A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.

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Non-Invasive Biomarkers for Early Detection of Breast Cancer

Cancers ◽

10.3390/cancers12102767 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2767

Author(s):

Jiawei Li ◽

Xin Guan ◽

Zhimin Fan ◽

Lai-Ming Ching ◽

Yan Li ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

False Negative ◽

Breast Cancer Diagnosis ◽

Diagnostic Biomarkers ◽

Circulating Micrornas ◽

Non Invasive ◽

Common Cancer ◽

Volatile Organic

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

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Proteomic Patterns of Nipple Aspirate Fluids Obtained by SELDI-TOF: Potential for New Biomarkers to Aid in the Diagnosis of Breast Cancer

Disease Markers ◽

10.1155/2001/674959 ◽

2001 ◽

Vol 17 (4) ◽

pp. 301-307 ◽

Cited By ~ 192

Author(s):

Cloud P. Paweletz ◽

Bruce Trock ◽

Marie Pennanen ◽

Theodore Tsangaris ◽

Collette Magnant ◽

...

Keyword(s):

Breast Cancer ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Ionization Time ◽

Non Invasive ◽

Abnormal Mammogram ◽

Surface Enhanced ◽

Invasive Method ◽

Nipple Aspirate Fluids ◽

New Biomarkers

Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.

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Fecal CEA Has an Advantage in the Diagnosis of Colorectal Cancer at Early Stage

Cancer Control ◽

10.1177/10732748211048292 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110482

Author(s):

Linfang Li ◽

Shan Xing ◽

Miantao Wu ◽

Yufeng Ao ◽

Xin Zheng ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Diagnosis ◽

Diagnostic Accuracy ◽

Early Stage ◽

Healthy Controls ◽

Diagnostic Biomarker ◽

Diagnostic Efficacy ◽

Non Invasive ◽

Serum Carcinoembryonic Antigen

Purpose Serum carcinoembryonic antigen (SCEA) level is often measured in patients with CRC but suffers from poor sensitivity and specificity as a diagnostic biomarker. CEA is more abundant in stool than in serum, but it has not been widely studied. This study aimed to elucidate the efficacy of fecal CEA (FCEA) as a potential non-invasive biomarker for early diagnosis of CRC. Materials and Methods We retrospectively analyzed the determination of FCEA and SCEA levels by electrochemiluminescence. We evaluated the diagnostic accuracy of FCEA and SCEA levels in early-stage CRC patients and healthy controls using ROC curve. Results A total of 298 people were included: 115 patients with CRC, 35 patients with adenomatous polyp (APC), 46 patients with non-gastrointestinal cancer (NGC), and 102 healthy controls (HC). The FCEA concentrations in CRC and APC patients were significantly higher than that of NGC and HC, and this is different from SCEA expression in APC and NGC. As a diagnostic biomarker of CRC, FCEA had significantly larger AUC compared with SCEA (.802 vs .735, P < .001). For identifying early-stage colorectal cancer, FCEA showed better diagnostic efficacy (AUC: .831) than SCEA (AUC: .750), and the combination of the 2 biomarkers was even higher (AUC: .896). The sensitivity of FCEA was higher than that of SCEA (78.7% vs 29.8%). When SCEA was negative, 80.3% of CRC and 54.6% of APC cases could be identified by FCEA. Conclusion Compared with SCEA, FCEA has more advantages in the diagnosis of the early stage of colorectal cancer and adenomatous polyps.

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Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

Experimental Biology and Medicine ◽

10.1177/1535370220945987 ◽

2020 ◽

Vol 245 (16) ◽

pp. 1428-1436

Author(s):

Zhi-Jun Zhang ◽

Xing-Guo Song ◽

Li Xie ◽

Kang-Yu Wang ◽

You-Yong Tang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Early Stage Nsclc ◽

Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

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Uncommon Breast Malignancies: Presentation Pattern, Prognostic Issue and Treatment Outcome in an Italian Single Institution Experience

Tumori Journal ◽

10.1177/030089161309900107 ◽

2013 ◽

Vol 99 (1) ◽

pp. 39-44

Author(s):

Claudia Maria Regina Bareggi ◽

Dario Consonni ◽

Barbara Galassi ◽

Donatella Gambini ◽

Elisa Locatelli ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Outcome ◽

Invasive Ductal Carcinoma ◽

Ductal Carcinoma ◽

Early Stage ◽

Medullary Carcinoma ◽

Mucinous Carcinoma ◽

Lymph Node Involvement ◽

Tubular Carcinoma ◽

Breast Malignancies

Aims and background Often neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series. Patients and methods Of 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome. Results Rare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12–0.62; P = 0.002). Conclusions According to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.

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Descriptive analysis of 192 cases of breast cancer occurring before age 40 in Yaounde, Cameroon

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20172898 ◽

2017 ◽

Vol 6 (7) ◽

pp. 2704 ◽

Cited By ~ 1

Author(s):

Félix Essiben ◽

Pascal Foumane ◽

Esther JNU Meka ◽

Michèle Tchakounté ◽

Julius Sama Dohbit ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma ◽

Early Stage ◽

Descriptive Analysis ◽

Survival Rates ◽

The United States ◽

Therapeutic Modalities ◽

History Of ◽

Case Files ◽

Common Histological Type

Background: Breast cancer is today a global health problem. With 1,671,149 new cases diagnosed in 2012, it is the most common female cancer in the world and accounts for 11.9% of all cancers and it affects more people than prostate cancer. In 2008, The United States statistics showed that, for all cancer that affect women before 40 years, more than 40% of them concerned the breast. The aim of this study was to describe the clinical, histopathological and therapeutic aspects of breast cancer in women under 40 years of age in Yaoundé.Methods: This was a retrospective study with data collected from 192 medical case files of women treated over a period of 12 years, from January 2004 to December 2015 at the Yaounde General Hospital and the Yaounde Gyneco-Obstetric and Pediatric Hospital. Microsoft Epi Info version 3.4.5 and SPSS version 20.0 softwares were used for data analysis.Results: From 2004 to 2015, 1489 cases of breast cancer were treated in both hospitals. Of these, 462 women were less than 40 years old, representing a proportion of 31.0%. The mean age at diagnosis was 33.5±5.0 years and 17.7% of women had a family history of breast cancer. The average time before an initial consultation was 6.7±6.6 months. Most cases were classified as T4 (46.1%). The most common histological type was ductal carcinoma (87.4%). Grades SBR II and SBR III were predominant (76.4%). Axillary dissection (64.4%) and neoadjuvant chemotherapy (43.9%) were the main therapeutic modalities. The overall survival rate at 5 years was 51.2%. Five-year survival rates with no local recurrence and no metastatic occurrence were 35.8% and 43.2% respectively.Conclusions: Breast cancer largely affects women under the age of 40 and is often discovered late, at an advanced stage. The prognosis appears poor. Only screening could facilitate diagnosis at an early stage of the disease for better outcomes.

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Diagnostic Accuracy of Axillary Ultrasound in Early–Stage Breast Cancer

Indian Journal of Surgery ◽

10.1007/s12262-018-1828-y ◽

2018 ◽

Vol 81 (5) ◽

pp. 421-425

Author(s):

Tugba Han Yilmaz ◽

Hasan Yerli ◽

Baha Arslan ◽

Varlık Erol ◽

Huseyin Gulay

Keyword(s):

Breast Cancer ◽

Diagnostic Accuracy ◽

Early Stage ◽

Early Stage Breast Cancer ◽

Axillary Ultrasound

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Intraoperative radiation therapy for early stage breast cancer: experiences from Iran

10.21203/rs.3.rs-57682/v1 ◽

2020 ◽

Author(s):

Vahid Zangouri ◽

Hamid Nasrollahi ◽

Ali Taheri ◽

Majid Akrami ◽

Peyman Arasteh ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Patient Selection ◽

Tumor Size ◽

Ductal Carcinoma ◽

Early Stage ◽

Intraoperative Radiation Therapy ◽

Study Patient ◽

Intraoperative Radiation

Abstract Background and objective Currently no definite guideline exists on the use of intraoperative radiation therapy (IORT) among patients with early stage BC. We report our experiences with IORT among breast cancer (BC) patients in our region.Methods All patient who received radical IORT from April 2014 on to March 2020 were included in the study. Patient selection criteria were as followed: age equal or older than 45 years old; all cases of invasive carcinomas, moreover in lobular carcinomas only after MRI and confirmation, and in cases with ductal carcinoma in-situ (DCIS) only those with low, intermediate grade, tumor size of equal or less than 2.5cm and a margin of 2-3mm; those between 45 and 50 years old with a tumor size of 0-2cm, those between 50 and 55 years old with a tumor size of 2-2.5cm, and those ≥55 years old with a tumor size of 2.5-3cm; those with invasive tumors a negative margin and in cases of DCIS a margin of 3mm; a negative nodal status (exception in patients with micrometastasis); and a positive estrogen receptor status. Results Overall, 252 patients entered the study. Mean (SD) age of patients was 56.43±7.79 years. In total, 32.9% of patients had a family history of BC. Mean tumor size was 1.56±0.55 cm. Median (IQR) follow-up of patients was 24 (13, 36) months. Overall, 6 patients (2.4%) experienced recurrence in follow-up visits, among which three (1.2%) were local recurrence, two (0.8%) were regional recurrence and one patients (0.4%) had metastasis.Median (IQR) time to recurrence was 23 (13, 36) among the six patient who had recurrence. Overall, 11 patients (4.3%) with DCIS in our study received IORT. All these patients had free margins in histopathology examination. None of these patients experience recurrence.Conclusion For the first time, we categorized patients according to age and tumor size and older patients with larger tumor sizes were considered appropriate candidates for IORT. Our series showed a successful experience with the use of IORT in a region where facilities for IORT are limited using our modified criteria for patient selection.

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Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.667212 ◽

2021 ◽

Vol 11 ◽

Author(s):

Haiming Huang ◽

Jialin Du ◽

Bo Jin ◽

Lu Pang ◽

Nan Duan ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Progression ◽

Rna Sequencing ◽

Molecular Mechanisms ◽

Early Stage ◽

Healthy Controls ◽

Direct Products ◽

Diagnostic Biomarkers ◽

Diagnostic Potential ◽

Urine Exosomes

BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.

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Probing of breast cancer using a combination of plasma and urinary circulating cell-free DNA

Bioscience Reports ◽

10.1042/bsr20194306 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Zhigang Zuo ◽

Jiying Tang ◽

Xiaojun Cai ◽

Feng Ke ◽

Zhenzong Shi

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Pik3ca Mutation ◽

Early Stage Breast Cancer ◽

Healthy Controls ◽

Cell Free Dna ◽

Clinical Sensitivity ◽

Free Dna ◽

Urine Specimens ◽

Circulating Cell Free Dna

Abstract Monitoring of early-stage breast cancer is critical in promptly addressing disease relapse. Circulating cell-free DNA provides a minimally invasive and sensitive means to probing the disease. In a longitudinal analysis of 250 patients with early breast cancer, we compared the circulating cell-free DNA recovered from both plasma and urine specimens. For comparison, 50 healthy controls were also recruited. Specific mutations associated with the disease were profiled to determine the clinical sensitivity and specificity. Correlations of recovered concentrations of cell-free DNA with outcomes were examined to address early prognostication. PIK3CA mutation profiling in both plasma and urinary cell-free DNA showed an agreement of 97.2% compared with the results obtained for tumor tissues. The analysis of healthy controls revealed that cell-free DNA measurements were stable and consistent over time. Over the short 6-month period of monitoring, our analyses showed declines in recovered cell-free DNA; these findings may aid physicians in stratifying patients at higher risk for relapse. Similar results were observed in both plasma and urine specimens (hazard ratios: 2.16 and 2.48, respectively). Cell-free DNA presents a novel and sensitive method for the monitoring of early-stage breast cancer. In the present study, serial measurements of both plasma and urine specimens were useful in probing the disease.

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