Identification and verification of eight cancer-associated fibroblasts related genes as a prognostic signature for head and neck squamous cell carcinoma

Liu, Dong; Sun, Qi; Song, Fei; Song, Xiaoyu; Lu, Congxian; Li, Yumei; Song, Xicheng

doi:10.1016/j.heliyon.2023.e14003

Cited by 7 publications

(3 citation statements)

References 76 publications

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“…Dong et al reported that cancer-associated fibroblasts (CAFs) within HNSC could suppress immune responses within the TME. Notably, CAFs exhibited a negative correlation with immune cell infiltration levels, prognosis, and treatment outcomes [ 36 ]. Our study extends this analysis by exploring the impact of EIF3D expression levels on the TME, immune cell infiltration, and immune checkpoint genes, shedding light on the potential role of EIF3D in these intricate processes.…”

Section: Discussionmentioning

confidence: 99%

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma

Lu,

Mihoayi,

Ablikim

et al. 2024

Aging

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Study finds that eukaryotic translation initiation factor 3 subunit D (EIF3D) may play an important role in aberrant alternative splicing (AS) events in tumors. AS possesses a pivotal role in both tumour progression and the constitution of the tumour microenvironment (TME). Regrettably, our current understanding of AS remains circumscribed especially in the context of immunogene-related alternative splicing (IGAS) profiles within Head and Neck Squamous Cell Carcinoma (HNSC). In this study, we comprehensively analyzed the function and mechanism of action of EIF3D by bioinformatics analysis combined with in vitro cellular experiments, and found that high expression of EIF3D in HNSC was associated with poor prognosis of overall survival (OS) and progression-free survival (PFS). The EIF3D low expression group had a higher degree of immune infiltration and better efficacy against PD1 and CTLA4 immunotherapy compared to the EIF3D high expression group. TCGA SpliceSeq analysis illustrated that EIF3D influenced differentially spliced alternative splicing (DSAS) events involving 105 differentially expressed immunogenes (DEIGs). We observed an induction of apoptosis and a suppression of cell proliferation, migration, and invasion in EIF3D knock-down FaDu cells. RNA-seq analysis unveiled that 531 genes exhibited differential expression following EIF3D knockdown in FaDu cells. These include 52 DEIGs. Furthermore, EIF3D knockdown influenced the patterns of 1923 alternative splicing events (ASEs), encompassing 129 IGASs. This study identified an RNA splicing regulator and revealed its regulatory role in IGAS and the TME of HNSC, suggesting that EIF3D may be a potential target for predicting HNSC prognosis and immunotherapeutic response.

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Section: Discussionmentioning

confidence: 99%

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma

Lu,

Mihoayi,

Ablikim

et al. 2024

Aging

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“…The concept of α-SMA upregulation as a sign for activated CAFs is currently questioned due to existence of α-SMA low CAFs ( Patel et al, 2018 ). With the rise of high-resolution sequencing techniques, including single cell RNA sequencing, multiple gene signatures and biomarkers for CAFs have been identified primarily at the RNA level ( Yamamoto et al, 2022 ; Zhou et al, 2022 ; Dong et al, 2023 ; Dwivedi et al, 2023 ). CAFs are presumed to be of various cell origins with diverse protumorigenic and arguably also tumor suppressive functions ( Kalluri, 2016 ; Wang et al, 2022 ; Grout et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma

Lyu,

Johannsen,

Simon

et al. 2024

Front. Cell Dev. Biol.

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Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration.Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed.Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006).Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

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“…The CD4 memory resting T cells affected T cell receptor signaling and CD4 + T cell activation by N-glycans and were associated with cell adhesion, tumor immunity, and metastasis [ 25 ]. Follicular helper T cell infiltration was shown to promote immune activation of TME and promote tumor killing, indicating a good prognosis in HNSCC [ 26 ]. Similarly, as immune-activated cells, gamma delta T cell enrichment was observed in TME, with a high expression of immune-positive regulatory chemokines in non-small cell lung cancer [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

A novel immune-related prognostic model with surgical status to predict tumor immune cell infiltration and drug sensitivity in head and neck squamous cell carcinoma

Identification and verification of eight cancer-associated fibroblasts related genes as a prognostic signature for head and neck squamous cell carcinoma

Cited by 7 publications

References 76 publications

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma

RNA splicing regulator EIF3D regulates the tumor microenvironment through immunogene-related alternative splicing in head and neck squamous cell carcinoma

Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma

A novel immune-related prognostic model with surgical status to predict tumor immune cell infiltration and drug sensitivity in head and neck squamous cell carcinoma

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