Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells

Conditioned medium (CM) from clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with differing invasive abilities, were examined for their effect on in vitro invasion. Conditioned medium from Clone #3 (CM#3) strongly promoted invasion, while CM from Clone #8 (CM#8) inhibited invasion in vitro. 2D DIGE followed by MALDI-TOF MS analysis of CM#3 and CM#8 identified 41 proteins which were differentially regulated; 27 proteins were down-regulated and 14 proteins up-regulated in the invasion-promoting CM#3 when compared to CM#8. Western blotting analysis confirmed the down-regulated expression of gelsolin and the up-regulation of aldehyde dehydrogenase 1A1 in CM#3. Down-regulation of aldehyde dehydrogenase 1A1 in Clone #3 CM and gelsolin levels in Clone #8 CM by siRNA transfection revealed an important involvement of these proteins in promoting and inhibiting invasion in these pancreatic cancer cell lines

Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

Cell

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n\ua0= 151) and plasma-derived (n\ua0= 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.U54 CA163120/CA/NCI NIH HHS/United StatesU54 CA163117/CA/NCI NIH HHS/United StatesR01 CA218513/CA/NCI NIH HHS/United StatesU19 OH009077/OH/NIOSH CDC HHS/United StatesU19 AI144301/AI/NIAID NIH HHS/United StatesP30 CA008748/CA/NCI NIH HHS/United StatesUL1 TR002384/TR/NCATS NIH HHS/United StatesU01 CA210240/CA/NCI NIH HHS/United StatesR35 CA232093/CA/NCI NIH HHS/United StatesR01 CA207983/CA/NCI NIH HHS/United StatesR50 CA211462/CA/NCI NIH HHS/United StatesS10 RR027699/RR/NCRR NIH HHS/United StatesR01 CA169416/CA/NCI NIH HHS/United StatesU01 CA169538/CA/NCI NIH HHS/United StatesU01 CA224175/CA/NCI NIH HHS/United States2021-08-20T00:00:00Z32795414PMC75227668412vault:3603

Omics approaches in pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal—around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients

Biomarkers for Cancer: A Detail Review

When aberrant cells multiply uncontrolled, transcend their normal borders, invade nearby tissues, or spread to other organs, a wide spectrum of illnesses collectively referred to as "cancer" can arise in practically every organ or tissue of the body. The second-leading cause of death globally in 2018, cancer was expected to be responsible for 9.6 million deaths, or one in every six fatalities. A cancer biomarker is a characteristic that can be used to gauge a patient's likelihood of developing cancer or its outcome. Various biomarkers can be used at molecular and cellular level. It is crucial that biomarkers undergo thorough review, including analytical validation, clinical validation, and appraisal of clinical value, prior to being included into normal clinical treatment because of the crucial role they play at all stages of disease. We discuss important steps in the creation of biomarkers in this review, including how to prevent introducing bias and standards to adhere to when presenting the findings of biomarker research

Exosomes: Novel Biomarkers for Clinical Diagnosis

Exosomes are 30–120 nm endocytic membrane-derived vesicles that participate in cell-to-cell communication and protein and RNA delivery. Exosomes harbor a variety of proteins, nucleic acids, and lipids and are present in many and perhaps all bodily fluids. A significant body of literature has demonstrated that molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), hold great promise as novel biomarkers for clinical diagnosis. In this minireview, we summarize recent advances in the research of exosomal biomarkers and their potential application in clinical diagnostics. We also provide a brief overview of the formation, function, and isolation of exosomes

Salivary Diagnostics

Saliva is one of the most ideal diagnostic tools. It is inexpensive, noninvasive, and easy to use. Other advantages like ease of collection and minimal patient discomfort make it more acceptable to the patient as well as the clinician. The most challenging aspect in salivary diagnostics is to identify the biomarker that is linked to a disease. Researches are also ongoing to develop a device that can have reliable and valid clinical applications. This chapter briefly discusses the background and current scope of salivary diagnostics, technologies for the discovery of biomarkers along with a summary of salivary sample collection, and processing methods

Integrative Genomic Data Mining for Discovery of Potential Blood-Borne Biomarkers for Early Diagnosis of Cancer

Background: With the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA) program to identify potential blood-based markers for six common human cancer types. Methodology/Principal Findings: In the Oncomine platform, the genes overexpressed in cancer tissues relative to their corresponding normal tissues were filtered by Gene Ontology keywords, with the extracellular environment stipulated and a corrected Q value (false discovery rate) cut-off implemented. The identified genes were imported to the IPA biomarker module to separate out those genes encoding putative secreted or cell-surface proteins as blood-borne (blood/serum/plasma) cancer markers. The filtered potential indicators were ranked and prioritized according to normalized absolute Student t values. The retrieval of numerous marker genes that are already clinically useful or under active investigation confirmed the effectiveness of our mining strategy. To identify the biomarkers that are unique for each cancer type, the upregulated marker genes that are in common between each two tumor types across the six human tumors were also analyzed by the IPA biomarker comparison function. Conclusion/Significance: The upregulated marker genes shared among the six cancer types may serve as a molecular tool to complement histopathologic examination, and the combination of the commonly upregulated and unique biomarkers may serve as differentiating markers for a specific cancer. This approach will be increasingly useful to discover diagnostic signatures as the mass of microarray data continues to grow in the ‘omics’ era

Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches