Molecular Biomarkers For Early Detection Research Articles

Epigenomic biomarkers of cardiometabolic disease: How far are we from daily practice?

Determining whether someone has cardiometabolic disease (CMD), especially in the early stages, can be complicated. Risk stratification ordinarily depends on an extended process relying on medical history that typically considers blood pressure, cholesterol, smoking and diabetes status. Physicians have long relied on these key patient characteristics to assess CMD risk. However, these widely used clinical assessments are often identified later in life and by definition, in those individuals with progressed disease. This is partly because the onset of CMD naturally occurs in adulthood, however, the underlying processes can occur much earlier in life, even in the absence of obvious symptoms. For one thing, the pathways towards pathology may exist for years before symptom onset. Thus, among other things, there are opportunities to provide doctors with better insights into future disease prediction especially in younger adults with diabetes. The rapid rise in CMD together with the increased rates of obesity and diabetes in this population only emphasises the importance of predictive molecular biomarkers. One notable aspect is that traditional risk scores, such as those based on cholesterol measurements, are frequently found to be within normal ranges in younger populations. At the same time, given the significant overlap in risk factors for cardiovascular disease (CVD) and diabetes, the unmet clinical need is for early biomarkers of CMD that may help improve risk assessment in younger adults. This editorial highlights advances in the use of polygenic risk scores and emerging utility of genetic biomarkers to define intermediate CMD phenotypes discussing new classification criteria involving DNA methylation of genes to improve risk assessment. CMD is the number one cause of mortality and accounts for 31% of all global deaths. CMD is also multifactorial, comprising cardiovascular disease (CVD) and diabetes that have significant overlap in risk factors and disease biology. Diabetes is arguably the strongest risk factor for CVD development. Accounting for almost 90% of diabetes cases worldwide, type 2 diabetes (T2D) affects about 527 million people. The global economic burden is estimated at 1.3 trillion USD annually and is close to 1.8% of global GDP [1]. Despite the progress in preventive and therapeutic measures of CVD, the increasing CMD rates only underscore the important need of molecular biomarkers for early detection [2]. Determining whether someone has CMD usually involves an extended diagnostic process that has become essential for risk stratification and disease prevention [3]. While the onset of CMD typically occurs in adulthood, disease development commences much earlier, and this has scientists questioning whether molecular biomarkers could improve current prognostic risk scores. Predicting which people with T2D are most likely to develop CVD remains a significant challenge despite the recent advances in genetic mapping.Graphical abstract

Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma.

High prevalence of CD44 and its ligand low molecular weight hyaluronan in plasma of HNSCC patients: clinical significance.

This study aims to evaluate the role of cancer stem cell marker, CD44, and its ligand HA as potential molecular biomarker for early detection of HNSCC. The expression profile (mRNA/Protein) of CD44 variants were analysed in primary HNSCC lesions and plasma of the patients. Then, prevalence of HA variants was analysed in plasma of the patients. The mRNA expression of CD44 variants, CD44S and CD44v3, were significantly high in both early (stage I/II) and late (stage III/IV) invasive lesions, with predominant expression of CD44v3 in the late-stage lesions. In plasma of HNSCC patients, increased levels of SolCD44, CD44-ICD and unique 62 KD CD44 variants with respect to standard CD44S were seen, in comparison to their prevalence in plasma of normal individuals. The abundance of CD44-ICD and 62 KD variants were significantly high in plasma of late stage HNSCC patients. Interestingly, significantly high level of low molecular weight HA(LMW HA) with respect to high molecular weight HA(HMW HA) was seen in plasma of HNSCC patients irrespective of clinical stages. On the contrary, high HMW HA level in plasma of normal individuals was seen. The high level of LMW HA in plasma of HNSCC patients might be due to combinatorial effect of increased mRNA expression of HA synthesizing enzyme HAS1/2/3 and HA degrading enzyme HYAL1/2, as seen in the primary HNSCC samples. Thus, our data revealed the importance of specific CD44 and HA variants in plasma of HNSCC patients during its development as potential non-invasive molecular biomarker of the disease.

Omics sciences and precision medicine in sarcoma.

Sarcomas are a relatively rare but diverse group of cancers that typically develop in the mesenchymal cells of bones and soft tissues. Occurring in more than 70 subtypes, sarcomas have broad histological presentations, posing significant challenges of prognosis and treatment. Modern multi-omics studies, which include genomics, proteomics, metabolomics, and micro-biomics, are vital to understand the underlying mechanisms of sarcoma development and progression, identify molecular biomarkers for early detection, develop personalized treatment plans, and discover drug resistance mechanisms in sarcomas to upsurge the survival rate. This study aims to highlight the genetic risk factors responsible for sarcoma-genesis, and to present a comprehensive review of multi-omics studies about sarcoma. Extensive literature research was undertaken using reliable and authentic medical journals, e-books, and online cancer research databases. Mendelian inheritance in man database (OMIM) was explored to study particular genes and their loci that are responsible to cause various sarcomas. This in-depth research led to the finding out that omics studies provide a more comprehensive understanding of underlying molecular mechanisms of sarcomas. Through genomics, we can reveal genetic alterations that predispose to sarcoma, like mutation in TP53, NF1, and so on. Pharmacogenomics enable us to find molecular targets for specific drugs. Whereas, proteomic and metabolomic studies provide insights into the biological pathways involved in sarcoma development and progression. Future advancements in omics sciences for sarcoma are on the cutting-edge of defining precision treatment plans and improved resilience of sarcoma patients.

Tears as a Source of Biomarkers in the Diagnosis of Graves’ Orbitopathy

Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves' disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves' orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, there is great interest in searching for precise molecular biomarkers for early detection, disease monitoring, and clinical management. Researchers are keen to identify novel methods to predict and diagnose diseases and to monitor patient therapeutic response. Tears, due to their direct contact with the eye and the fact that lacrimal glands can also be affected by the disease, could give new insights into the mechanisms taking place in thyroid-associated orbitopathy (TAO) and reveal potential promising biomarkers. Tear fluid offers the possibility of the non-invasive acquisition of a sample with a high protein content, thereby attracting continuously growing interest in the discovery of novel biomarkers. This article provides an up-to-date overview of the various putative tear-fluid biomarkers that have been identified. In this review, we present the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases and discuss the future research directions in this area.

MicroRNA Profile Alterations in Parathyroid Carcinoma: Latest Updates and Perspectives.

Simple SummaryDespite the considerable development of diagnostic tools, distinguishing between benign and malignant parathyroid tumors poses a significant diagnostic challenge. Epigenetic regulations, including noncoding microRNAs (miRNAs), have recently emerged as a new and promising source of biomarkers. MiRNAs are post-transcriptional regulators of gene expression. These tissue-specific molecules are known to be deregulated between cancer and normal cells. This review delineates changes in miRNA expression in parathyroid carcinoma (PC), advancing our understanding of PC tumorigenesis and emphasizing, at the same time, that miRNAs can be further exploited for diagnostic and therapeutic purposes.Parathyroid tumors are a genetically heterogenous group with a significant variability in clinical features. Due to a lack of specific signs and symptoms and uncertain histopathological criteria, parathyroid carcinomas (PCs) are challenging to diagnose, both before and after surgery. There is a great interest in searching for accurate molecular biomarkers for early detection, disease monitoring, and clinical management. Due to improvements in molecular pathology, the latest studies have reported that PC tumorigenesis is strongly linked to the epigenetic regulation of gene expression. MicroRNA (miRNA) profiling may serve as a helpful adjunct in distinguishing parathyroid adenoma (PAd) from PC and provide further insight into regulatory pathways involved in PTH release and parathyroid tumorigenesis. So far, only a few studies have attempted to show the miRNA signature for PC, and very few overlaps could be found between these relatively similar studies. A global miRNA downregulation was detected in PC compared with normal glands among differentially expressed miRNAs. This review summarizes changes in miRNA expression in PC and discusses the future research directions in this area.

Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer

BackgroundMajority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC.MethodsWe performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies.ResultsWe identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation.ConclusionsWe identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.

Discovery and function exploration of microRNA-155 as a molecular biomarker for early detection of breast cancer

BackgroundMicroRNA-155 (miR-155) may function as a diagnostic biomarker of breast cancer (BC). Nevertheless, the available evidence is controversial. Therefore, we performed this study to summarize the global predicting role of miR-155 for early detection of BC and preliminarily explore the functional roles of miR-155 in BC.MethodsWe first collected published studies and applied the bivariate meta-analysis model to generate the pooled diagnostic parameters of miR-155 in diagnosing BC such as sensitivity, specificity and area under curve (AUC). Then, we applied function enrichment and protein–protein interactions (PPI) analyses to explore the potential mechanisms of miR-155.ResultsA total of 21 studies were finally included. The results indicated that miR-155 allowed for the discrimination between BC patients and healthy controls with a sensitivity of 0.87 (95% CI 0.78–0.93), specificity of 0.82 (0.72–0.89), and AUC of 0.91 (0.88–0.93). In addition, the overall sensitivity, specificity and AUC for circulating miR-155 were 0.88 (0.76–0.95), 0.83 (0.72–0.90), and 0.92 (0.89–0.94), respectively. Function enrichment analysis revealed several vital ontologies terms and pathways associated with BC occurrence and development. Furthermore, in the PPI network, ten hub genes and two significant modules were identified to be involved in some important pathways associated with the pathogenesis of BC.ConclusionsWe demonstrated that miR-155 has great potential to facilitate accurate BC detection and may serve as a promising diagnostic biomarker for BC. However, well-designed cohort studies and biological experiments should be implemented to confirm the diagnostic value of miR-155 before it can be applied to routine clinical procedures.

Accurate 3-gene-signature for early diagnosis of liposarcoma progression

BackgroundWell- and dedifferentiated liposarcoma (WD/DDLPS) are rare mesenchymal malignant tumors that account for 20% of all sarcomas in adults. The WD form is a low-grade malignancy with a favourable prognosis which may progress to DDLPS, a high-grade aggressive counterpart. WDLPS is referred to as atypical lipomatous tumour (ALT) when localised in extremities, due to its better prognosis. Currently the final differential diagnosis to distinguish between more aggressive and less aggressive form is based on post-surgical histological examination and no molecular biomarkers for early detection are available.MethodsQuantitative polymerase chain reaction (qPCR) analysis of 11 metabolic genes involved in general and adipose tissue-specific metabolism, was performed on ALT (= 8), WDLPS (= 9) and DDLPS (= 20) samples. Subsequent statistical analysis was carried out to determine genes that most accurately can predict DDLPS differential diagnosis. Selected genes were further validated in a separate cohort by qPCR and the data statistically analysed. Deep sequencing was performed on DDLPS specimen from the metastatic patient and on five random WDLPS specimens.ResultsWe established a three-gene signature based on PNPLA2, LIPE and PLIN1, which identified DDLPS with 100% sensitivity and 90% specificity, even in specimens from the WD component of DDLPS tumors. Interestingly, the PNPLA2 gene is deleted in 45% of DDLPS samples analyzed under TCGA project, and the deletion is associated with significantly lower PNPLA2 expression level. However, other mechanisms causing loss or downregulation of the expression of these three genes may be involved. Moreover, the significantly lower level of PNPLA2 is associated with R1 surgical margins, compare to R0 margins, which suggests the more invasive tumor phenotype in the absence of PNPLA2.ConclusionsThe identified metabolic signature allows highly accurate differential diagnosis between WD- and DDLPS even in samples containing lipid droplets, a marker of differentiation, which makes it very suitable for the use on biopsies. In respect to the pathogenesis of the disease, our results give a new insight into possible molecular mechanisms involved and support the recent observation that deletion of PNPLA2 is a novel factor in liposarcoma progression.

Molecular Biomarkers for Early Detection and Prevention of Ovarian Cancer-A Gateway for Good Prognosis: A Narrative Review.

Gynecological cancers are one of the most lethal and deadliest cancers in the world. In India, the prevalence of ovarian cancer accounts for 2.5% to 3%. Despite the availability of improved treatment option along with improved technology, the survival rate of ovarian cancer in the early-stage and the advanced stage is poor. Therefore, due to the heterogeneity of ovarian cancer, to detect it at an early stage and to prevent further mortality turns out to be a big challenge. Researchers are still in the process to identify any single biomarker with good sensitivity and specificity. Various traditional and serum approaches to identify ovarian cancer have been successful in the early stages. The invention of molecular biomarkers such as the use of genomic profiling, DNA methylation, and other approaches have proven to be of higher sensitivity and specificity, which overall affects the prognosis of ovarian cancer. With the use of whole-genome analysis, the detection of possible location of critical tumor suppressor gene (TSGs) in the paired region of chromosomes has been identified, which are associated with BRCA1 and BRCA2 which further makes these novel molecular biomarkers as potential biomarkers. Moreover, studies are required to assess the combined use of traditional, molecular biomarkers that might be useful for enhanced sensitivity and specificity for early detection and prevention of ovarian cancer in early stages which will lead to reduced mortality and good prognosis

Interrelations of Apoptotic and Cellular Senescence Genes Methylation in Inflammatory Bowel Disease Subtypes and Colorectal Carcinoma in Egyptians Patients.

Ras-related domain family member 1 transcript variant A (RASSF1A) controls apoptosis and cell proliferation while p14/ARF gene has a regulatory role in cellular senescence. Failure of apoptosis and cellular senescence occurs during inflammatory bowel disease (IBD) and colorectal cancer (CRC). To reveal the role of peripheral leukocyte promoter methylation of RASSF1A and p14/ARF in the pathogenesis of IBD subtypes and CRC we investigated the methylation state of the two genes by methylation-specific polymerase chain reaction (MSP-PCR) in 60 CRC patients, 60 patients with IBD; 27 with ulcerative colitis and 33 had Crohn's disease and also in 30 healthy subjects. Methylated RASSF1A and p14/ARF genes were detected in 55% and 60% of CRC, while the frequency of the methylated RASSF1A and p14/ARF genes was 23.3% and 43.3% in IBD patients and 3.3% and 13.3% in the control group (P = 0.000 each). Also, the frequency of methylated RASSF1A gene was significantly higher in ulcerative colitis than in Crohn's disease, while a non-significant frequency of methylated p14/ARF was detected between ulcerative colitis and Crohn's disease. Furthermore, methylated RASSF1A and p14/ARF were associated with the grade of CRC but not associated with the age of patients, family history, or tumor location. Results suggest that methylated RASSF1A and p14/ARF are related to CRC and IBD pathogenesis and may be used as molecular biomarkers for early detection of CRC and IBD.

Identification of plasma secreted phosphoprotein 1 as a novel biomarker for upper tract urothelial carcinomas

The key prognostic factor at the time of diagnosis of upper tract urothelial carcinomas (UTUC) is whether the tumor is in the muscle-invasive or non-muscle invasive stage. It is critical to identify novel molecular biomarkers for early detection and target therapy. Plasma proteins secreted by tumor tissues have excellent potential as biomarkers for UTUC. In this study, we conducted a systematic study to identify plasma markers for UTUC based on RNA-seq data from five UTUC tissues and paired adjacent noncancerous mucosa. Through bioinformatics analysis, we found secreted phosphoprotein 1 (SPP1) was the most significant gene that coding secretory protein. Then, qRT-PCR and enzyme-linked immunosorbent assay were performed to evaluate the expression and clinical significance of SPP1 in UTUC. Results found that SPP1 mRNA was upregulated in UTUC cells and tissues, and high SPP1 mRNA expression level was closely related to advanced stage and high grade. Moreover, it is suggested that plasma SPP1 may be a potential biomarker to help identify early-stage UTUC patients and predict invasive and high-grade UTUC. In conclusion, plasma SPP1 is a novel biomarker for UTUC.

The Alz-tau Biomarker for Alzheimer's Disease: Study in a Caucasian Population.

The establishment of a molecular biomarker for early detection of Alzheimer's disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer's clinic. The changes in hyperphosphorylated tau and amyloid peptide in the cerebrospinal fluid is currently used as a tool in the clinics and for research purposes, but this method is highly invasive. Recently, we reported a non-invasive and reliable blood biomarker that correlates the increase in the ratio of heavy tau (HMWtau) and the low molecular weight tau (LMWtau) in human platelets and the decrease in the brain volume as measured by structural MRI. This molecular marker has been named Alz-tau®. Beyond the clinical trials developed with a Latin American population, the present study focuses on an evaluation of this biomarker in a Caucasian population. We examined 36 AD patients and 15 cognitively normal subjects recruited in Barcelona, Spain. Tau levels in platelets were determined by immunoreactivity and the cognitive status by using GDS and MMSE neuropsychological tests. The HMW/LMW tau ratio was statistically different between controls and AD patients. A high correlation was found between the increase in MMSE scores and HMW/LMW tau ratio. This study showed that this ratio is significantly higher in AD patients than controls. Moreover, this study on a peripheral marker of AD is valuable to understanding the AD pathogenesis.

Clinical importance of microtubule-associated protein 1 light chain 3 and mammalian target of rapamycin expression in oral leukoplakia and oral squamous cell carcinoma

This study aimed to investigate the expression and relationship of microtubule-associated protein 1 light chain 3 (LC3) and mammalian target of rapamycin (mTOR) in normal oral mucosa, oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC). This work also analyzed the relationship between expression levels and clinical factors. This study evaluated the clinical value of LC3B and mTOR as indices to determine the carcinogenic potential of OLK. Immunohistochemistry was used to detect the expression of LC3B and mTOR in 20 cases of normal oral mucosa, 120 cases of OLK, and 30 cases of OSCC. The clinical data of 120 patients with OLK were analyzed. The relationships between expression levels and clinical factors were investigated. In normal oral mucosa, OLK and OSCC, the positive rates of LC3B expression were 85.0%, 65.8% and 33.3% (P<0.05), whereas the positive rates of mTOR expression were 20.0%, 48.3% and 76.7% (P<0.05). The expression levels of LC3B and mTOR were correlated and related to clinical typing of OLK (P<0.05). LC3B and mTOR can be used as molecular biomarkers for early detection of OLK.

Significance of molecular biomarkers in idiopathic pulmonary fibrosis: A mini review.

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible condition with poor prognosis that is characterized by a variable clinical course in each patient, which renders it a complex disease with unknown causes. Despite the proven efficacy of novel antifibrotic therapies, including pirfenidone and nintedanib, the diagnosis and follow-up of IPF remain challenging. Hence, the identification of molecular biomarkers for early detection of IPF and to predict biologically determined individual clinical courses, has recently piqued the interest of researchers. Previous studies have demonstrated the diagnostic and prognostic efficacy of blood proteins such as KL-6, Surfactant protein (SP)-A, and SP-D, in patients with IPF. Due to their use in clinical practice in Japan, for approximately twenty years, a significant amount of data about these biomarkers has been accumulated. This paper reviews the recent literature on molecular biomarkers for IPF that have been developed in Japan as well as other potential molecular biomarkers.

Abstract 5535: C-EDRN and US-EDRN collaboration on systematic review and meta-analysis of the association between RAD51 135G/C genetic biomarker and cancer risk

Abstract Introduction: The Early Detection Research Network (EDRN) is an initiative of the National Cancer Institute (NCI) to support the translation of biomarker research into clinical applications. The US-EDRN and China-EDRN (C-EDRN), led by CICAMS, China, have strong collaborations on discovering and validating molecular biomarkers for early detection, diagnosis, and prevention. Our collaboration projects promote scientific exchanges, visiting scientists, biomarker discoveries and validations, as well as system review. Here, we report the system review of a genetic marker, RAD51 135G/C polymorphism and cancer risk. Background: The RAD51 gene is essential for the repair of damaged DNA related to tumor development. Although some studies have investigated the association between RAD51135G/C polymorphism and the risk of different cancers, the results are conflicting rather than conclusive. Therefore, it is necessary to further perform the system review of the polymorphism related to cancer risk. Method: The PubMed, Embase, and Cochrane library databases were searched to identify eligible studies that were published in English up to July 2017. Two investigators independently screened, extracted the data, and evaluated the quality of all eligible studies using Newcastle-Ottawa Scale (NOS). Crude odds ratios (ORs) together with their corresponding 95% confidence interval (CI) were calculated to assess the strength of association under dominant and recessive models. Subgroup analyses were performed based on ethnicity and cancers. Begg's test was used to measure publication bias. Result: A total of 75 studies from 71 articles were finally qualified and enrolled in this meta-analysis. The publication year of selected studies ranged from 2002 to 2017. The pooled results involving 24,284 cases and 27,649 controls showed that RAD51 polymorphism was associated with increased cancer risk under both dominant and recessive models. In subgroup analysis, the association varied among different ethnicities and cancers. Significantly elevated cancer risk was observed in Caucasians under both models, and in Asians under dominant model. Breast cancer, hematologic malignances, ovarian cancer, endometrial cancer, prostate cancer also showed significant associations with RAD51 polymorphism. Begg's test results showed there were no publication bias in the study. Conclusion: This meta-analysis indicated that the RAD51135G/C polymorphism was significantly associated with the susceptibility of cancer and it may be utilized as a valuable biomarker in early diagnostics and risk assessment. Further efforts are needed to identify and validate this finding in prospective studies and to explore the potential function of the variants in different cancers for clinical applications. Citation Format: Run Chen, Wendy Wang, Wenqiang Wei, Sudhir Srivastava, Jie He. C-EDRN and US-EDRN collaboration on systematic review and meta-analysis of the association between RAD51 135G/C genetic biomarker and cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5535.

Detection of some microRNAs expressions in tissues of British Women diagnosed with Breast cancer

MicroRNAs (miRNAs) are small, non coding RNA, found to play critical roles in tumor progression. The aim of this project was to investigate the expression of miR-21, miR-26b, miR-429 and miR-378 in human breast cancer tissues. By using TaqMan qRT-PCR assay to detect the expression of these selected miRNAs in 12 pairs of breast cancer tissues and their corresponding noncancerous breast tissues. Data indicated that the relative level of miR-21 was up regulated in cancer tissues (p 0.0014), miR-26b was significantly down regulated in breast cancer tissues (p 0.0017), While the novel expression of miR-429 was significantly up regulated in breast cancer tissues (p 0.0131) and novel down expression of miR-378 in breast cancer tissues (p 0.0006). These microRNAs might be a potential molecular biomarker for early detection of breast cancer in women

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease.

Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis.

Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma

DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ −0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2′-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P < 0.05) were observed when expression levels of STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.

Clinicopathological features associated to MiRNA-195 expression in patients with breast cancer: Evidence of a potential biomarker.

Background & Objective:MiRNAs are a systematic class of small non-coding RNAs with impending role as tumor biomarkers. Our objective was to identify the level of expression of Mir-195 in patients with breast cancer along with its correlation with clinicopathologic features.Methods:A total of 209 females in which 139 histologically diagnosed breast cancer (BC) cases and 70 healthy controls matched for age, their relative clinical and histopathological findings were recorded from their laboratory reports and hospital record of the patients. Plasma was used for extraction of total RNA and cDNA was prepared by using both miR-195 stem loop RT primers and gene specific antisense primers while U6 IT was used as control. Quantitative real-time PCR (qRT-PCR) for miR-195 expression status was performed and amplification (down regulation) was recorded.Results:Of 139 samples the expression of miR-195 was down regulated in 72.6% cases and the remaining 27.3% cases behaved same as 70 healthy or normal controls. Significant correlation of low miR-195 expression with higher differentiation grade, lymph node metastasis and clinical stage was found.Conclusion:Significant correlation between miR-195 expression and some clinicopathological features were recognized. MiR-195 could be used as potential non-invasive, molecular biomarker for early detection of breast cancer.