Epithelial mesenchymal transition in an advanced BRAF mutation type colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 693-693
Author(s):  
Jun-Eul Hwang ◽  
Woo Kyun Bae ◽  
Hyun-Jeong Shim ◽  
Sang-Hee Cho ◽  
Ik-Joo Chung
Keyword(s):  
Colorectal Cancer ◽  
Braf Mutation ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Disease Free ◽  
Mutation Type

693 Background: BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer. Methods: A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in three independent cohorts (GSE 17536, GSE 14333, and GSE 39582). Results: The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation type colorectal cancer was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.0355), poor disease-free survival (P = 0.00794), and poor disease-specific survival (P = 0.0341) in GSE 17536. In GSE 39582, BRAF mutation type colorectal cancer demonstrated the trend of poor overall survival according to increase of stage. In a multivariate analysis, BRAF mutation gene signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.7; 95% CI 1.59-2.83: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition and colon cancer metastasis signaling are the possible explanations for poor prognosis of BRAF mutation type colorectal cancer. Conclusions: BRAF mutation signature is highly associated with poor prognosis in colorectal cancer, especially in advanced stage, and the molecules associated with epithelial-mesenchymal transition can be potential therapeutic targets in BRAF mutation type colorectal cancer.

scholarly journals Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

scholarly journals An Elevated Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Colorectal Cancer: A Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xuan-zhang Huang ◽  
Wen-jun Chen ◽  
Xi Zhang ◽  
Cong-cong Wu ◽  
Chao-ying Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Platelet To Lymphocyte Ratio ◽  
Poor Overall Survival ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Lymphocyte Ratio

Background.The aims of this study were to evaluate the clinicopathological and prognostic values of platelet-to-lymphocyte ratio (PLR) in colorectal cancer (CRC).Methods.The PubMed and Embase databases and the references of relevant studies were systematically searched. This study was performed with hazard ratios (HRs) and odd ratios (ORs) with corresponding 95% confidence intervals (CIs) as effect measures.Results.Our results indicated that elevated PLR was associated with poor overall survival (HR = 1.46, 95% CI = 1.23–1.73), disease-free survival (HR = 1.64, 95% CI = 1.17–2.30), cancer-specific survival (HR = 1.30, 95% CI = 1.12–1.51), and recurrence-free survival (HR = 1.38, 95% CI = 1.09–1.74) in CRC. For the clinicopathological characteristics, our results indicated that there were differences in the rate of elevated PLR between stages III/IV and I/II groups (OR = 1.38, 95% CI = 1.01–1.88), pT3/T4 and pT1/T2 groups (OR = 1.82, 95% CI = 1.03–3.20), and poor differentiation and moderate/well differentiation (OR = 2.59, 95% CI = 1.38–4.84).Conclusions.Our results indicated that elevated PLR predicted poor prognosis and clinicopathological characteristics in CRC and PLR is a convenient and low-cost blood-derived prognostic marker for CRC.

scholarly journals Methylation changes in the TFAP2E promoter region are associated with BRAF mutation and poorer overall & disease free survival in colorectal cancer

Oncoscience ◽  
2015 ◽  
Vol 2 (5) ◽  
pp. 508-516 ◽  
Author(s):  
Andrew D. Beggs ◽  
Mark P. Dilworth ◽  
Enric Domingo ◽  
Rachel Midgley ◽  
David Kerr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Braf Mutation ◽  
Promoter Region ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Huabin Gao ◽  
Jiangtao Liang ◽  
Jing Duan ◽  
Lin Chen ◽  
Hui Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
High Expression ◽  
Transmembrane Transport ◽  
Classical Pathway ◽  
Mrna Levels ◽  
Poor Overall Survival ◽  
Mesenchymal Transition

SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

Establishing Adrenocortical Carcinoma Specific Prognostic Genes Signature

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S148-S149
Author(s):  
A R Patil ◽  
D S Dabrowski ◽  
J Cotelingam ◽  
D Veillon ◽  
M Ong ◽  
...  
Keyword(s):  
Median Survival ◽  
Poor Prognosis ◽  
Cancer Genomics ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Malignant Neoplasms ◽  
Free Survival ◽  
Signature Genes ◽  
Disease Free ◽  
Disease Specific

Abstract Introduction/Objective Adrenal Cortical Carcinoma (ACC) is a rare malignant neoplasms originating from adrenal cortical tissue with an annual incidence rate of 1 to 2 cases per million individuals. These tumors have poor prognosis with 5-year disease free survival being 30% after complete resection in Stage I to Stage III patients. Hence, there is a need for identifying prognostic markers for effective management of disease in these patients. Methods We analyzed the data in The Cancer Genome Atlas of 1141 ACC individuals, using cbioportal.org, a web- based platform for analysis of large-scale cancer genomics data sets, and derived correlation between prognosis and genetic alterations in approximately 51,309 genes. Results We identified 15 signature genes (NOTCH1, TP53, ZNRF3, LRP1, KIF5A, MDM2, LETMD1, MTOR, NOTCH3, RERE, SMARCC2, LDLR, HRNR, AVPR1A and PCDH15), alterations in which indicated a poor prognosis for ACC individuals. Analysis of 15 signature genes demonstrated that disease specific median survival for the patients with ACC, was reduced to 39.5 months (p value &lt; 8 x 10 -9 and sensitivity of 93%) when any one or more of these genes was altered. Whereas, disease specific median survival was greater than 180 months (90% survival being 180 months) with no alteration in our signature genes. In addition, our analysis of our signature genes demonstrates reduced overall survival, disease free survival and progression free survival in individuals having alterations in our signature genes. Moreover, our set of 15 genes belonged mainly to MDM2-TP53, NOTCH and mTOR pathways, and small molecule modulators of these pathways are in process of development. Conclusion Our 15 gene signature was not only able to predict poor prognosis in ACC, but also has the potential to serve as a molecular marker set for initiation of NOTCH and mTOR specific targeted therapies in these patients.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

scholarly journals Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yaodu Wang ◽  
Zhiyang Wu ◽  
Likuan Hu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Multivariate Regression Analysis ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Patients With Diabetes ◽  
E Cadherin

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.

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