scholarly journals Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 939
Author(s):  
Young Ju Jeong ◽  
Hoon Kyu Oh ◽  
Hye Ryeon Choi ◽  
Sung Hwan Park

Cluster of differentiation (CD) 73, which is encoded by the NT5E gene, regulates production of immunosuppressive adenosine and is an emerging checkpoint in cancer immunotherapy. Despite the significance of CD73 in immuno-oncology, the roles of the NT5E gene methylation in breast cancer have not been well-defined yet. Therefore, we aimed to investigate the prognostic significance of the NT5E gene methylation in breast cancer. The DNA methylation status of the NT5E gene was analyzed using pyrosequencing in breast cancer tissues. In addition, the levels of inflammatory markers and lymphocyte infiltration were evaluated. The mean methylation level of the NT5E gene was significantly higher in breast cancer than in normal breast tissues. In the analysis of relevance with clinicopathologic characteristics, the mean methylation levels of the NT5E gene were significantly higher in patients with large tumor size, high histologic grade, negative estrogen receptor expression, negative Bcl-2 expression, and premenopausal women. There was no difference in disease-free survival according to the methylation status of the NT5E gene. We found that the NT5E gene methylation was related to breast cancer development and associated with poor prognostic factors in breast cancer. Our results suggest that the NT5E gene methylation has potential as an epigenetic biomarker in breast cancer.

2001 ◽  
Vol 19 (7) ◽  
pp. 2033-2040 ◽  
Author(s):  
C.S. Chim ◽  
R. Liang ◽  
C.Y.Y. Tam ◽  
Y.L. Kwong

PURPOSE: To investigate the frequency of p15 and p16 gene promoter methylation in acute promyelocytic leukemia (APL), and to define its value in the detection of minimal residual disease (MRD) and treatment prognostication. PATIENTS AND METHODS: Bone marrow DNA obtained from 26 patients with APL at diagnosis and during follow-up was studied with the methylation-specific polymerase chain reaction (MS-PCR). Serial marrow DNA was studied by MS-PCR for MRD, and disease-free and overall survival were correlated with p15 methylation status at diagnosis. RESULTS: MS-PCR for p16 and p15 gene methylation has a maximum sensitivity of 10-4 and 10-5. At diagnosis, 19 patients (73.1%) exhibited p15 methylation, whereas only three patients (11.5%) exhibited p16 methylation, all of whom had concomitant p15 methylation. During follow-up, p16 methylation was acquired in two patients, one during the third hematologic relapse, and the other during transformation into therapy-related myelodysplastic syndrome. Six patients were evaluated serially with MS-PCR for p15 methylation at diagnosis and at follow-up examinations. Persistent p15 methylation preceded subsequent hematologic relapses in two patients, and conversion to negative MS-PCR for p15 methylation correlated with prolonged survival in another four patients. The 5-year disease-free survival of patients with p15 methylation was significantly inferior to that of patients without p15 methylation (15% v 62.5%; P = .02), and this remained significant in multivariate analysis. CONCLUSION: In APL, p15 but not p16 gene methylation is frequent. It is possible that p16 methylation is acquired during clonal evolution. p15 methylation is a potential marker of MRD and might be of prognostic significance.


Author(s):  
Fatma Özkan ◽  
Ilkay Tugba Unek ◽  
Olçun Ümit Ünal ◽  
Mustafa Emiroğlu ◽  
Asım Leblebici ◽  
...  

Objective: The overexpression of human epidermal growht factor-2 (HER-2) receptor is detected in 20% of patients with breast cancer. The prognosis is poor in patients with HER-2(+) breast cancer not receiving systemic therapy. Modified lymph node ratio (mLNR) and log odds of positive lymph nodes (LODDS) are the novel ratio-based classifications of lymph nodes in breast cancer. In literatüre, the data about the prognostic significance of mLNR ve LODDS is limited in patients with HER-2(+) breast cancer. The objective of the study was to evaluate the prognostic significance of mLNR and LODDS in patients with HER-2(+) breast cancer. Method: This study included 75 patients who were treated with adjuvant chemotherapy and trastuzumab for the diagnosis of HER-2(+) breast cancer between 2008-2013. The patients who received neoadjuvant chemotherapy or patients without axillary dissection were excluded from the study. Results: The mean disease-free survival and overall survival were 126.36±4.38 months (range: 117.78-134.95) and 128.87±3.32 months (range: 122.37-135.38), respectively. The mean disease-free survival was 127.30 months in patients with mLNR≤ 0.5 and 118.08 months in patients with mLNR> 0.5 (p=0.690). When the patients were classified into three groups according to LODDS values as LODDS1 (LODDS≤ -1.0), LODDS2 (-1.0<LODDS≤0) and LODDS3 (LODDS>0), the mean disease-free survival were 128.65 months, 114.07 months and 111.78 months, respectively (p=0.641). Conclusion: In this study, patients with HER-2(+) breast cancer were divided into risk groups according to mLNR and LODDS values, and a survival difference that could be clinically meaningful was observed between the groups, but was not statistically significant. There is a need for studies involving more patients on this subject. Our study highlights the prognostic significance of mLNR and LODDS in HER-2(+) breast cancer. Dividing HER-2(+) breast cancer into risk groups through mLNR and LODDS will help clinicians to develop optimal treatment and follow-up strategies.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lianghe Jiao ◽  
Jing Wei ◽  
Jun Ye ◽  
Chuanmeng Zhang

Background and Aim. Peroxiredoxin-1 (PRDX1) has been reported to be abnormally expressed in various malignancies. However, the prognostic role of PRDX1 in human solid tumors remains controversial. We performed this meta-analysis to accurately assess the prognostic significance of PRDX1 protein in patients with solid tumors. Methods. We comprehensively searched electronic databases, namely, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to December 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association between PRDX1 protein expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between PRDX1 protein expression and clinicopathologic characteristics in the patients. Results. Seventeen cohort studies that involved 2,858 patients were included in this meta-analysis. The pooled results indicated that positive PRDX1 expression was related to poor overall survival ( HR = 1.68 , 95% CI: 1.24-2.27, P = 0.001 ) and disease-free survival ( HR = 1.88 , 95% CI: 1.31-2.70, P = 0.001 ). In addition, high PRDX1 expression was associated with large tumor size ( OR = 1.69 , 95% CI: 1.07-2.68, P = 0.025 ), advanced TNM stage ( OR = 2.26 , 95% CI: 1.24-4.13, P = 0.008 ), and poor tumor differentiation ( OR = 0.59 , 95% CI: 0.44-0.81, P = 0.001 ). Conclusions. PRDX1 overexpression is associated with poor outcomes of cancers and may serve as a prognostic biomarker for malignant patients. Hence, PRDX1 could be a new target for antitumor therapy.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1952
Author(s):  
Elżbieta Zarychta ◽  
Barbara Ruszkowska-Ciastek ◽  
Kornel Bielawski ◽  
Piotr Rhone

(1) Background: Tumour angiogenesis is critical for the progression of neoplasms. A prospective study was designed to examine the utility of stromal cell-derived factor 1α (SDF-1α) and selected vasculo-angiogenic parameters for estimating the probability of disease relapse in 84 primary, operable invasive breast cancer (IBrC) patients (40 (48%) with stage IA and 44 (52%) with stage IIA and IIB). (2) Methods: We explored the prognostic value of the plasma levels of SDF-1α, vascular endothelial growth factor A (VEGF-A), the soluble forms of VEGF receptors type 1 and 2, and the number of circulating endothelial progenitor cells (circulating EPCs) in breast cancer patients. The median follow-up duration was 58 months, with complete follow-up for the first event. (3) Results: According to ROC curve analysis, the optimal cut-off point for SDF-1α (for discriminating between patients at high and low risk of relapse) was 42 pg/mL, providing 57% sensitivity and 75% specificity. Kaplan–Meier curves for disease-free survival (DFS) showed that concentrations of SDF-1α lower than 42 pg/dL together with a VEGFR1 lower than 29.86 pg/mL were significantly associated with shorter DFS in IBrC patients (p = 0.0381). Patients with both SDF-1α lower than 42 pg/dL and a number of circulating EPCs lower than 9.68 cells/µL had significantly shorter DFS (p = 0.0138). (4) Conclusions: Our results imply the clinical usefulness of SDF-1α, sVEGFR1 and the number of circulating EPCs as prognostic markers for breast cancer in clinical settings.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serena Scomersi ◽  
Fabiola Giudici ◽  
Giuseppe Cacciatore ◽  
Pasquale Losurdo ◽  
Stefano Fracon ◽  
...  

AbstractMale breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p  = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.


2017 ◽  
Vol 27 (3) ◽  
pp. 199-205
Author(s):  
Maximiliano Cassilha Kneubil ◽  
◽  
Alessandra Eifler Guerra Godoy ◽  
Guilherme Portela Coelho ◽  
Rafael Grochot ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keunyoung Kim ◽  
In-Joo Kim ◽  
Kyoungjune Pak ◽  
Taewoo Kang ◽  
Young Mi Seol ◽  
...  

Abstract Background This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. Methods The medical records of 288 patients who had undergone surgical resection for stages I–III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. Results Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. Conclusions A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.


2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.


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