A panel of circulating non-coding RNAs in the diagnosis and monitoring of therapy in Egyptian patients with breast cancer

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC

Factors associated with late-stage diagnosis of breast cancer among Egyptian women

Background: Detecting Breast Cancer (BC) at earlier stages comes with a better prognosis, while diagnosis at late stages has poor outcomes and escalating mortality rates from the disease. The study aims to understand the factors associated with the latestage diagnosis of BC in Egypt. Design and Methods: A sample of 400 women with a pathologically confirmed BC were enrolled from one of the main tertiary cancer hospitals in Egypt. A cross-sectional study design was conducted. The collected data included: clinical characteristics of the tumor, socio-demographic characteristics of the studied women, reproductive and medical history, screening practices, and the time from symptom onset to definite diagnosis as suspected predictors to the stage of BC at diagnosis. Data was analyzed by crude odds ratios (95% confidence interval) and multivariate logistic regression analysis. Results: The study revealed that 47.5% were diagnosed at late stages (40% at stage III/ 7.5% at stage IV), while (52.5%) were diagnosed at early stages (6.5% at stage I/46% at stage II). A binary logistic regression model showed that unmarried females (p=0.012), had non-luminal molecular subtype of BC including HER2 enriched and triple-negative tumors (p<0.001), presentation with breast changes and a non-palpable lump (p=0.024) or nonbreast symptoms (P=0.002), a delay longer than 3 months to the first presentation by patients (p<0.001), and a delay to definite diagnosis longer than 1 month by providers (p<0.001) were significant risk factors of late-stage diagnosis of BC. Conclusions: Late-stage diagnosis of BC in Egypt is associated with the aggressiveness of some molecular subtypes and other important modifiable factors that should be addressed

A Panel of Circulating Non-Coding RNAs in the Diagnosis and Monitoring of Therapy in Egyptian Patients with Breast Cancer

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC

A low serum microRNA-497-5p expression level is associated with primary breast cancer among Egyptian female patients

Background/aim Circulating forms of micro(mi)RNAs are nowadays increasingly recognized as noninvasive promising biomarkers for early diagnosis and management of breast cancer (BC). Among the numerous miRNAs studied in BC, tissue expressed miR-497-5p and miR-182-5p proved to serve as promising diagnostic, prognostic, and therapeutic target tools in BC; yet little is known about their circulating forms in the peripheral blood of such patients. The study aimed to evaluate serum expression levels of miR-497-5p and miR-182-5p in Egyptian female patients with newly diagnosed BC and their possible association with different clinicopathological features. Patients and methods The study was conducted on 50 primary BC patients at the Medical Research Institute, Alexandria, Egypt, in addition to 50 healthy female volunteers as a control group. Preoperative serum samples were taken from all patients and from healthy volunteers. Relative quantifications of serum miR-182-5p and miR-497-5p expression levels were done using a reverse transcription-quantitative real time PCR. Results The study showed that the median value for fold change in serum miR-497-5p expression was significantly down regulated in BC patients group compared to the healthy control group. A receiver operating characteristics curve generated a cutoff value of 0.54. In serum miR-497-5p expression level was used to discriminate BC patients from controls with a diagnostic specificity of 88%, a sensitivity of 56%, and an overall test accuracy of 68.8%. However, no statistically significant difference was noted in serum miR-182-5p expression level between BC patients and control group. Nevertheless, its serum expression level was significantly higher in BC patients with lymph node involvement compared with BC patients without nodal involvement. Conclusion The downregulated serum miR-497-5p expression in BC patients compared with the healthy control group points to loss of its protective role in such BC patients. Further studies of this miRNA on a larger sample of patients with different molecular subtypes are recommended

Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study

PURPOSEEarly-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients.MATERIALS AND METHODSThis was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years).RESULTSThe study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported.CONCLUSIONA comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC

Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

BACKGROUND: Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available. Identifying which patients are unlikely to respond to adjuvant chemotherapy from among those who are eligible for such treatment would be a major step towards treatment personalization. It would spare such patients from unnecessary toxicities and would improve the allocation of societal healthcare resources. METHODS/DESIGN: PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer. The study’s primary objective is to examine the ability of PET/CT-assessed tumor FDG uptake after one course of preoperative chemotherapy to predict the outcome of adjuvant therapy, as measured by 3-year disease-free survival. Secondary objectives are to examine the predictive value of changes in PET/CT-assessed tumor FDG uptake on overall survival, to define the best cut-off value of FDG uptake for predicting treatment outcome, and to analyse the cost-effectiveness of such preoperative chemo-sensitivity testing. At study planning, exploratory translational research objectives were 1) to assess the predictive value of circulating tumor cells for disease-free survival, 2) to examine the predictive value of single nucleotide polymorphisms for disease-free survival with respect to genes related either to toxicity or to drug targets, 3) to assess genomic rearrangements associated with response or resistance to FOLFOX treatment, 4) to identify an immunologic signature associated with metabolic tumor response to FOLFOX therapy and, finally, 5) to create a bank of frozen tumor samples for future studies. DISCUSSION: PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer. EUDRACT NUMBER: 2009-011445-13 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT0099486

Erratum: Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

Erratum for Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study. [BMC Cancer. 2013

PFS* (A) and OS* (B) distribution according to the 4 classes of metabolic response.

<p>Class 1: no metabolic unresponsive lesion; Class 2: minority of unresponsive lesion among whole body target tumour load; Class 3: majority of whole body target tumour load does not respond; Class 4: all target lesions are non-responding, or, presence of progressive lesions [progression defined as >25% increase of FDG uptake on second PET, or appearance of a new lesion]. *from date of the second FDG PET-CT.</p

Consort Diagram.

<p>Consort Diagram.</p