scholarly journals Diagnostic and Prognostic Value of B4GALT1 Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1598 ◽  
Author(s):  
Francesco Picardo ◽  
Antonella Romanelli ◽  
Laura Muinelo-Romay ◽  
Tommaso Mazza ◽  
Caterina Fusilli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lung Metastases ◽  
Methylation Status ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Aberrant Expression ◽  
Predictive Values ◽  
Methylation Specific Pcr ◽  
Specific Pcr

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan–Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592–0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC.

Response to PD-1 and PD-L1 based immunotherapy in MSS advanced colorectal cancer is impacted by metastatic disease sites.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 72-72
Author(s):  
Marwan Fakih ◽  
Jaideep Singh Sandhu ◽  
Chongkai Wang ◽  
Ching Ouyang
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Disease Control ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Lung Metastases ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Liver Involvement ◽  
The Impact

72 Background: Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) has been associated with immunotherapy resistance. However, the impact of metastatic diseases sites on clinical outcome with checkpoint inhibition has not be adequately investigated. Methods: Following IRB approval (14361), we performed a retrospective study to assess the response and progression-free survival (PFS) to PD-1 or PD-L1 based therapy in patients with MSS mCRC who progressed following standard chemotherapy and targeted therapy. Patients were included if they received an FDA approved anti-PD1 or anti-PD-L1 agent, alone or in combination with other investigational agents. Exclusion criteria included concurrent cytotoxic therapy. Response and PFS were determined by RECIST guidelines. Results: 97 patients with refractory MSS mCRC satisfied the inclusion criteria were evaluable for analysis. 57, 17, 13, and 10 received nivolumab, atezolizumab, pembrolizumab, and durvalumab, respectively. 47, 8, 10, 10, 17 received concurrent VEGFR, MEK, CTLA-4, radiation, or other targeted therapies. Among tested variables, including age, gender, primary tumor location, ECOG status, RAS, BRAF, APC, TP53, TMB, and sites of metastasis, only ECOG status (0 vs. 1) and metastatic disease to the liver were associated with disease control (partial response and stable disease; p = 0.005 and < 0.001 respectively). Disease control rates in patients without liver metastases (n = 43) was 56% (95% CI: 40-71%), compared with 2% (95% CI: 0.1-10%) in patients with liver metastases (n = 54) (p < 0.001). Also, liver involvement was predictive for PFS based on multivariate Cox regression model (p < 0.001). The median PFS in patients with liver involvement was 1.5 vs 4.5 months for no liver involvement (HR = 4.41, p = < 0.001). Amongst patients without liver metastases, 35% (15/43) remained without progression at 6 months. These patients were characterized by lung metastases (n = 8) and/or lymph node metastases (n = 4). Conclusions: The presence of liver metastases is MSS mCRC is predictive for lack of benefit from PD-1/PD-L1 inhibitors. Patients without liver metastases can derive a meaningful clinical benefit, with 35% being progression-free at 6 months. Future PD-1/PD-L1 drug development should consider metastatic sites of disease in study design and development.

Promotor Demethylation as a Mechanism of HOX11 Activation in Adult T-ALL?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2288-2288
Author(s):  
Ulrike Baak ◽  
Helmut Orawa ◽  
Nicola Goekbuget ◽  
Olaf Hopfer ◽  
Thomas Burmeister ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Cytosine Methylation ◽  
Methylation Status ◽  
Cpg Methylation ◽  
Methylation Array ◽  
Aberrant Expression ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Significant Difference

Abstract Promotor demethylation of oncogenes has been associated with transcriptional activation in cancer cells. The proto-oncogene HOX11/TLX1 has been found to be aberrantly expressed in up to 30% of adult T-ALL patients. In few, a translocation between the HOX11 locus at 10q24 and the T-cell receptor locus has been identified. In the majority of cases the mechanism leading to HOX11 reactivation remains unclear. It had been proposed that an epigenetical modification by demethylation of the proximal HOX11 promotor could be responsible for an aberrant expression of HOX11. To test this hypothesis we have correlated the methylation status of CpG residues in the proximal HOX11 promotor with the gene expression status of HOX11 in adult T-ALL samples from the German Multicenter ALL Study (GMALL) 5/93 and 6/99. HOX11 expression was measured in 286 pretreatment peripheral blood and bone marrow blasts by comparative real-time RT-PCR as described previously. The methylation status was then randomly analyzed after bisulphite treatment by methylation-specific PCR (MSP) in 53 T-ALL samples with HOX11 expression (HOX11 positive) and 102 samples without HOX11 expression (HOX11 negative). Of the 150 analyzed patients only 4% of HOX11 positive patients (n=53) and 10% of HOX11 negative patients were methylated (M) in the analyzed promotor area. HOX11 negative patients were significantly more common associated with an unmethylated status (U) then HOX11 positive patients (57% vs 32%, p=0.003). The most prominent methylation phenotype in HOX11 positive patients compared to HOX11 negative samples was a mixed (MU) methylation status (55% vs. 27%, p=0.001). Interestingly, remission duration was significantly higher in pt. with the MU methylation status (M=49%, U=54% vs. MU=76%, p-logrank=0.0362). This translated also into a significant difference in the overall survival (M=55%, U=49%, MU=75%, p-logrank= 0.0202). However, in a multivariate analysis the methylation status could not be confirmed as an independent prognostic factor. The promotor-associated CpG methylation status was found to be remarkably heterogenous in the analyzed adult T-ALL patients with a predominantly unmethylated status in HOX11 negative samples and a mixed methylated/unmethylated picture in HOX11 positive samples. These findings contrast with our initial hypothesis that HOX11 expression is silenced in normal tissue by a promotor-associated CpG methylation and aberrantly reexpressed in leukemia cells by demethylation. However, various CpG residues associated with the HOX11 promotor might be of variable importance for the gene expression and intrinsic limitations of methylation-specific PCR might have influenced our analysis. Bisulphite sequencing techniques as well as the newly developed genome-wide cytosine methylation array could help overcome these issues. Understanding the role of promotor-associated methylation in HOX11 expression could clarify pathways in leukemogenesis and provide a valuable tool for better risk stratification in T-ALL.

SUV39H1-Mediated DNMT1 is Participated in the Epigenetic Regulation of Smad3 in Cervical Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Li Zhang ◽  
Sijuan Tian ◽  
Minyi Zhao ◽  
Ting Yang ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Promoter Region ◽  
Methylation Status ◽  
Regulation Mechanism ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Immune Factor ◽  
Cancer Tissues

Background: Smad3 is a pivotal intracellular mediator for participating in the activation of multiple immune signal pathway. Objective: The epigenetic regulation mechanism of the positive immune factor Smad3 in cervical cancer remains unknown. Therefore, the epigenetic regulation on Smad3 is investigated in this study. Methods: The methylation status of SMAD3 was detected by Methylation-specific PCR (MS-PCR) and Quantitative Methylation-specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of SUV39H1-DNMT1-Smad3 regulation was elucidated using cervical cancer cell lines containing siRNA or/and overexpression system. Confirmation of the regulation of DNMT1 by SUV39H1 used Chromatin immunoprecipitation-qPCR (ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t tests and one-way ANOVAs. Results: H3K9me3 protein which regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate its expression in cervical cancer cells, resulting in the reduce expression of the downstream target gene DNMT1. In addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The depletion of DNMT1 effectively restores the expression of Smad3 in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1-DNMT1 was found to correlate with Smad3 expression in accordance with the expression at the cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this hypermethylation inhibits the subsequent gene expression. Conclusion: These results indicate that SUV39H1-DNMT1 is a crucial Smad3 regulatory axis in cervical cancer. SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 108-108
Author(s):  
Benjamin Adam Weinberg ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Tim Maughan ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Wild Type ◽  
Cox Models ◽  
Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

scholarly journals Multiplexed DNA Methylation Analysis in Colorectal Cancer Using Liquid Biopsy and Its Diagnostic and Predictive Value

2021 ◽  
Vol 43 (3) ◽  
pp. 1419-1435
Author(s):  
Walter Pulverer ◽  
Kristi Kruusmaa ◽  
Silvia Schönthaler ◽  
Jasmin Huber ◽  
Marko Bitenc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Therapy Monitoring ◽  
Methylation Status ◽  
Methylation Analysis ◽  
Microarray Experiments ◽  
Specific Pcr ◽  
Colonic Adenomas ◽  
Methylation Sensitive Restriction Enzyme ◽  
Dna Methylation Analysis

Early diagnosis of colorectal cancer (CRC) is of high importance as prognosis depends on tumour stage at the time of diagnosis. Detection of tumour-specific DNA methylation marks in cfDNA has several advantages over other approaches and has great potential for solving diagnostic needs. We report here the identification of DNA methylation biomarkers for CRC and give insights in our methylation-sensitive restriction enzyme coupled qPCR (MSRE-qPCR) system. Targeted microarrays were used to investigate the DNA methylation status of 360 cancer-associated genes. Validation was done by qPCR-based approaches. A focus was on investigating marker performance in cfDNA from 88 patients (44 CRC, 44 controls). Finally, the workflow was scaled-up to perform 180plex analysis on 110 cfDNA samples, to identify a DNA methylation signature for advanced colonic adenomas (AA). A DNA methylation signature (n = 44) was deduced from microarray experiments and confirmed by quantitative methylation-specific PCR (qMSP) and by MSRE-qPCR, providing for six genes’ single areas under the curve (AUC) values of >0.85 (WT1, PENK, SPARC, GDNF, TMEFF2, DCC). A subset of the signatures can be used for patient stratification and therapy monitoring for progressed CRC with liver metastasis using cfDNA. Furthermore, we identified a 35-plex classifier for the identification of AAs with an AUC of 0.80.

Hypermethylation of the p15/INK4B Gene in Fanconi Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4296-4296
Author(s):  
Satoshi Hamanoue ◽  
Miharu Yabe ◽  
Hiromasa Yabe ◽  
Takayuki Yamashita
Keyword(s):  
Bone Marrow ◽  
Fanconi Anemia ◽  
Restriction Analysis ◽  
Bone Marrow Failure ◽  
Methylation Status ◽  
Age At Onset ◽  
Refractory Anemia ◽  
Molecular Abnormalities ◽  
Methylation Specific Pcr ◽  
Specific Pcr

Abstract Fanconi anemia (FA) is an inherited bone marrow failure syndrome with multiple complementation groups, characterized by genomic instability and predisposition to MDS and AML. Recent evidence indicates that multiple FA proteins are involved in DNA repair. Thus, increased genetic damage and secondary dysregulation of cell proliferation, differentiation and apoptosis are thought to play important roles in the development of bone marrow failure and subsequent progression to MDS/AML. However, little is known about molecular abnormalities responsible for these hematological disorders. Numerous studies indicated that epigenetic silencing of p15/INK4B, an inhibitor of cyclin-dependent kinases, plays an important role in the pathogenesis of MDS and AML. In the present study, we examined methylation status of 5′ CpG islands of the p15 gene in bone marrow mononuclear cells of FA patients, using methylation-specific PCR (MSP) and combined bisulfite restriction analysis (COBRA). Bone marrow samples were analyzed in 10 patients and serially studied in 4 of them. Hypermethylation of the p15 promoter region was detected in 5 patients (50%). This group included 3 patients with MDS: FA28-1 with refractory anemia (RA), FA87 with RAEB (RA with excess of blasts), and FA88 with later development of RA and progression to RAEB; whereas myelodysplasia was not observed in 2 patients (FA89, FA90). In two cases (FA88, FA90), p15 hypermethylation became negative during their courses, perhaps because of decreased myeloid cells. On the other hand, none of 5 patients without p15 hypermethylation had MDS. These results suggest that p15 hypermethylation is associated with development of MDS and occurs in the early phase of clonal evolution in the disease. Methylation status of p15 may be a useful prognostic factor of FA. Patient Age at onset (year old) Time from onset (month) Cytopenia MDS Cytogenetic abnormalities p15 methylation MSP b p15 methylation COBRA c a siblings, b MSP: methylation specific PCR, c COBRA: combined bisulfite restriction analysis, d ND: not determined FA28-1a 5 128 severe RA − − + 133 severe RA − + ++ FA87 8 252 severe RAEB + + +++ FA88 5 31 moderate − − + +++ 45 severe RA + − − 58 severe RAEB + + + FA89 5 49 mild − − + + 56 severe − − + + FA90 2 2 mild − − + ++ 31 severe − − − − FA28-2a 5 51 mild − − − NDd FA28-3a 3 12 mild − − − NDd FA47 3 15 mild − − − NDd FA68 5 46 moderate − − − NDd FA91 5 129 mild − − − NDd

Comparison of DNA Methylation and Expression Status Prior Azacytidine Treatment and their Relationship to Overall Survival and Clinical Response of MDS Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3777-3777
Author(s):  
Monika Belickova ◽  
Anna T Jonasova ◽  
Jitka Vesela ◽  
Eliska Stara ◽  
Andrea Hrustincova ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Clinical Response ◽  
Partial Remission ◽  
Methylation Status ◽  
Prognostic Impact ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Expression Status

Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis. High-risk MDS patients are treated by hypomethylating agents, of which they benefit significantly. However, only half of the patients respond positively to the treatment. Aberrant DNA methylation and mRNA expression in MDS were documented in several studies, but their prognostic impact in response to hypomethylating therapy is still unclear. The aim of the project was to find a relationship between methylation and expression status prior to azacytidine (AZA) treatment and the overall survival and clinical response of MDS patients. Methods We performed methylation and expression profiling in CD34+ cells from 30 samples from MDS patients before AZA treatment and after 4-8 treatment cycles. HumanMethylation27 BeadChips and HumanHT-12 v4 Expression BeadChips (Illumina) were used to generate profiles. DNA and RNA were isolated from same CD34+ cells separated from bone marrow by magnetic beads. The β-values represent quantitative measurements of DNA methylation levels of specific CpGs, and range from 0 for completely unmethylated to 1 for completely methylated DNA. The nonparametric Mann-Whitney test was used for comparison of β-values and expression levels between responders and nonresponders. Results To determine whether DNA methylation and expression might predict a response to AZA treatment, we compared methylation and expression status at baseline with clinical responses in 30 MDS patients. Twelve patients of 30 (40%) achieved complete remission or partial remission, 10 had stable disease (33.3%), and 8 showed progression (26.7%). Median survival after initiation of AZA treatment in progression patient group was 8.7 months, stable group 21.2 months, and group with complete or partial remission 24.5 months. We found significant differences in methylation status in 20 genes (p<0.05) between groups of responders and nonresponders and the largest methylation differences showed CALCA (0.61 vs. 0.16, p<0.05), MAGEE2 (0.71 vs. 0.30, p<0.05), HMP19 (0.62 vs. 0.23, p<0.05), MEOX1 (0.36 vs. 0.84, p<0.05), and KCNQ1DN genes (0.33 vs. 0.84, p<0.05). The aberrant expression status did not correlate with the response to AZA. We also measured methylation changes caused by AZA treatment. In the group of patients with progression, we did not find any change in the methylation profile after treatment. On the contrary, we found significant methylation changes after AZA treatment in the group of patients responding to treatment (e.g. AMT, NOTCH, and WT1genes). Conclusions Our finding of different DNA methylation levels at baseline between groups of responders and nonresponders as well as detection of decreased methylation after AZA treatment in the group of patients with clinical response may represent useful prediction markers of treatment success. However, the data require detailed examination along with confirmative cohort of patients. Supported by grant (NT/13899, NT/14377, NT/14539, NT/13847) and the project for conceptual development of research organization (00023736) from the Ministry of Health of the Czech Republic. Disclosures: No relevant conflicts of interest to declare.

Predictive significance of VEGF and HIF-1α expression in metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14672-e14672
Author(s):  
Veli Berk ◽  
Kemal Deniz ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Oktay Bozkurt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Benefit ◽  
Hypoxia Inducible Factor ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Vegf Expression ◽  
Primary Tumors ◽  
Colorectal Cancer Patients ◽  
Low Expression

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.

Intragenic hypomethylation of DNMT3A in patients with myelodysplastic syndrome

2018 ◽  
Vol 56 (3) ◽  
pp. 485-491 ◽  
Author(s):  
Ying-Ying Zhang ◽  
Jing-Dong Zhou ◽  
Dong-Qin Yang ◽  
Pin-Fang He ◽  
Dong-Ming Yao ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Methylation Status ◽  
World Health ◽  
Differentially Methylated Region ◽  
International Prognostic Scoring System ◽  
Aberrant Expression ◽  
Specific Pcr ◽  
Cell Counts

AbstractBackground:DNMT3Ais a DNA methyltransferase that acts inde novomethylation. Aberrant expression ofDNMT3Ahas been reported in several human diseases, including myelodysplastic syndrome (MDS). However, the pattern ofDNMT3Amethylation remains unknown in MDS.Methods:The present study was aimed to investigate the methylation status ofDNMT3Aintragenic differentially methylated region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze its clinical significance in MDS.Results:Aberrant hypomethylation ofDNMT3Awas found in 57% (51/90) MDS cases. There were no significant differences in age, sex, white blood cell counts, platelet counts, hemoglobin counts and World Health Organization, International Prognostic Scoring System and karyotype classifications betweenDNMT3Ahypomethylated andDNMT3Ahypermethylated groups. However, the patients withDNMT3Ahypomethylation had shorter overall survival time than those withoutDNMT3Ahypomethylation (11 months vs. 36 months, p=0.033). Multivariate analysis confirmed the independent adverse impact ofDNMT3Ahypomethylation in MDS.Conclusions:Our data suggest thatDNMT3ADMR2 hypomethylation may be a negative prognostic hallmark in MDS.

scholarly journals Local treatment combined with chemotherapy improves survival of patients with pulmonary metastases of colorectal cancer—a real-world retrospective study

2020 ◽  
Author(s):  
Zikai Cai ◽  
Qingbing Wang ◽  
Xiaofeng Yang ◽  
Xiaolong Ye ◽  
Jiafeng Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Free Survival

Abstract Background The effect of local treatments for pulmonary metastases from colorectal cancer (CRC-PM) remains controversial. This study aims to figure out whether local treatments combined with chemotherapy could improve patients’ survival by comparing the outcomes of CRC-PM patients who submitted to local interventions combined with chemotherapy or just chemotherapy.Patients and Methods From January 2009 to July 2019, a total of 119 patients with CRC-PM from two surgical centers were reviewed. Patients were divided into two groups according to treatments for the lung metastases: Local intervention combined with chemotherapy (Group-LI) and Chemotherapy alone (Group-Chem). Overall survival (OS) and progression-free survival (PFS) were assessed with the Kaplan-Meier method. Clinical characteristics associated with prognosis were analyzed by using a Cox proportional hazards regression model. Propensity score matching analyses were used to overcome the possible biases in some baseline characteristics.Result Multivariable analysis revealed that the level of carcinoembryonic antigen (CEA) and treatment for CRC-PM are independent predictors of both OS and PFS. The median OS in Group-LI (n = 39) and Group-Chem (n = 80) were 34.5 months and 13.8 months, respectively(P < 0.001). The 3-year progression-free survival rate in Group-LI and Group-Chem were 75.2% and 45.1% (P < 0.001). After propensity score matching, patients in Group-LI had better OS (HR = 3.304, P = 0.022) and PFS (HR = 4.029, P < 0.001) than Group-Chem.Conclusion. CRC-PM patients with lower lever of CEA or local treatment of lung metastases are more likely to be those with favorable prognosis. Selected CRC-PM patients could benefit from local treatment of pulmonary metastases.

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