Meta-analysis of commonly mutated genes in leptomeningeal carcinomatosis

• Published in: PeerJ (San Francisco, CA) Vol. 11; p. e15250
• Main Authors: Congur, Irem, Koni, Ekin, Onat, Onur Emre, Tokcaer Keskin, Zeynep
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 19-04-2023; PeerJ Inc
• Subjects: Analysis; Bioinformatic analysis; Bioinformatics; Breast Neoplasms - complications; Carcinoma, Non-Small-Cell Lung - complications; Cell Biology; Female; Gene mutations; Genes; Humans; Leptomeningeal carcinomatosis; Lung cancer, Non-small cell; Lung Neoplasms - complications; Medical research; Medicine, Experimental; Melanoma; Melanoma - complications; Meningeal Carcinomatosis - complications; Metastasis; Molecular Biology; Oncology; Pathology; Pathway enrichment analysis; Protein-protein interaction; Protein-protein interactions; Tumor proteins; United States; United States; Pathway enrichment analysis; Bioinformatic analysis; Protein-protein interaction; Leptomeningeal carcinomatosis
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.15250

Leptomeningeal carcinomatosis (LMC) is a rare type of cancer that settles at the meninges through metastasis of non-small cell lung cancer (NSCLC), breast cancer and melanoma. The molecular mechanism underlying LMC is not known, therefore molecular studies investigating the development of LMC are needed. Here, we aimed to identify commonly mutated genes in LMC caused by NSCLC, breast cancer, and melanoma using an in-slico approach and their interactions using integrated bioinformatic approaches/tools in this meta-analysis.
We conducted a meta-analysis using information from 16 studies that included different sequencing techniques of patients with LMC caused by three different primary cancers: breast cancer, NSCLC, and melanoma. All studies that assessed mutation information from patients with LMC were searched in PubMed, from their inception to February, 16 2022. Studies that performed NGS on LMC patients with NSCLC, breast cancer, or melanoma were included, while studies that did not apply NGS to CSF samples, did not provide information on altered genes, were reviews, editorials, or conference abstracts, or whose main goal was the detection of malignancies were all excluded. We identified commonly mutated genes in all three types of cancer. Next, we constructed a protein-protein interaction network, then performed pathway enrichment analysis. We searched National Institutes of Health (NIH) and Drug-Gene Interaction Database (DGIdb) to find candidate drugs.
We found that
, and
genes were commonly mutated genes in all three types of cancer
our meta-analysis that consisted out of 16 studies. Our pathway enrichment analysis showed that all five genes were primarily associated with regulation of cell communication and signaling, and cell proliferation. Other enriched pathways included regulation of apoptotic processes of leukocytes and fibroblasts, macroautophagy and growth. According to our drug search we found candidate drugs; Everolimus, Bevacizumab and Temozolomide, which interact with these five genes.
In conclusion, a total of 96 mutated genes in LMC were investigated
meta-analysis. Our findings suggested vital roles of
, and
, which can provide insight into the molecular basis of LMC development and paving the door to the development of new targeted medicine and will encourage molecular biologists to seek biological evidence.