Abstract
Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in children. The aggressive behavior of ACP challenges the treatment for it. However, immunotherapy is rarely studied in ACP. In this research, we performed unsupervised cluster analysis on the 725 immune-related genes and arrays of 39 patients with ACP patients in GSE60815 and GSE94349 databases. Two novel immune subtypes were identified, namely immune resistance (IR) subtype and immunogenic (IG) subtype. Interestingly, we found that the ACPs with IG subtype (34.78%, 8/23) were more likely to respond to immunotherapy than the ACPs with IR subtype (6.25%, 1/16) via tumor immune dysfunction and exclusion (TIDE) method. Simultaneously, the enrichment analysis indicated that the differentially expressed genes (DEGs) (p < 0.01, FDR < 0.01) of the IG subtype were chiefly involved in inflammatory and immune responses. However, the DEGs of the IR subtype were mainly involved in RNA processing. Next, immune infiltration analysis revealed a higher proportion of M2 macrophage in the IG subtype than that in the IR subtype. Compared with the IR subtype, the expression levels of immune checkpoint molecules (PD1, PDL1, PDL2, TIM3, CTLA4, Galectin9, LAG3, and CD86) were significantly upregulated in the IG subtype. The ssGSEA results demonstrated that the biofunction of carcinogenesis in the IG subtype was significantly enriched, such as lymphocyte infiltration, mesenchymal phenotype, stemness maintenance, and tumorigenic cytokines, compared with the IR subtype. Finally, a WDR89 (the DEG between IG and IR subtype)-based nomogram model was constructed to predict the immune classification of ACPs with excellent performance. This predictive model provided a reliable classification assessment tool for clinicians and aids treatment decision-making in the clinic.
Highlights
Craniopharyngioma (CP) constitutes 1.2–4.6% of all intracranial tumors, accounting for 0.5–2.5 new cases per 1 million population per year globally, of which 30–50% are diagnosed during childhood and adolescence [1,2,3]
The tumor immune dysfunction and exclusion (TIDE) results showed that the Adamantinomatous craniopharyngioma (ACP) with cluster 2 and cluster A (50%, 4/8; 71.43%, 10/14) were more likely to respond to immunotherapy than the ACPs with cluster 1 and cluster B (0%, 0/7; 30%, 3/10) (Figures 1D–F)
Cancer immunotherapy has completely revolutionized the treatment landscape of malignant tumors, which is a new type of treatment that has emerged after surgery, chemotherapy, radiotherapy, and targeted therapy [26, 27]
Summary
Craniopharyngioma (CP) constitutes 1.2–4.6% of all intracranial tumors, accounting for 0.5–2.5 new cases per 1 million population per year globally, of which 30–50% are diagnosed during childhood and adolescence [1,2,3]. We collected a total of 401 samples, including 210 RNA-sequencing data from the GSE68015 database and 110 RNA-sequencing data from the GSE494349 database to investigate the intratumoral immune profile of ACP and explore a novel immune classification for predicting immunotherapy responsiveness. GSE68015 database (n = 210) contains ACP tumor samples, nine normal pituitary tissue samples (controls), normal brain tissue samples, and 170 other primary pediatric and adult brain tumor samples. GSE94349 database (n = 191) includes 24 ACP tumor samples, 23 normal pituitary samples, 27 normal brain tissue samples, and 117 surgical tumor samples of other primary pediatric and adult brain tumor types.
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