SMAD4 (SMAD family member 4)

These findings demonstrated that codon-specific KRAS mutations affect PDAC outcomes differently based on disease stage at diagnosis. As studies testing KRAS inhibitors continue to emerge and mature, the prognostic variability of individual KRAS mutations must be carefully considered to avoid confounding and ensure accurate evaluation of therapeutic efficacy in early-phase studies.

Although many syndromes mimic HHT, few combine mucosal telangiectasias, high-flow AVMs, and recurrent hemorrhage. Integrating clinical, imaging, and genetic data enables precise diagnosis, risk stratification, and personalized management.

Critically, low-concentration RSV enhanced both proliferation and differentiation, while high-concentration RSV inhibited differentiation independently of Smad4. This study provided the first in vivo evidence at the whole-organism level that RSV concentration dictated divergent stem cell differentiation fates, offering a scientific basis for its rational evaluation and application.

Mechanistically, COMP shifted transforming growth factor beta (TGFβ) signaling from canonical phosphorylated mothers against decapentaplegic homolog 2/3 (pSMAD2/3) activation toward pSMAD1/5, likely through its interaction with PMEPA1. This study suggests the COMP-PMEPA1 axis as a new driver of EMT in breast cancer models.

Our results establish SMAD4 SUMOylation as a pivotal molecular switch in lens fibrosis pathogenesis. Employing inhibitory drugs of SUMO conjugation in the years to come has the potential to be a novel therapeutic strategy for fibrotic cataracts.

Our data indicated that NRG1-SMAD4-miR-5010-5p was the most prominent sub-network motif engaged in NSCLC patients based on the degree of centrality. In vitro mechanistic studies will provide better understanding on the role of NRG1-SMAD4-miR-5010-5p motif in NSCLC cases.

This experience also shows that SETD2 functional impairment may underlie gILC hypermutation, while HNF1B overexpression could contributes to a glycogen-rich clear cytoplasm. Overall, this case emphasizes the complexity of MDL with gILC, and highlights the need for further studies to clarify the underlying molecular mechanisms and their prognostic implications.

The frequency of TMB-high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI-H plus TMB-high while also exhibiting some efficacy in patients with MSS plus TMB-high.

Therapy using miRNA mimics and inhibitors aims to restore gene expression balance, but delivery and stability concerns persist. Advances in nanotechnology are enabling increasingly targeted and effective miRNA-based therapies, potentially transforming the clinical management of pancreatic cancer (PC).

Integrated clinical, genomic, and histopathological analyses revealed a high frequency of lymph node-negative, intraductal papillary mucinous neoplasm (IPMN)-associated cancers, KRAS and/or SMAD4 wild-type tumors, and classical subtype by immunohistochemistry, all collectively associated with more favorable outcomes. Acknowledging the highly selected nature of this cohort, isolated intrapancreatic metastases demonstrate a more indolent biology and these patients may benefit from personalized management approaches beyond traditional paradigms.

Molecular alterations in KRAS, TP53, BRCA1/2, and others may aid in diagnosis, prognostication, and the selection of targeted therapeutic options. By systematically integrating clinicoradiologic, cytological, histological, immunophenotypic, and molecular data, pathologists can effectively differentiate PDAC from benign or reactive lesions and metastatic neoplasms, ensuring accurate diagnoses that are essential for optimal patient management.

A high CAF-signature and SMAD4 mutations have prognostic value for recurrence both in MSS CC and in MRD, indicating potential predictive value for response to ACT. This molecular profile provides leads to design novel therapies for patients resistant to standard ACT.