Colorectal cancer is one of the most common cancers around the world, which is a severe threat to people's health. SMAD4 belongs to the dwarfin/SMAD family, which plays a crucial role in TGF-β and BMP signal pathways. As the molecular characterization of colon cancer patients following SMAD4 mutations remains unclear, we integrated multi-omics data of SMAD4 mutant patients to reveal the profile of molecular characterization of SMAD4 mutation. A missense mutation is the most common mutant type of SMAD4. Patients with SMAD4 mutation had worse survival. Tumor tissues from patients carrying the SMAD4 mutation showed a reduction in various immune cells, such as CD4 + memory T cells and memory B cells. Many differential genes were identified compared to the SMAD4 mutation-free group and could be significantly enriched for tumor- and immune-related signaling pathways. In addition, the mutant group had different drug sensitivities than the non-mutant group.
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http://dx.doi.org/10.1007/s12672-024-01268-7 | DOI Listing |
Cancer Res
January 2025
University of Cambridge, Cambridge, United Kingdom.
Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing to the dismal prognosis associated with this cancer. Evidence suggests that PDAC stromal composition is shaped by mutations within malignant cells, but most previous work has focused on pre-clinical models driven by KrasG12D and mutant Trp53. Elucidation of the contribution of additional known oncogenic drivers, including KrasG12V mutation and Smad4 loss, is needed to increase understanding of malignant cell-stroma crosstalk in PDAC.
View Article and Find Full Text PDFJ Hepatol
January 2025
Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Background & Aims: Papillary neoplasms of the biliary tree, including intraductal papillary neoplasms (IPN) and intracholecystic papillary neoplasms (ICPN), are recognized as precancerous lesions. However, the genetic characteristics underlying sequential carcinogenesis remain unclear.
Methods: Whole-exome sequencing was performed on 166 neoplasms (33 intrahepatic IPNs, 44 extrahepatic IPNs, and 89 ICPNs), and 41 associated carcinomas.
Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder caused by mutations in the bone morphogenetic protein signaling pathway, leading to arteriovenous malformations. While previously thought to share molecular and cellular dysregulation, this study reveals highly distinct mechanisms depending on whether mutations occur in Alk1 or SMAD4. Loss of SMAD4 enhances endothelial cell responses to flow, including flow-regulated transcription and cell migration against blood flow, causing excessive pruning of capillaries and the formation of single large shunts.
View Article and Find Full Text PDFWorld J Gastrointest Oncol
January 2025
Department of Medical College, Jinan University, Guangzhou 510000, Guangdong Province, China.
Background: Gallbladder neuroendocrine carcinoma (NEC) represents a subtype of gallbladder malignancies characterized by a low incidence, aggressive nature, and poor prognosis. Despite its clinical severity, the genetic alterations, mechanisms, and signaling pathways underlying gallbladder NEC remain unclear.
Case Summary: This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient, who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.
J Gastrointest Oncol
December 2024
Department of Traditional Chinese Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, with a rising incidence observed in younger demographics. Despite surgical resection remaining the cornerstone of treatment, metastatic CRC poses significant therapeutic challenges. Immunotherapy, a mode of treatment that leverages the patient's immune system, presents a promising frontier in CRC management, particularly for late-stage cases with limited treatment options.
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