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. 2023 Aug 31;14:1181775. doi: 10.3389/fgene.2023.1181775

FIGURE 1.

FIGURE 1

Schematic representation of the study design and data analysis. (A) Study population comprising GEO cohorts from three cancers associated with high nerve density and PNI, HNSCC (four datasets), PDAC (four datasets), and STAD (five datasets) (Table 1). The total number of tumor (T) versus control (C) samples are indicated. The fold change in gene expression between tumor and control tissue was performed through the software GEO2R. Genes with |log2FC|>1 and adj. p-val <0.05 were considered differentially expressed genes (DEGs). The number of DEGs for each cancer is indicated. For each cancer type, DEGs common in at least three datasets from the same cancer type were identified (pink). An intersection between the DEGs common in at least three datasets for each cancer were subsequently cross-referenced between PDAC, HNSCC, and STAD to identify common genes and gene ontology performed (pink). (B) The DEGs identified in (A) were cross-referenced with a neurodevelopmental gene signature (QuickGO GO:0007399) (green). A total of 372 neurodevelopmental DEGs were isolated in HNSCC, 419 in PDAC, and 680 in STAD. Neurodevelopmental DEGs were intersected among all cancers analyzed (green). (C) DEGs from each cancer type were analyzed for the presence of axon guidance genes. This resulted in 52 individual axon guidance genes across cancers comprising 17 common axon guidance gene families dysregulated in all cancers. (D) These results were further analyzed using TCGA data cohorts including the same cancers to the GEO analysis in addition to other cancer types associated with high nerve density and PNI: BRCA, PRCA, CHOL, and COAD. This analysis included gene expression comparison between tumor and control tissue and survival analysis. Abbreviations: GEO, Gene Expression Omnibus database; HNSCC, head and neck squamous cell carcinoma; PDAC, pancreatic ductal adenocarcinoma; STAD, stomach adenocarcinoma; DEG, differentially expressed gene; FC, fold change; TCGA, The Cancer Genome Atlas; BRCA, breast cancer; PRCA, prostate cancer; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma.