Identification and characterization of CLEC11A and its derived immune signature in gastric cancer

Abstract

IntroductionC-type lectin domain family 11 member A (CLEC11A) was characterized as a growth factor that mainly regulates hematopoietic function and differentiation of bone cells. However, the involvement of CLEC11A in gastric cancer (GC) is not well understood.MethodsTranscriptomic data and clinical information pertaining to GC were obtained and analyzed from publicly available databases. The relationships between CLEC11A and prognoses, genetic alterations, tumor microenvironment (TME), and therapeutic responses in GC patients were analyzed by bioinformatics methods. A CLEC11A-derived immune signature was developed and validated, and its mutational landscapes, immunological characteristics as well as drug sensitivities were explored. A nomogram was established by combining CLEC11A-derived immune signature and clinical factors. The expression and carcinogenic effects of CLEC11A in GC were verified by qRT−PCR, cell migration, invasion, cell cycle analysis, and in vivo model analysis. Myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and T cells in tumor samples extracted from mice were analyzed utilizing flow cytometry analysis.ResultsCLEC11A was over-expressed in GC, and the elevated CLEC11A expression indicated an unfavorable prognosis in GC patients. CLEC11A was involved in genomic alterations and associated with the TME in GC. Moreover, elevated CLEC11A was found to reduce the benefit of immunotherapy according to immunophenoscore (IPS) and the tumor immune dysfunction, exclusion (TIDE). After validation, the CLEC11A-derived immune signature demonstrated a consistent ability to predict the survival outcomes in GC patients. A nomogram that quantifies survival probability was constructed to improve the accuracy of prognosis prediction in GC patients. Using shRNA to suppress the expression of CLEC11A led to significant inhibitions of cell cycle progression, migration, and invasion, as well as a marked reduction of in vivo tumor growth. Moreover, the flow cytometry assay showed that the knock-down of CLEC11A increased the infiltration of cytotoxic CD8+ T cells and helper CD4+ T into tumors while decreasing the percentage of M2 macrophages, MDSCs, and Tregs.ConclusionCollectively, our findings revealed that CLEC11A could be a prognostic and immunological biomarker in GC, and CLEC11A-derived immune signature might serve as a new option for clinicians to predict outcomes and formulate personalized treatment plans for GC patients.

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update

“…In GC, CLEC11A may be a predictive and immunological biomarker. An immune signature derived from CLEC11A may offer clinicians a novel way to predict patient outcomes and create individualized treatment regimens [ 44 ]. The indicators of CD8+ T cells, neutrophils, macrophages, and dendritic cells were favorably connected with inhibitor subunit beta A (INHBA) expression, which suggests that INHBA could be a useful biomarker in the prediction of prognosis in GC patients.…”

“…the BMRG signature has proven accurate and reliable in the prediction of prognosis in GC patients [43] -CLEC11A may be a predictive and immunological biomarker [44] the INHBA is a potentially useful indicator of immunotherapy response [45] the CRG signature could be a reliable and effective tool for prognostic prediction and therapeutic guidance [46] -NK cell marker genes point to possible treatment targets [47] -CSK may predict immunotherapy and molecular targeting in addition to offering suggestions for a treatment plan [48] -ACVR1 could be a promising target for GC immunotherapy [49] Table 3. Cont.…”