Quantitative expression analysis and prognostic significance of the novel apoptosis-related gene BCL2L12 in colon cancer

2008 ◽  
Vol 389 (12) ◽  
Author(s):  
Christos K. Kontos ◽  
Iordanis N. Papadopoulos ◽  
Andreas Scorilas
Keyword(s):  
Colon Cancer ◽  
Early Stage ◽  
Critical Role ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Housekeeping Gene ◽  
Colon Tissue ◽  
Quantitative Expression ◽  
Quantification Analysis ◽  
Well Differentiated

Abstract Apoptosis is a tightly regulated process that plays a critical role in many biological events. Members of the BCL2 (Bcl-2) family of apoptosis-related genes have been found to be differentially expressed in various malignancies and have been proposed as prognostic tumor biomarkers. We have recently discovered and cloned a new member of the BCL2 gene family, BCL2L12, expressed in colon tissues. Here we have investigated expression of the BCL2L12 gene in colon cancer tissues and assessed its prognostic value. Total RNA was isolated from 96 specimens of malignant colon tissue. After testing the RNA quality, cDNA was prepared by reverse transcription. A highly sensitive real-time PCR method for BCL2L12 mRNA quantification was developed using SYBR® Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method (2-ΔΔCT). High BCL2L12 expression levels were found in smaller (≤5 cm, p=0.027) and well-differentiated tumors (p=0.034), as well as in early-stage tumors (p=0.039). Survival analysis demonstrated that patients with BCL2L12-positive colon tumors have significantly longer disease-free survival and overall survival (p=0.015 and p=0.027, respectively). Our results suggest that BCL2L12 gene expression may represent a potential new biomarker for colon cancer.

Systematic review of adjuvant therapy for early stage (epithelial) ovarian cancer

2003 ◽  
Vol 13 (4) ◽  
pp. 395-404 ◽  
Author(s):  
B. Winter-Roach ◽  
L. Hooper ◽  
H. Kitchener
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Difference ◽  
Well Differentiated ◽  
Platinum Chemotherapy

A systematic review and meta analysis has been undertaken in order to evaluate the effectiveness of adjuvant therapy following surgery for early ovarian cancer. Trials reported since 1990 have been of a higher quality enabling a meta analysis of adjuvant chemotherapy vs adjuvant radiotherapy and a meta analysis of adjuvant chemotherapy vs observation. There was no significant difference between radiotherapy and chemotherapy, though these comprised studies which demonstrated considerable heterogeneity. Chemotherapy did confer significant benefit over observation in terms of both overall and disease free survival. Except for women in whom adequate surgical staging has revealed well differentiated disease confined to one or both ovaries with intact capsule, platinum chemotherapy should be offered to reduce risk of recurrence.

scholarly journals The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-Stage Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhi-Yuan Chen ◽  
Zhi-Xing Guo ◽  
Liang-He Lu ◽  
Jie Mei ◽  
Wen-Ping Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Value ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Treatment Optimization ◽  
Initial Hepatectomy ◽  
Significant Difference

Abstract Background. The vessels encapsulating tumor clusters (VETC) pattern is an effective predictor of survival in patients with hepatocellular carcinoma (HCC) after resection. The predictive value of VETC in recurrent early-stage HCC remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods. From December 2005 to December 2016, 138 patients who underwent RHR and 188 patients who underwent RFA were enrolled. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of treatment for patients with or without the VETC pattern was investigated. Results. Among VETC-positive HCC patients, 50 patients underwent RHR, and 69 patients underwent RFA; among VETC-negative HCC patients, 88 patients underwent RHR, and 119 patients underwent RFA. There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group had a longer median DFS time compared to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group had a longer median OS time compared to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, there was no significant difference in DFS and OS rates between the RHR and RFA groups (P>0.05).Conclusions. The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

Expression analysis and study of KLK4 in benign and malignant breast tumours

2009 ◽  
Vol 101 (02) ◽  
pp. 381-387 ◽  
Author(s):  
Georgia Papachristopoulou ◽  
Margaritis Avgeris ◽  
Andreas Scorilas
Keyword(s):  
Expression Analysis ◽  
Housekeeping Gene ◽  
Mrna Levels ◽  
Breast Tumours ◽  
Potential Biomarker ◽  
Quantification Analysis ◽  
Malignant Breast ◽  
Well Differentiated ◽  
Tissue Specimens ◽  
Analysis And Study

SummaryThe steroid hormone-regulated gene KLK4 (kallikrein 4) is a new member of the human kallikrein-related peptidase gene family. Up to date, studies report that KLK4 is differentially expressed in many tumours. The purpose of this study was the expression analysis and study of KLK4 in benign and malignant breast tumours. Total RNA was isolated from 16 benign and 45 malignant breast tissue specimens. After testing RNA quality, cDNA was prepared by reverse transcription. Highly sensitive quantitative real-time PCR method for KLK4 mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method 2-ΔΔCT. KLK4 expression was found to vary in both patients’ cohorts; however, a statistically significant elevation of the KLK4 mRNA levels was observed in malignant compared to benign tumour patients. Low KLK4 expression levels were found in well-differentiated tumours (p=0.011) as well as in stage I (p=0.024) patients. Moreover, a statistically significant (rs=-0.318, p=0.035) negative correlation between the KLK4 expression and progesterone receptor staining was observed. ROC and logistic regression analysis recommended that KLK4 gene expression may be used as a new potential biomarker in breast cancer.

scholarly journals Non-digestible fraction of beans (Phaseolus vulgarisL.) modulates signalling pathway genes at an early stage of colon cancer in Sprague–Dawley rats

2012 ◽  
Vol 108 (S1) ◽  
pp. S145-S154 ◽  
Author(s):  
Vergara-Castañeda Haydé ◽  
Guevara-González Ramón ◽  
Guevara-Olvera Lorenzo ◽  
Oomah B. Dave ◽  
Reynoso-Camacho Rosalía ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Common Bean ◽  
Early Stage ◽  
Expression Profiles ◽  
Signalling Pathway ◽  
Colorectal Adenomas ◽  
Major Public Health Problem ◽  
Colon Tissue ◽  
Inhibition Of Proliferation

Colorectal cancer is one of the most common causes of morbidity and mortality in Western countries, the second cause of cancer mortality in the USA and a major public health problem in Mexico. A diet rich in legumes is directly related to the prevention of colon cancer, showing an inverse relationship with the development of colorectal adenomas in human subjects. The present study shows the results of molecular changes involved in theTp53pathway at an early stage in the distal colon tissue of azoxymethane (AOM)-induced colon cancer in rats evaluated by PCR array after exposure to diets containing the non-digestible fraction (NDF) of cooked bean (cultivar Bayo Madero). Significant differences were detected in seventy-two genes of theTp53-mediated signalling pathway involved in apoptosis, cell-cycle regulation and arrest, inhibition of proliferation and inflammation, and DNA repair.Tp53,Gadd45a,Cdkn1aandBaxwere highly expressed (9·3-, 18·3-, 5·5- and 3·5-fold, respectively) in the NDF+AOM group, whereasCdc25c,Ccne2,E2f1andBcl2were significantly suppressed ( − 9·2-, − 2·6-, − 18·4- and − 3·5-fold, respectively), among other genes, compared with the AOM group, suggesting that chemoprevention of aberrant crypt foci results from a combination of cell-cycle arrest in G1/S and G2/M phases and cell death by apoptotic induction. We demonstrate that the NDF from common bean modulates gene expression profiles in the colon tissue of AOM-induced rats, contributing to the chemoprotective effect of common bean on early-stage colon cancer.

scholarly journals Low levels of BRCA1 protein expression predict a worse prognosis in stage I–II colon cancer

2021 ◽  
pp. 172460082098657
Author(s):  
Changzheng Du ◽  
Yifan Peng ◽  
Yiping He ◽  
Guoan Chen ◽  
Hao Chen
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Disease Free Survival ◽  
Brca1 And Brca2 ◽  
Brca1 Protein ◽  
Free Survival ◽  
Expression Levels ◽  
Low Levels ◽  
Disease Free

Background: BRCA1 and BRCA2 have been well studied for their roles in tumorigeneis, plus cancer diagnosis and treatment, but their prognostic value in colon cancer, especially for early-stage cancer, has not been fully illuminated. This study examined the expression levels of BRCA1 and BRCA2 proteins in sporadic colon cancer cases and investigated their value in prognosis. Methods: The expression levels of BRCA1 and BRCA2 in 275 colon cancer patients who underwent radical surgeries were assayed by immunohistochemical staining in dissected tumor samples. Also, its correlation with clinicopathological characteristics, disease-free survival, and overall survival was investigated. Results: Tumors with low expression levels of BRCA1, BRCA2, and both were 19.6%, 17.8%, and 6.5%, respectively. The levels of BRCA1/2 expression were not associated with clinicopathological parameters (gender, age, histological differentiation, and tumor node metastasis stage). Patients with low-levels of BRCA1 protein in their tumors demonstrated a lower chance of 5-year disease-free survival (55.6% vs. 69.7%, P=0.046), which was more obvious in the patients with stage I–II tumors without chemotherapy (52.6% vs. 82.6%, P=0.006). Neither BRCA1 nor BRCA2 affected overall survival in this cohort. Multivariate analysis revealed that pathologic stage and the level of BRCA1 protein were independent factors of long-term disease-free survival. Conclusion: This study highlights BRCA1 as an independent prognosticator of early-stage colon cancer.

A prospective study of prognostic role of plasma circulating tumor DNA (ctDNA) in patients (pts) with early-stage malignancies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3559-3559
Author(s):  
Mikhail Fedyanin ◽  
Uljana Boyarskikh ◽  
Elizaveta Polyanskaya ◽  
Vechaslav Aliev ◽  
Zaman Mamedli ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Median Time ◽  
Cancer Progression ◽  
Somatic Mutations ◽  
Cox Regression ◽  
Early Stage ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Sample Collection ◽  
General Group

3559 Background: Recently, conflicting evidence has emerged showing the association of ctDNA level and cancer progression. The aim of our study was the development of a method for detecting ctDNA in plasma and the investigation of the prognostic value of ctDNA retention after surgery in the prospective way. Methods: This prospective, single-center, sample collection study; pts with early-stage malignancies of the different origin were included. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored in plasma samples taken before and after surgery. The median time between surgery and plasma collection was 7 days (5-15). Mutations of plasma ctDNA were determined by ddPCR. The plasma sample was considered "positive" if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma. We needed 265 pts for improving 1-year disease free survival (DFS) from 60% to 80% with α=0.01, β=0.1, 10% loss of f.-up and duration of the study for 2 years. Results: The study comprised 271 pts with various cancers including colorectal – 91 (33,6%), pancreatic – 37 (13,7%), breast – 66 (24,4%), lung – 35 (12,9%) and gastric cancer – 42 (15,5%). Pts with stage I was 50 (18,5%), stage II – 118 (43,5%) and stage III – 103 (38%). The median time of the f.-up was 9 mos. (1-37). No significant association was found between the level of ctDNA before surgery and DFS either in the general group or in groups stratified by tumor sites (HR 2.4, 95%CI 0.8-7.1, р=0.12 and HR 1.5, 95%CI 0.4-6.3, р=0.5, correspondingly). ctDNA was detected in the plasma after surgery in 57 (10%) pts: 9 (9.9%) cases of colorectal, 10 (27%) - pancreatic, 9 (13.6%) - breast, 19 (54.3%) - lung, and 10 (23.8%) - gastric cancer. Progression of the disease was detected in 28/57 (49%) pts with ctDNA(+) and 17/214 (8%) - in ctDNA(-) pts (p<0.001). One-year DFS in ctDNA(+) and ctDNA(-) pts were 57% and 87%, respectively (HR 6.1, 95%CI 3.3-11.2, p<0,001). ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 5.7, 95%CI 3.1-10.8, p <0.001). Conclusions: These results demonstrate the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the different malignancies. Further clinical validation of this approach is required in trails with modifications of the adjuvant treatment, according to the content of ctDNA.

scholarly journals Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study

ESMO Open ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. e000638 ◽  
Author(s):  
David Lau ◽  
Eleftheria Kalaitzaki ◽  
David N Church ◽  
Hardev Pandha ◽  
Ian Tomlinson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mismatch Repair ◽  
Early Stage ◽  
Randomised Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Colon Cancers ◽  
Exonuclease Domain ◽  
The Uk

Background10%–15% of early-stage colon cancers harbour either deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or POLE exonuclease domain mutations, and are characterised by high tumour mutational burden and increased lymphocytic infiltrate. Metastatic dMMR colon cancers are highly sensitive to immune checkpoint inhibition, and recent data show POLE-mutant tumours are similarly responsive. We are conducting a phase III randomised trial to determine if the addition of the anti-PD-L1 antibody avelumab following adjuvant chemotherapy improves disease-free survival (DFS) in patients with stage III dMMR/MSI-H or POLE mutant colon cancer and is a cost-effective approach for the UK National Health Service (NHS).MethodsWe are recruiting patients with completely resected, stage III colon cancer confirmed to have dMMR/MSI-H, locally or POLE exonuclease domain mutation on central testing. Eligible patients are randomised in a 1:1 ratio to standard fluoropyrimidine-based chemotherapy (capecitabine, oxaliplatin for 12 weeks or capecitabine for 24 weeks) or chemotherapy, followed by avelumab (10 mg/kg, 2 weekly for 24 weeks). Stratification is by chemotherapy received and MMR/MSI-H status. The primary endpoint is DFS. Secondary endpoints include overall survival, toxicity, quality of life and health resource use. The 3-year DFS rate in the control arm is expected to be ~75%. Avelumab is expected to improve the 3-year DFS rate by 12% (ie, 87%). Target accrual is 402 patients, which provides 80% power to detect an HR of 0.48 for DFS at a two-sided alpha of 0.05. This national, multicentre phase III trial is sponsored by the Royal Marsden NHS Foundation Trust and it is anticipated that approximately 40 centres in the UK will participate. This study opened to recruitment in August 2018.Trial registration numberNCT03827044

scholarly journals Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3β pathway

2019 ◽  
Vol 41 (8) ◽  
pp. 1123-1133 ◽  
Author(s):  
Bo Gao ◽  
Lianmei Zhao ◽  
Feifei Wang ◽  
Hanyu Bai ◽  
Jing Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Critical Role ◽  
Disease Free Survival ◽  
Clinical Samples ◽  
Colon Cancer Cells ◽  
And Migration ◽  
Gsk 3Β ◽  
Proliferation And Migration

Abstract Isochorismatase domain-containing 1 (ISOC1) is a coding gene that contains an isochorismatase domain. The precise functions of ISOC1 in humans have not been clarified; however, studies have speculated that it may be involved in unknown metabolic pathways. Currently, it is reported that ISOC1 is associated with breast cancer. In this research, the aim is to investigate the critical role of ISOC1 in colorectal cancer (CRC) and to explore its biological function and mechanism in colon cancer cells. In 106 paired clinical samples, we found that the levels of ISOC1 expression were widely increased in cancer tissues compared with matched adjacent non-tumor tissues and that increased expression of ISOC1 was significantly associated with tumor size, tumor invasion, local lymph node metastasis and Tumor, Node and Metastasis (TNM) stage. Moreover, higher expression levels of ISOC1 were correlated with shorter disease-free survival in patients 2 years after surgery. In vitro, ISOC1 knockdown inhibited the proliferation and migration and induced the apoptosis of colon cancer cells, and in vivo, the xenograft tumors were also inhibited by ISOC1 silencing. We also used MTS, Transwell and cell apoptosis assays to confirm that ISOC1 plays a critical role in regulating the biological functions of colon cancer cells through the AKT/GSK-3β pathway. Additionally, the results of confocal microscopy and western blot analysis indicated that ISOC1 knockdown could promote p-STAT1 translocation to the nucleus.

scholarly journals PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1943
Author(s):  
Pablo Azcue ◽  
Ignacio Encío ◽  
David Guerrero Setas ◽  
Javier Suarez Alecha ◽  
Arkaitz Galbete ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Molecular Subtype ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Stage Ii ◽  
Primary Endpoints ◽  
Early Stage Colon Cancer ◽  
Consensus Molecular Subtype

Background. There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. Methods. Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results. PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26–0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). Conclusions. Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.

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