Genome‐wide postnatal changes in immunity following fetal inflammatory response

Costa, DC; Bonet, Núria; Solé, Amanda; Aledo-Castillo, José Manuel González de; Sabidó, Eduard; Casals, Ferrán; Rovira, Carlota; Nadal, Alfons; Marı́n, J. L.; Cobo, Teresa; Castelo, Robert

doi:10.1111/febs.15578

Cited by 1 publication

(1 citation statement)

References 101 publications

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“…In recent years, precision medicine has revolutionized the treatment of human cancers (Dupont et al, 2021 ), which emphasizes that, by integrating multidimensional biological data and clinical characteristics, highly heterogeneous cancers can be subdivided into more accurate subtypes for individualized treatment (Zhang et al, 2020 ). Indeed accumulating evidence established subgroups of tumor patients according to their molecular profiles, representing distinct phenotypes, prognoses, and therapy responses (Yan et al, 2018 ; Tan et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma

Wang

Chen

Ying

et al. 2021

Front. Cell Dev. Biol.

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Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC. Based on available data in The Cancer Genome Atlas, divergent expression profiles of ferroptosis regulators were noted in ccRCC and normal tissues, and we also found that the ferroptosis regulators correlated with the PD-L1 expression. Two independent subtypes were determined by consensus clustering analysis according to the expression level of ferroptosis regulators in ccRCC. Cluster 1 showed lower histological tumor stage and grade, more favorable prognosis, and higher PD-L1 expression compared to cluster 2. CIBERSORT analysis revealed that cluster 2 harbored higher infiltrated levels of CD8+ T cell, Tregs, and T follicular helper cell, while cluster 1 more correlated with the monocyte, M1 macrophage, and M2 macrophage. Gene set enrichment analysis indicated that the ERBB signaling and JAK_STAT signaling pathways were significantly enriched in cluster 1. We subsequently identified CARS as the potentially key immune infiltration-related ferroptosis regulator, whose high expression showed dismal prognosis and was positively correlated with PD-L1 expression in ccRCC. We also verified the upregulation of CARS in ccRCC tissues and cell lines via qRT-PCR method. Additionally, a pan-cancer analysis demonstrated that CARS closely related to the expression of immune checkpoint-related genes (especially PD-L1) and an unfavorable prognosis in diverse cancer types. In summary, our study suggested the crucial role of ferroptosis in immune infiltration of ccRCC, and CARS is a potentially novel prognostic biomarker and potential target for cancer immunotherapy.

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