PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer

Abstract Background Immunotherapies that targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have obtained prominent success in breast cancer (BC). However, not all the patients benefit from the antibody therapy. This study aimed to identify PD-1/PD-L1 correlated genes and pathways as well as investigate their potential as prognostic marker in BC. Materials and methods By analysing transcriptional data of BC from TCGA, we identified PD-1 and PD-L1 correlated genes by WGCNA analysis and explored the biological process as well as pathways they enriched. Co-expression analysis were performed for PD-1/PD-L1 with immune infiltration and checkpoints. The prognostic value of PD-1 and PD-L1 were also investigated. Results PD-1 and PD-L1 expression showed significant difference in different molecular subtypes and stages. PD-1 correlated genes enriched in T cell activation, lymphocyte activation, leukocyte migration while PD-L1 correlated genes demonstrated enrichment including T cell apoptotic process, tolerance induction and cytolysis. Immune infiltration analysis suggested that PD-1 and PD-L1 were related with Neutrophils (r = 0.65, r = 0.48) and Fibroblasts (r = 0.59, r = 0.47). For immune checkpoints analysis, PD-1 was associated with HLA-A (r = 0.804) and INPP5D (r = 0.782) while PD-L1 correlated with CTLA4 (r = 0.843) and CD27 (r = 0.823). PD-1 was associated favorable survival of BC (HR = 0.67, P = 0.012) while PD-L1 did not demonstrate significant association with BC prognosis (HR = 0.85, P = 0.313). Conclusion PD-1 and PD-L1 correlated genes participated in biological process including T cell activation, lymphocyte activation, leukocyte migration, T cell apoptotic process, tolerance induction and cytolysis. PD-1/PD-L1 expression also demonstrated relation with immune infiltration and immune checkpoints. High PD-1 expression predicted better survival of breast cancer patients. </jats:sec

MOESM1 of PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer

Additional file 1: Table S1. Prognostic analysis of PD1/PDL1 co-expressing genes

Progerin modulates the IGF-1R/Akt signaling involved in aging

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24 −/− mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA -associated progeroid disorders. </jats:p