermore, IRGS stratified immune low-risk group patients with adjuvant chemotherapy showed even worse disease-free survival when compared with those without adjuvant chemotherapy (HR = 5.66, 95%CI = 3.153-10.16, P < 0.001 in the training cohort and HR = 3.21, 95%CI = 1.74-5.92, P < 0.001 in the validation-1 cohort). IRGS identified immune high-risk group obtained a significantly higher immune and stromal infiltration (P < 0.001). Particularly, the percentages of Macrophages M2 and CD8+ T cells infiltration were significantly different between these two groups. Conclusions: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those in early-stage. Further studies are needed to evaluate the clinical utility of this system in predicting prognosis of colorectal cancer patients.

scholarly journals Increased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients

Cancer ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 4014-4022 ◽  
Author(s):  
Annemarie Boleij ◽  
Rian Roelofs ◽  
Renée M. J. Schaeps ◽  
Tanja Schülin ◽  
Philippe Glaser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Bacterial Antigen ◽  
Colorectal Cancer Patients

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients

2020 ◽  
Vol 46 (10) ◽  
pp. e62-e70 ◽  
Author(s):  
Jia Ke ◽  
Xuan-hui Liu ◽  
Xiao-feng Jiang ◽  
Zhen He ◽  
Jian Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Gene Signature ◽  
Related Gene ◽  
Immune Related Gene ◽  
Colorectal Cancer Patients

Pathway analysis of hypoxia-related factors in early colorectal cancer patients with poor prognosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3613-3613
Author(s):  
Yingxin Tan ◽  
Yuming Rong ◽  
Zhaoliang Yu ◽  
Feng Gao ◽  
Yufeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Validation Cohort ◽  
Early Stage ◽  
Microarray Dataset ◽  
Gene Signature ◽  
Stage I ◽  
Training Cohort ◽  
Cell Cycle Pathway ◽  
Colorectal Cancer Patients

3613 Background: Colorectal cancer is one of the most common malignancies with a high mortality rate. Patients with stage I and stage II colorectal cancer have limited options for treatment. Hypoxia affects the activation and regulation of colorectal cancer cells and participates in its invasion and migration. However, there is lack of an accurate and non-invasive method for assessing tumor hypoxia. The aim of this study was developing and validating a hypoxia gene signature for predicting the outcome in stage I/II colorectal cancer patients. At the same time , we hypothesized that analysis of database of CIT microarray dataset could identify important biomarkers for stage I/II colorectal cancer patients. Methods: A total of 309 colorectal cancer patients of early stage with complete clinical information were enrolled for construction generation of hypoxia-related gene signature (HRGS) based on the CIT microarray dataset. 1877 colorectal cancer patients with complete prognostic information in 5 independent datasets were divided into a training cohort and two validation cohort (TCGA and meta-validation). Prognostic analysis was assessed in these cohort to evaluate the predictive value of HRGS. Results: A model of prognostic HRGS containing 14 hypoxia-related genes was developed. In training cohort and two validation cohorts, patients in hypoxia high-risk group satisfied by our HRGS had significant poor disease free survival compared with those in the in the low risk group (HR=4.35, 95% CI=2.30-8.23, P<0.001 in training cohort, HR=2.14, 95% CI=1.09-4.21, P=0.024 in TCGA cohort, HR=1.91, 95% CI=1.08-3.39, P=0.024 in meta-validation cohort). When compared with Oncotype DX, HRGS achieved an improved survival correlation in the training cohort (mean C-index, 0.80 vs 0.65, P<0.05) and the validation cohort (mean C-index, 0.70 vs 0.61 in the TCGA cohort, mean C-index, 0.68 vs 0.73 in the meta-validation cohort). Analysis of the data found that patients with low survival rates have significant relationships with genes regulated by the cell cycle pathway, such as mTROC1, E2F, G2-M, mitotic, oxidative phosphorylation, MYC, PI3K-AKT-mTOR (P<0.005). Conclusions: HRGS was a satisfactory prognostic prediction model for early stage colorectal patients. Hypoxia-related genes that regulate the cell cycle pathway were associated with prognosis in patients with stage I and stage II colorectal cancer. Further researches are needed to assess the clinical effectiveness of the system and the treatment options for biological targets.

scholarly journals EGFR pathway subgroups in Chilean colorectal cancer patients, detected by mutational and expression profiles, associated to different clinicopathological features

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831772451 ◽  
Author(s):  
Karin Alvarez ◽  
Paulina Orellana ◽  
Cynthia Villarroel ◽  
Luis Contreras ◽  
Hiroshi Kawachi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Expression Profiles ◽  
Kras Mutations ◽  
Variable Expression ◽  
Molecular Features ◽  
Egfr Expression ◽  
Pten Deletion ◽  
Colorectal Cancer Patients

Colorectal cancer is a multistep process affecting several signaling pathways including EGFR (epidermal growth factor receptor), a therapeutic target for metastatic disease. Our aim was to characterize the mutational and expression profiles of the EGFR pathway in colorectal tumors and to integrate these results according to five previously defined groups. We screened seven genes for mutations ( KRAS-BRAF-PIK3CA-PIK3R1-AKT1-MAP2K1-PTEN) and six proteins (EGFR-p110α-p85α-PTEN-phosphoAKT-phosphoMEK1) by immunohistochemistry, PTEN deletion, and MSI. At least one mutated gene was observed in 68% of tumors ( KRAS 45%, PIK3CA 21%, BRAF 14%, and PTEN 7%). PTEN deletion was observed in 10.7% of tumors and 19.6% were MSI-High. In all, 54% of tumors showed a high EGFR expression, 48% p110α, 4.4% phosphoAKT, and 22% phosphoMEK1; and 43% showed low PTEN expression and 22% p85α. In total, five groups of tumors were defined based on MSI, BRAF, and KRAS mutations. Three groups gather mainly early-stage tumors, whereas a fourth group is mostly conformed by advanced tumors. We described here that 71.4% of tumors from one group have a mutated PI3K/PTEN pathway, in comparison to other groups having 32%, 27%, and 25%. In addition, the five groups are differentiated by molecular features such as EGFR, p85α, p110α, and PTEN, showing variable expression among tumor groups. In conclusion, alterations on the EGFR pathway were found in a high percentage of colorectal cancer patients. Using the integration of diverse molecular markers, we ratified previous classification in an ethnic group having relevant genetic differences and living in a different environmental background, adding complementary molecular targets related to therapy.

scholarly journals Urine Metabolite Profiling of Human Colorectal Cancer by Capillary Electrophoresis Mass Spectrometry Based on MRB

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jin-Lian Chen ◽  
Jing Fan ◽  
Liu-Shui Yan ◽  
Hui-Qin Guo ◽  
Jing-Jing Xiong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mass Spectrometry ◽  
Capillary Electrophoresis ◽  
Cancer Patients ◽  
Advanced Colorectal Cancer ◽  
Early Stage ◽  
Urine Samples ◽  
Urine Metabolites ◽  
Colorectal Cancer Patients ◽  
Capillary Electrophoresis Mass Spectrometry

Aim. The study was to investigate the metabolic profile of urine metabolites and to elucidate their clinical significance in patients with colorectal cancer.Methods. Colorectal cancers from early stage and advanced stage were used in this study. Urine samples of colorectal cancer patients and healthy adults were collected and subjected to capillary electrophoresis mass spectrometry based on moving reaction boundary analysis. The metabolic data were analyzed by SPSS 17.0 to find urinary biomarkers for colorectal cancer.Results. The results indicated that the urine metabolic profiling of colorectal cancer patients had significant changes compared with the normal controls, and there were also differences between early stage and advanced colorectal cancer patients. Compared with the control group, the levels of isoleucine, valine, arginine, lactate acid and leucine increased(P<0.05), but those of histidine, methionine, serine, aspartic acid, citric acid, succinate, and malic acid decreased in urine samples from colorectal cancer(P<0.05). Furthermore, the levels of isoleucine and valine were lower in urine of patients with advanced colorectal cancer than those in early stage colorectal cancer(P<0.05).Conclusion. The technique of capillary electrophoresis mass spectrometry based on MRB could reveal the significant metabolic alterations during progression of colorectal cancer, and the method is feasible and may be useful for the early diagnosis of colorectal cancer.

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