Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Quan, Zihan; Yang, Yang; Zheng, Hongmei; Zhan, Yuting; Luo, Jianmin; Ning, Yuping; Fan, Songqing

doi:10.7150/jca.77619

Cited by 34 publications

(10 citation statements)

References 107 publications

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“…The PI3K/Akt signaling pathway is mediated by enzyme-linked receptors ( Yang et al, 2022 ). PI3K/Akt can activate the signaling pathway with the participation of various growth factors, cytokines, and extracellular matrix and also plays an important role in cell proliferation, apoptosis, tissue inflammation, and tumor growth and invasion ( Wang Q. et al, 2022 ; Hashemi et al, 2022 ; Quan et al, 2022 ). Insulin-like growth factor-1(IGF-1) as well as vascular endothelial growth factor (VEGF) may promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts by regulating the PI3K/Akt/mTOR signaling pathway ( Karar and Maity, 2011 ; Bakker et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

et al. 2023

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Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis.

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Section: Discussionmentioning

confidence: 99%

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

et al. 2023

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“…Additionally, we recently identified the potential involvement of PI3K-induced signaling in the cross-talk between EGFR and PD-L1 pathways through TTF-1 upregulation ( 39 ). Indeed, PI3K-mediated signaling has been found to downregulate PD-L1 in NSCLC ( 42 ). Consequently, gene amplification of PIK3CA, a component of the PI3K complex, has been found to positively correlate with PIK3CA activating mutations ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

Luna,

Imasa,

Juat

et al. 2023

Transl Lung Cancer Res

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Background The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day. Methods We prospectively studied the outcomes of EGFR-mutant NSCLC in Filipino cohort, and retrospectively verified the survival trend using The Cancer Genome Atlas (TCGA) cohort. Kaplan-Meier method and generalized linear regression were used to assess survival. Expression and DNA methylation of cluster of differentiation 274 ( CD274 , gene that codes for PD-L1) were examined from TCGA tumor profiles. Pearson’s correlation was used to correlate PD-L1 expression with outcomes associated with occurrence of EGFR mutations, tyrosine kinase inhibitor (TKI) types, and programmed cell death protein 1 (PD-1) expression. Proteome network analysis was used to examine the correlation between drug resistance and PD-L1. Results PD-L1 positivity was associated with significantly longer progression-free survival (PFS; P=0.0096) but had a significantly contrasting influence in the overall survival (OS; P=0.0011). PD-L1 positivity (in both protein and RNA) was associated with longer median OS (mOS) in exon21 L858R, whereas, negativity was associated with longer mOS in exon19 deletion (exon19del). Stratification (high, low, negative) of PD-L1 expression lacked significant prognostic value (all P>0.05). PD-L1/ CD274 expression (P<0.05) and DNA methylation (P<0.001) vary significantly among NSCLC subtypes and in different disease stages. Erlotinib treatment produced the longest median progression-free survival (mPFS; 874 days) relative to other EGFR-TKIs (137–311 days). PD-L1 lacked a significant correlation with EGFR-TKIs. Consistent with the immune-regulation activities of PD-1, higher expression leads to relatively shorter mOS. PD-1 correlated positively with PD-L1 expression and occurrence of exon21 L858R. Conclusions PD-L1 differentially influenced the outcomes of Filipinos with EGFR-mutant NSCLC. NSCLC subtypes, disease stage, and PD-1 expression may impact the collective outcomes associated with PD-L1 and EGFR-sensitizing mutations.

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“…In colorectal cancer, PD-L1 was shown to enhance EMT through the RAS/MEK/ERK pathway and to interact with the 1-86 amino acid segment of KRAS and transduce signals 11 . In contrast, in non-small cell lung cancer (NSCLC), overexpressed PD-L1 enhances the migration and invasion of cancer cells by activating the PI3K/AKT pathway 12 . In addition, PD-L1 can directly bind to integrin 4 to activate the AKT/GSK3 signaling cascade and then stimulate the transcriptional repressor SNAI1, which decreases SIRT3 promoter activity, hence promoting EMT and increasing glucose uptake of tumor cells (Fig.…”

Section: Mechanism Of Pd-l1 Actionmentioning

confidence: 99%

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

Zhang¹,

Wu²,

Zhao³

et al. 2023

J. Cancer

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Programmed death-1 is a protein found on the surface of immune cells that can interact with its ligand, programmed death-ligand 1 (PD-L1), which is expressed on the plasma membrane, the surface of secreted cellular exosomes, in cell nuclei, or as a circulating soluble protein. This interaction can lead to immune escape in cancer patients. In clinical settings, PD-L1 plays an important role in tumor disease diagnosis, determining therapeutic effectiveness, and predicting patient prognosis. PD-L1 inhibitors are also essential components of tumor immunotherapy. Thus, the detection of PD-L1 levels is crucial, especially in the era of precision cancer therapy. In recent years, innovations have been made in traditional immunoassay methods and the development of new immunoassays for PD-L1 detection. This review aims to summarize recent research progress in tumor PD-L1 detection technology and highlight the clinical applications of PD-L1.

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Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Cited by 34 publications

References 107 publications

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

Recent Advancement of PD-L1 Detection Technologies and Clinical Applications in the Era of Precision Cancer Therapy

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