AGR2 (Anterior gradient 2)

In vivo, rAGR2 accelerated tumor growth in melanoma and lung cancer models, accompanied by increased TAM accumulation, a shift toward M2 polarization, and suppressed T-cell function. AGR2 drives tumor progression by reprogramming TAMs toward an M2 phenotype and attenuating T-cell function via the CD98hc-xCT/p-ERK pathway, highlighting its potential as both a prognostic marker and a therapeutic target.

Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with AGR2, NANOG, OCT4, and SOX2, miR-150 and miR-128. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor-OED.

Our findings provide novel diagnostic and prognostic biomarker candidates and insights into mechanisms driving EOC progression with histotype- and stage-specificity. This may aid the development of improved clinical tools for detection, patient stratification, and targeted therapies in EOC.

Our study identified specific proteins as potential NMIBC biomarkers and drug targets. The identified proteins, particularly those linked to tumor recurrence and staging, warrant further validation to assess their clinical utility in NMIBC diagnosis, prognosis, and treatment strategies.

This proof-of-concept study demonstrates that a machine learning-assisted multiplex autoantibody assay offers a feasible noninvasive approach for CMT detection. Further validation in larger, independent cohorts is warranted to support clinical translation in veterinary oncology.

The clinical validity of the multi-platform was confirmed by recoveries of over 95% in human serum samples and by ELISA. In this study, low-cost electrochemical panel systems that enable the simultaneous determination of AGR2, GLY, FOLR1, and SMRP biomarkers with high selectivity and accuracy, a wide linear range (1-500 pg mL⁻¹), low detection limits, and good reproducibility were produced for the first time.

These results highlight the potential of network-informed machine learning to identify subtle proteomic patterns and pathway-level dysregulation prior to clinical diagnosis. This proof-of-concept study supports further development of GNN approaches for early ovarian cancer detection and warrants validation in larger, independent cohorts.

Therapeutically, administration of an AGR2-targeting peptide synergizes with ferroptosis inducers, significantly enhancing cell death in PDAC models. Our findings not only elucidate a novel AGR2/p53/FPN1 regulatory axis in ferroptosis control but also propose innovative combination strategies for pancreatic cancer treatment.

Our findings uncover a mechanistic basis for EGFR inhibitor resistance of CDK4 and CDK6 amplified EGFR-mutant LUAD. They also provide a rationale for the biomarker-driven clinical development of combination EGFR and CDK4/6-targeted therapies for the treatment of a subset of EGFR-mutant LUAD patients.

Innovative strategies that integrate stromal-targeting agents, complement modulators, anti-CLDN18.2 antibodies, and novel GRIN2D-targeted therapies, along with precision molecular profiling, offer potential for enhancing patient outcomes. Tailored approaches that incorporate early detection and dynamic biomarker monitoring may ultimately transform GSRCC management toward personalized, evidence-based therapies and prevention.

Additionally, multivariate analysis indicated that the positive expression of MACC1, AGR2, and KAI1, alongside tumor stage and LNM stage, could serve as independent prognostic indicators for OS in individuals diagnosed with cervical squamous cell carcinoma. MACC1, AGR2, and KAI1 may represent potential metastatic and prognostic biomarkers, as well as promising therapeutic targets for squamous cell carcinoma of the cervix.

Our differential gene and signaling pathway analysis revealed the potential tumor-promoting mechanisms. These insights may offer new perspectives for clinical strategies targeting macrophages or the tumor microenvironment to treat brain metastasis of lung cancer.