Background: The FAT atypical cadherin 1/2/3/4 (FAT1/2/3/4) has been linked to the occurrence and development of various cancers. However, the prognostic and immunological role of FAT1/2/3/4 in non-small cell lung cancer (NSCLC) has not been clarified.
Methods: The association of FAT1/2/3/4 mutations with tumor mutation burden (TMB), tumor immunity in the microenvironment, and response to ICIs in NSCLC was investigated. Whole-exome sequencing data of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) samples from the Cancer Genome Atlas (TCGA), and an immunotherapy data set comprising mutation and survival data of 75 NSCLC patients were analyzed. Two independent pan-cancer cohorts with large samples were used to validate the prognostic value of FAT1/2/3/4 mutations in immunotherapy.
Results: A high mutation rate of FAT1/2/3/4 (57.3%, 603/1052) was observed in NSCLC patients. TMB was significantly higher in samples with mutated FAT1/2/3/4 compared to samples with wildtype FAT1/2/3/4 ( < .05). FAT2 mutation was found to be an independent prognostic biomarker in LUAD. FAT1/2/3/4 were aberrantly expressed in LUAD and LUSC, and high FAT2 expression strongly correlated with high PD-L1 levels in LUAD. Moreover, LUAD patients with FAT1 mutations showed significantly high activated dendritic cells infiltration, whereas those with FAT2/3/4 mutations had high infiltration of CD8 T-cells, M1 macrophages, activated memory CD4 T-cells, and helper follicular T-cells. It was also observed that FAT1/2/4 mutations were significantly associated with better enhanced objective response and durable clinical benefit, whereas FAT1/2/3 mutations correlated with longer progression-free survival in ICI-treated NSCLC cohort. FAT1/4 mutations were related to better overall survival in pan-cancer patients treated with ICIs.
Conclusions: FAT family genes are potential prognostic and immunological biomarkers and correlate with response to ICIs in NSCLC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891876 | PMC |
| http://dx.doi.org/10.1177/10732748221076682 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection.
J Trauma Acute Care Surg
January 2025
From the Division of Trauma and Critical Care, Department of Surgery (K.S.A.), Feinberg School of Medicine, Northwestern University, Illinois; Department of Surgery (K.S.A.), School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin; Department of Organ Surgery and Transplantation (M.A.C.) and Department of Organ Surgery and Transplantation (A.B.), University of Copenhagen, Copenhagen, Denmark; Department of Surgery (W.-Q.W.), Vanderbilt University Medical Center, Tennessee, Nashville; Department of Surgery (A.K.), Columbia University Medical Center, New York; Center for Genetic Medicine (J.P., M.R.-P.), Feinberg School of Medicine, Northwestern University; Department of Anesthesiology (R.J.M.), Rush University Medical Center; Division of Trauma and Critical Care, Department of Surgery (H.B.A.), Feinberg School of Medicine, Northwestern University, Chicago, IL; and Department of Organ Surgery and Transplantation (M.H.S.), University of Copenhagen, Copenhagen, Denmark.
Background: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs).
View Article and Find Full Text PDFMultiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC.
Sci Rep
January 2025
Jiangxi Key Laboratory of Molecular Medicine, Jiangxi Medical College, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, 330006, China.
SMAD3, a protein-coding gene, assumes a pivotal role within the transforming growth factor-beta (TGF-β) signaling pathway. Notably, aberrant SMAD3 expression has been linked to various malignancies. Nevertheless, an extensive examination of the comprehensive pan-cancer impact on SMAD3's diagnostic, prognostic, and immunological predictive utility has yet to be undertaken.
View Article and Find Full Text PDFTertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma: anatomical site matters.
Cancer Immunol Immunother
January 2025
Division of Oncology, Department of Clinical Sciences Lund, and Lund University Cancer Center, Lund University, Lund, Sweden.
Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC.
View Article and Find Full Text PDFPrognostic Factors Predicting Remission Following Rituximab Therapy for Pemphigus Vulgaris.
Acta Derm Venereol
January 2025
Department of Dermatology, Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel.
Pemphigus vulgaris is a chronic autoimmune blistering disease with significant morbidity. Rituximab, approved as its first-line treatment, effectively induces remission. However, few studies have analysed the prognostic factors for improved rituximab outcomes.
View Article and Find Full Text PDFMachine-learning derived identification of prognostic signature to forecast head and neck squamous cell carcinoma prognosis and drug response.
Front Immunol
January 2025
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Introduction: Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous malignancy is often associated with unfavorable prognosis. Due to its unique anatomical position and the absence of effective early inspection methods, surgical intervention alone is frequently inadequate for achieving complete remission. Therefore, the identification of reliable biomarker is crucial to enhance the accuracy of screening and treatment strategies for HNSCC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!