NPJ Precis Oncol
Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, 261053, Weifang, Shandong, China.
Published: June 2022
Immune checkpoint inhibitors (ICIs) are most commonly used for melanoma and non-small cell lung cancer (NSCLC) patients. FAT atypical cadherin 1 (FAT1), which frequently mutates in melanoma and NSCLC. In this study, we aim to investigate the association of FAT1 mutations with ICI response and outcome. We collected somatic mutation profiles and clinical information from ICI-treated 631 melanoma and 109 NSCLC samples, respectively. For validation, a pan-cancer cohort with 1661 patients in an immunotherapy setting was also used. Melanoma and NSCLC samples from the Cancer Genome Atlas were used to evaluate the potential immunologic mechanisms of FAT1 mutations. In melanoma, patients with FAT1 mutations had a significantly improved survival outcome than those wild-type patients (HR: 0.67, 95% CI: 0.46-0.97, P = 0.033). An elevated ICI response rate also appeared in FAT1-mutated patients (43.2% vs. 29.2%, P = 0.032). Associations of FAT1 mutations with improved prognosis and ICI response were confirmed in NSCLC patients. In the pan-cancer cohort, the association between FAT1 mutations and favorable ICI outcome was further validated (HR: 0.74, 95% CI: 0.58-0.96, P = 0.022). Genomic and immunologic analysis showed that a high mutational burden, increased infiltration of immune-response cells, decreased infiltration of immune-suppressive cells, interferon and cell cycle-related pathways were enriched in patients with FAT1 mutations. Our study revealed that FAT1 mutations were associated with better immunogenicity and ICI efficacy, which may be considered as a biomarker for selecting patients to receive immunotherapy.
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http://dx.doi.org/10.1038/s41698-022-00292-6 | DOI Listing |
Int J Biol Sci
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China.
FAT atypical cadherin 1 (), which encodes an atypical cadherin-coding protein, has a high mutation rate and is commonly regarded as a tumor suppressor gene in head and neck squamous cell carcinoma (HNSCC). Nonetheless, the potential regulatory mechanisms by which FAT1 influences the progression of HNSCC remain unresolved. In this context, we reported that FAT1 was downregulated in tumor tissues/cells compared with normal tissues/cells and that it was correlated with the clinicopathological features and prognosis of HNSCC.
View Article and Find Full Text PDFOncol Lett
March 2025
Department of Hematology, Shengli Oilfield Central Hospital, Dongying, Shandong 257000, P.R. China.
The FAT atypical cadherin 1 (FAT1) gene is the ortholog of the fat gene and encodes the protocadherin FAT1. FAT1 belongs to the cadherin superfamily, a group of full-length membrane proteins that contain cadherin-like repeats. In various types of human cancer, FAT1 is one of the most commonly mutated genes, and is considered to be an emerging cancer biomarker and a potential target for novel therapies.
View Article and Find Full Text PDFMod Pathol
December 2024
Department of Anaesthesia and Intensive Care Medicine, 3(rd) Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
Penile squamous cell carcinoma (pSCC) represents an uncommon malignancy characterized by stagnant mortality, psychosexual distress, and a highly variable prognosis. Currently, the WHO distinguishes between human papillomavirus (HPV) related and HPV independent pSCC. Recently, there has been an evolving line of research documenting the enrichment of HPV-independent pSCC with a high tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression, as well as clusters of genes associated with HPV status.
View Article and Find Full Text PDFCancer Manag Res
December 2024
Department of Pulmonary Medicine, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830001, People's Republic of China.
Purpose: Lung cancer is a severe malignant tumor. This study aims to more comprehensively characterize lung cancer patients and identify combination markers for immunotherapy.
Patients And Methods: We gathered data from 166 lung cancer patients at the Cancer Hospital Affiliated with Xinjiang Medical University.
Cancer Genet
November 2024
Department of Experimental Haematooncology, Medical University of Lublin, Lublin, Poland.
The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes.
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