1,721,266 research outputs found
Dissecting the transcriptome of CD44 in triple negative breast cancer
Full text linkThe CD44 receptor is a transmembrane glycoprotein involved in the recognition of specific extracellular matrix (ECM) ligands. It has a complex transcriptional regulation characterized by different splicing variants, many of which play a role in promoting tumorigenesis. Therefore, CD44 variants may serve as prognostic biomarkers and therapeutic targets. Triple-negative breast cancer (TNBC) is a poor prognosis subtype of breast adenocarcinomas characterized by the lack of druggable molecular hallmarks. TNBC represents a prototypical model for studying CD44's pro-tumoral activity. However, the regulation of the CD44 transcriptome and its influence on TNBC aggressiveness remains elusive.In this study, we dissected the CD44 transcriptome in the TNBC cell lines MDA-MB-231 and MDA-MB-468, which exhibit different malignant properties. MDA-MB-231 cells display higher extracellular matrix invasive potential, more prominent metastatic potential, and poorer response to chemotherapy compared to MDA-MB-468 cells. Finally, we induced the overexpression of a differentially expressed CD44 isoform between the two cell lines using transfection assays. We then performed whole transcriptome RNA-sequencing analysis of the transfected cells and their control. We identified distinct patterns in the CD44 transcriptome between the two TNBC cell lines. Specifically, among the top 5 differentially expressed (DE) CD44 isoforms compared to the control cell line, we detected the predicted transcript variant XM_017018585.2. This variant will be further confirmed through PCR and Sanger sequencing assays. To functionally characterize XM_017018585.2, we performed overexpression of the exogenous transcript in the MDA-MB-468 cell line using viral transfection. The overexpression of XM_017018585.2 induced upregulation of transcripts involved in the MAPK8 signaling pathway and downregulation of interferon response programs. Interestingly, the same downregulated genes were also observed in the estrogen-responsive breast cancer cell line MCF-7 upon silencing of specific pathways.The CD44 transcriptome analysis of TNBC cell models revealed novel transcriptional variants with potential significance in the modulation of the malignant phenotype. This study could shed light on the role of previously unidentified CD44 isoforms in promoting tumorigenesis. Furthermore, it could uncover new candidate diagnostic and prognostic biomarkers based on CD44 variant expression
Biomarker testing in patients with advanced non-small cell lung cancer: the never-ending story
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Next-generation sequencing for PTEN testing in HR+/HER2˗ metastatic breast cancer
No full text: Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are key drivers of tumorigenesis and progression in hormone receptor-positive, HER2-negative (HR+/HER2 -) metastatic breast cancer (MBC). These genomic changes are actionable through targeted therapeutic agents. In particular, access to these therapies depends on accurate molecular testing of PIK3CA, AKT1, and PTEN. Next-generation sequencing (NGS) has emerged as a transformative diagnostic tool, offering a comprehensive analysis of PI3K pathway alterations while concurrently evaluating other actionable markers, such as ESR1 and BRCA. Acknowledging its clinical importance, the European Society for Medical Oncology (ESMO) recommends NGS of tumor or plasma samples as the standard of care for patients with HR+ /HER2 - MBC. Although resource-intensive, NGS represents a significant advancement in MBC diagnostics, ensuring that therapeutic decisions are informed by a detailed and multidimensional molecular profile. This review highlights the capabilities of NGS for PI3K pathway testing in HR+ /HER2 - MBC, with a particular focus on the spectrum of PTEN alterations
Editorial: Molecular pathology and computational image analyses in gynecologic malignancies
No full textComments on roles of circulating tumor cells in the metastatic cascade and tumor immune escape: biology and clinical translation
No full textLiquid Biopsy and Lung Cancer
No full textThe identification of non-small cell lung cancer (NSCLC) patients potentially responsive to targeted therapies relies on a number of relevant biomarkers, including EGFR, ALK, ROS-1, and PD-L1. Biomarker identification is most commonly based on surgical sample collection. However, when tissues are difficult to reach or when multiple analyses are necessary to monitor tumor progression and treatment response, liquid biopsy is a valid noninvasive alternative. This analysis, which is preferentially performed on circulating tumor DNA (ctDNA) extracted from plasma samples, has the major advantage of reducing the inherent risks and discomfort of tissue biopsy. However, a major disadvantage is that it yields only a low number of ctDNA targets. Thus, to avoid false-positive and false-negative results, it is important to adopt and validate technologies with high sensitivity and specificity in the pre-analytical phase of sampling. This review succinctly addresses the principal methodologies for analyzing plasma-derived ctDNA in NSCLC patients
Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration
No full text: Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages. The International Society of Liquid Biopsy (ISLB) has addressed these challenges by forming a Quality Control and Accreditation Committee, focused on developing frameworks for pre-analytical, analytical, and interpretive processes. Key priorities include mitigating pre-analytical variability with stringent guidelines for blood handling and ensuring adherence to international standards like ISO 15189 and CLIA/CAP. ISLB emphasizes harmonized methodologies, with advanced techniques like droplet digital PCR and next-generation sequencing requiring unified workflows. Collaboration with global initiatives, including the European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), and International Liquid Biopsy Standardization Alliance (ILSA), supports the validation of ctDNA testing. These efforts are vital for integrating LB into clinical care, advancing precision oncology, and improving patient outcomes through reliable and standardized applications
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