ADGRG6 (Adhesion G Protein-Coupled Receptor G6)

ADGRG6 functions as an oncogenic driver in PAAD, promoting tumor progression and fostering an immunosuppressive microenvironment via NF-κB/STAT6 signaling. These findings not only broaden the mechanistic understanding of ADGRG6 function but also suggest it as a promising target for therapeutic intervention in PAAD.

The identification of TRAPM and the RC3 subtype enhances our understanding of BC heterogeneity and highlights potential therapeutic targets. This study provides a foundation for personalized treatment strategies by clarifying the biological significance and clinical relevance of the RC3 subtype.

MAFs were not associated with any clinical and demographic features (p > 0.05), with the only exception being the tumor size: patients with tumors larger than 2.16 cm3 had higher MAFs than the rest (23.4 [1.8; 46.3] vs. 1.6 [0; 24.6] %, respectively, p = 0.02). Upon further validation, the presented tumor DNA detection panel for ddPCR might become a useful tool for diagnostic purposes in UBC.

A cancer-associated CUB domain mutant, C94Y, drastically perturbs the ECR conformation and results in elevated signaling, whereas another CUB mutant located near a conserved Ca2+-binding site, Y96A, decreases signaling. Our results suggest an ECR-mediated mechanism for ADGRG6 regulation in which the CUB domain instructs conformational changes within the ECR to regulate receptor signaling.

In three cohorts, ADGRG6 predicted favorable anti-PD-1 responses (AUC: 0.601-0.814). This study establishes ADGRG6 as a cancer-type-specific oncogene and independent prognostic marker for BRCA/LGG, proposing its targeting combined with immunotherapy as a novel approach to enhance cancer treatment efficacy.

These findings underscore the potential of cfDNA biomarkers to enhance BC detection and reduce the rate of unnecessary biopsies.

Hotspot mutation is promising biomarker to predict earlier recurrence than CT-scan. Multiple detection of mutations in cfDNA contributes to reliable recurrence prediction.

Furthermore, subcutaneous xenograft experiments in mice demonstrated that ADGRG6 knockdown substantially suppressed the growth of engrafted PAAD tumors. ADGRG6 may serve as a novel prognostic marker and a therapeutic targets for PAAD, playing a crucial role in the proliferation, metastasis, and immune marker regulation of PAAD through elevating protein level of mutated p53.

TBC1D12 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, p = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, p = 0.010), and advanced tumor stages (85.7% vs. 32.5%, p = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of TBC1D12 5'UTR mutations in ATC and indicated an association between TBC1D12 mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.

The mutant allele "C" and mutant genotype "CA" of rs11155242 act as protective genetic factors against COPD susceptibility. This study will provide a new research direction for the personalized prevention and treatment of COPD in the elderly Han population in southern China, and lay a potential scientific basis.

We discuss challenges in hit identification, target validation, and drug discovery, highlighting molecular compositions and recent structural breakthroughs. ADGRG ligands can offer new insights into aGPCR modulation and have significant potential for novel therapeutic interventions targeting various diseases.

P=N/A, N=301, Completed, Uludag University