Combinatorial Pan-cancer analysis of NF1 in Multiple Cancers

The GTPase-activating protein, NF1, negatively regulates the RAS/MAPK signaling pathway. Higher mutation rates of NF1 negatively impact cancer cell signaling and progression by altering cellular pathways. The expression pattern of the NF1 gene in both normal and cancer cells of different types as well as their mutations and gene networks need to be evaluated for better cancer management and enhancing therapeutic drug development pipelines. Herein, the expression pattern of the NF1 gene was explored via the GEPIA2, GENT2, and UALCAN tools. Lower expression and methylation rates were found in most cancer types, but variability was observed based on race, gender, and cancer stage. The corresponding protein levels in normal and cancer tissues were also investigated, revealing medium staining and moderate intensity in normal lung tissues but high staining and strong intensity in lung cancer tissues as well as in other cancer types. Additionally, 15 missense mutations, 351 truncations, no inframe mutations, 97 splices and 48 fusions were found in the NF1 gene through cBioportal, where amplifications, deep deletions, structural variants, and multiple alterations were observed. The SUZ12 gene was found among the most correlated and co-expressed genes of NF1 in BRCA, KIRC, LIHC, and LUAD. This study suggests the variable role of NF1 in normal tissues and cancer tissues in terms of cancer progression, gene expression, and methylation level and should be extended for therapeutics development against cancer.