Serum Tumor Markers for Detection of Bone Metastasis in Breast Cancer Patients

Abstract Background Aberrant DNA methylation of phosphatase and tensin homolog (PTEN) gene has been found in many cancers. The object of this study was to evaluate the clinical impact of PTEN methylation as a prognostic marker in breast cancer. The study includes 153 newly diagnosed females, and they were divided according to their clinical diagnosis into breast cancer patients (n = 112) and females with benign breast lesion (n = 41). A group of healthy individuals (n = 25) were recruited as control individuals. Breast cancer patients were categorized into early stage (0–I, n = 48) and late stage (II–III, n = 64), and graded into low grade (I–II, n = 42) and high grade (III, n = 70). Their pathological types were invasive duct carcinoma (IDC) (n = 66) and duct carcinoma in situ (DCI) (n = 46). Tumor markers (CEA and CA15.3) were detected using ELISA. DNA was taken away from the blood, and the PTEN promoter methylation level was evaluated using the EpiTect Methyl II PCR method. Results The findings revealed the superiority of PTEN methylation status as a good discriminator of the cancer group from the other two groups (benign and control) with its highest AUC and increased sensitivity (96.4%) and specificity (100%) over tumor markers (50% and 84% for CEA and 49.1% and 86.4% for CA15.3), respectively. The frequency of PTEN methylation was 96.4% of breast cancer patients and none of the benign and controls showed PTEN methylation and the means of PTEN methylation (87 ± 0.6) were significantly increased in blood samples of breast cancer group as compared to both benign and control groups (25 ± 0.7 and 12.6 ± 0.3), respectively. Methylation levels of PTEN were higher in the blood of patients with ER-positive than in patients with ER-negative cancers (P = 0.007) and in HER2 positive vs. HER2 negative tumors (P = 0.001). The Kaplan-Meier analysis recognizes PTEN methylation status as a significant forecaster of bad progression-free survival (PFS) and overall survival (OS), after 40 months follow-up. Conclusions PETN methylation could be supposed as one of the epigenetic aspects influencing the breast cancer prognosis that might foretell more aggressive actions and worse results in breast cancer patients.

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Lesion-Based Bone Metastasis Detection in Chest Bone Scintigraphy Images of Prostate Cancer Patients Using Pre-Train, Negative Mining, and Deep Learning

Diagnostics ◽

10.3390/diagnostics11030518 ◽

2021 ◽

Vol 11 (3) ◽

pp. 518

Author(s):

Da-Chuan Cheng ◽

Te-Chun Hsieh ◽

Kuo-Yang Yen ◽

Chia-Hung Kao

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Deep Learning ◽

Bone Metastasis ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Breast Cancer Patients ◽

Location Detection ◽

The Mean ◽

Mean Sensitivity

This study aimed to explore efficient ways to diagnose bone metastasis early using bone scintigraphy images through negative mining, pre-training, the convolutional neural network, and deep learning. We studied 205 prostate cancer patients and 371 breast cancer patients and used bone scintigraphy data from breast cancer patients to pre-train a YOLO v4 with a false-positive reduction strategy. With the pre-trained model, transferred learning was applied to prostate cancer patients to build a model to detect and identify metastasis locations using bone scintigraphy. Ten-fold cross validation was conducted. The mean sensitivity and precision rates for bone metastasis location detection and classification (lesion-based) in the chests of prostate patients were 0.72 ± 0.04 and 0.90 ± 0.04, respectively. The mean sensitivity and specificity rates for bone metastasis classification (patient-based) in the chests of prostate patients were 0.94 ± 0.09 and 0.92 ± 0.09, respectively. The developed system has the potential to provide pre-diagnostic reports to aid in physicians’ final decisions.

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Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions

Oncogene ◽

10.1038/s41388-020-01603-6 ◽

2021 ◽

Author(s):

Francesco Pantano ◽

Martine Croset ◽

Keltouma Driouch ◽

Natalia Bednarz-Knoll ◽

Michele Iuliani ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Bone Metastasis ◽

Tumor Cell ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Osteolytic Lesions ◽

Cell Colonization

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

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