PurposeTo compile a list of genes that have been reported to be affected by external ionizing radiation (IR) and to assess their performance as candidate biomarkers for individual human radiation dosimetry.MethodsEligible studies were identified through extensive searches of the online databases from 1978 to 2017. Original English-language publications of microarray studies assessing radiation-induced changes in gene expression levels in human blood after external IR were included. Genes identified in at least half of the selected studies were retained for bio-statistical analysis in order to evaluate their diagnostic ability.Results24 studies met the criteria and were included in this study. Radiation-induced expression of 10,170 unique genes was identified and the 31 genes that have been identified in at least 50% of studies (12/24 studies) were selected for diagnostic power analysis. Twenty-seven genes showed a significant Spearman’s correlation with radiation dose. Individually, TNFSF4, FDXR, MYC, ZMAT3 and GADD45A provided the best discrimination of radiation dose < 2 Gy and dose ≥ 2 Gy according to according to their maximized Youden’s index (0.67, 0.55, 0.55, 0.55 and 0.53 respectively). Moreover, 12 combinations of three genes display an area under the Receiver Operating Curve (ROC) curve (AUC) = 1 reinforcing the concept of biomarker combinations instead of looking for an ideal and unique biomarker.ConclusionGene expression is a promising approach for radiation dosimetry assessment. A list of robust candidate biomarkers has been identified from analysis of the studies published to date, confirming for example the potential of well-known genes such as FDXR and TNFSF4 or highlighting other promising gene such as ZMAT3. However, heterogeneity in protocols and analysis methods will require additional studies to confirm these results.
Plant-based scaffolds present many advantages over a variety of biomaterials. Recent studies explored their potential to be repopulated with human cells and thus highlight a growing interest for their use in tissue engineering or for biomedical applications. However, it is still unclear if these in vitro plant-based scaffolds can modify cell phenotype or affect cellular response to external stimuli. Here, we report the characterization of the mechano-regulation of melanoma SK-MEL-28 and prostate PC3 cells seeded on decellularized spinach leaves scaffolds, compared to cells deposited on standard rigid cell culture substrate, as well as their response to drug and radiation treatment. The results showed that YAP/TAZ signaling was downregulated, cellular morphology altered and proliferation rate decreased when cells were cultured on leaf scaffold. Interestingly, cell culture on vegetal scaffold also affected cellular response to external stress. Thus, SK-MEL-28 cells phenotype is modified leading to a decrease in MITF activity and drug resistance, while PC3 cells showed altered gene expression and radiation response. These findings shed lights on the decellularization of vegetal materials to provide substrates that can be repopulated with human cells to better reproduce a soft tissue microenvironment. However, these complex scaffolds mediate changes in cell behavior and in order to exploit the capability of matching physical properties of the various plant scaffolds to diverse physiological functionalities of cells and human tissue constructs, additional studies are required to better characterize physical and biochemical cell-substrate interactions.
Evidence of circulating autoantibodies in cancer patient sera has created opportunities for exploiting them as biomarkers. We report the identification and the clinical validation of an autoantibody panel in newly diagnosed patients with early-stage breast cancer. Proteomic approach and serological screening of a discovery set of sera (n 5 80) were performed to identify tumor-associated antigens (TAAs). Autoantibody levels were then measured in an independent validation set (n 5 182) against a panel of five TAAs by enzyme-linked immunosorbent assay. Sixty-seven antigens that elicited a specific humoral response in breast cancer were identified and five antigens (GAL3, PAK2, PHB2, RACK1 and RUVBL1) were selected for validation. GAL3 and RACK1 showed significantly increased reactivity in early-stage breast cancer. When combined, the five markers significantly discriminated early-stage cancer from healthy individuals ( Breast cancer is the most common malignant disease in women in western countries, comprising $35% of all cancers. 1 The incidence of breast cancer has increased over the past few decades, probably due to earlier diagnosis, and mortality has been gradually reducing. 2 Nonetheless, prevention and early detection of breast cancer are two major issues of consideration because appropriate treatment can greatly reduce breast cancer-related mortality if breast cancer is detected at an early stage. 3 There is evidence from several randomized controlled trials that the widespread use of mammography as a screening tool is associated with a decreased breast cancer mortality rate. 4 However, not all breast cancers can be detected by mammography. These false-negative mammograms can be attributed to technical or interpretive reasons including the absence of calcifications and, more importantly, the high breast density. 5,6 The actual percentage of patients presenting mammographically occult primary tumors at diagnosis has been stated to be as high as 35% in younger women 7 but generally is quoted to be in the range of 9-22%. 8 Therefore, considerable efforts have been undertaken to produce an effective screening method for earlystage breast cancer. Both full-field digital mammography and computer-aided detection programs have been proposed, but results from these two methods remain controversial. 9 The ability of magnetic resonance imaging (MRI) to detect the presence and extent of small tumors seems to exceed that of mammography or ultrasound, with low specificity; however additional careful investigations are still required. 10 Finally, improving early-stage breast cancer screening is needed, particularly for women with high breast density.Serum biomarkers are noninvasive and reproducible screening tools that would enhance diagnostic capabilities to complement the currently available diagnostic tests. Over the past few years, evidence of circulating autoantibodies in the sera of cancer patients has created opportunities for exploiting the immune system as a source of cancer biomarkers. The immune response is tri...
The widespread use of screening mammography has resulted in increased detection of early-stage breast disease, particularly for in situ carcinoma and early-stage breast cancer. However, the majority of women with abnormalities noted on screening mammograms are not diagnosed with cancer because of several factors, including radiologist assessment, patient age, breast density, malpractice concerns, and quality control procedures. Although magnetic resonance imaging is a highly sensitive detection tool that has become standard for women at very high risk of developing breast cancer, it lacks sufficient specificity and costeffectiveness for use as a general screening tool. Therefore, there is an important need to improve screening and diagnosis of early-invasive and noninvasive tumors, that is, in situ carcinoma. The great potential for molecular tools to improve breast cancer outcomes based on early diagnosis has driven the search for diagnostic biomarkers. Identification of tumor-specific markers capable of eliciting an immune response in the early stages of tumor development seems to provide an effective approach for early diagnosis. The aim of this review is to describe several autoantibodies identified during breast cancer diagnosis. We will focus on these molecules highlighted in the past two years and discuss the potential future use of autoantibodies as biomarkers of early-stage breast cancer.
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