ITGB3 (Integrin Subunit Beta 3)

The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets.

Here, we found that exosomes secreted by lung cancer cells that had acquired epidermal growth factor receptor tyrosine kinase inhibitor resistance and undergone epithelial-mesenchymal transition (osimertinib- and WZ4002-resistant H1975) exhibited enhanced brain-specific distribution and a concomitant increase in BrM compared with exosomes from parental H1975 cells. Clinically, exosomal L1CAM demonstrated diagnostic potential for BrM (area under the curve &lsqb;AUC] = 0.80), and a combined exosomal L1CAM/ITGB3 panel significantly improved diagnostic accuracy (AUC = 0.98). Collectively, these findings identify exosomal L1CAM as a key regulator of brain-specific metastasis and support the clinical utility of the L1CAM/ITGB3 panel as a noninvasive biomarker for BrM in lung cancer.

Furthermore, risk models incorporating specific protein signatures effectively stratified patients by platinum sensitivity/resistance (9-protein panel: ILK, CDCP1, CD86, CLDN4, CLEC1B, CDHR5, CLDN11, JAM2, FOLH1), lymph node metastasis status (7-protein panel: APOE, CD28, CLDN4, FOLH1, ITGAL, JAML, ULBP3), and post-surgical residual disease burden (4-protein panel: CD44, CLMP, ITGA4, AMIGO1), with Cluster 13 (ITGB1-high) also significantly associated with residual disease. This work demonstrates the power of single-EV proteomics combined with machine learning for non-invasive diagnosis and clinical outcome assessment in advanced ovarian cancer, though the absence of early-stage patients limits its applicability for early detection.

Functional enrichment and protein-protein interaction analyses revealed that CTSC regulates the ECM-integrin-PI3K-Akt signaling pathway, contributing to tumor cell proliferation and survival. The findings establish a multi-omics-based biomarker panel with strong diagnostic utility and mechanistic relevance, suggesting a potential framework for future translational validation in clinical cohorts.

CP-GEP demonstrated good prognostic performance, particularly for patients with pT1b-pT2a melanoma and thus could be considered a noninvasive alternative for a SLNB.

The LNMRGS is a robust prognostic signature for CRC. NPR3 plays a key role in metastatic progression and chemoresistance, suggesting it as a potential therapeutic target.

The remodeled microenvironment in turn facilitates epithelial-mesenchymal transition (EMT) and angiogenesis, thereby promoting CRC progression and metastasis. Our findings thus delineate the ANGPTL3-integrin αVβ3-STAT3-COL1A2 axis as a central driver of CRC metastasis, nominating ANGPTL3 as both prognostic biomarker for metastatic risk stratification and therapeutic target amenable to molecular intervention in CRC management.

Given USP7's role in oxidative stress and ferroptosis, we examined its involvement and found that P5091 induced ferroptosis via reactive oxygen species (ROS) elevation, glutathione peroxidase 4 (GPX4) downregulation, and elevated lipid peroxidation. These findings demonstrate that USP7 inhibition by P5091 enhances PLX4032 efficacy by promoting tumor suppression and ferroptosis in BRAFV600E-mutant thyroid cancer, offering a promising strategy to overcome resistance.

P=N/A, N=200, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

Additionally, ferroptosis induction via radiotherapy, natural compounds (solasodine, luteolin), repurposed drugs (disulfiram/copper), or nanotechnology synergizes with immunotherapy by promoting lipid peroxidation and reversing EBV-mediated immune evasion. Targeting ferroptosis regulators (SLC7A11, GPX4, FTO, CD38) overcomes resistance, positioning ferroptosis modulation as a transformative strategy for NPC management.

This study identifies miRNAs and their target genes as critical regulators of inflammation in COPD, MS, and lung cancer. Single-cell insights and pathway enrichment provide a comprehensive view of shared molecular mechanisms, contributing to biomarker discovery and therapeutic strategies for precision medicine in inflammatory diseases.