RESUMO
Lung cancer is one of the most frequently diagnosed malignancies and is a widespread disease that affects millions of individuals globally. CXCL17 is a member of the CXC chemokine family that attracts myeloid cells and is associated with the mucosa. CXCL17 can both support and suppress tumor growth in certain types of cancer. A549 LUAD cells were transfected with N-Terminal p3XFLAG-CMV or N-Terminal p3XFLAG-CMV-CXCL17 to establish stably transfected CXCL17-overexpressing cells. Reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme Linked Immunosorbent Assay (ELISA) were performed to verify the levels of CXCL17 mRNA and of CXCL17 protein concentration of stably transfected A549 cells respectively. Wound healing, CCK8, and matrigel invasion assays were performed to assess the effect of CXCL17 overexpression on migration, proliferation, and invasion of A549 cells. When compared to control groups, proliferative capacity of A549 cells were unaffected by CXCL17 overexpression; however, the wound area in the CXCL17 overexpression group had dramatically decreased after 48 h. Similarly, the number of invasion cells was significantly higher in the CXCL17-overexpressing group than in the control ones after 48 h. CXCL17 overexpression significantly increased the ability of A549 cells to migrate and invade, without affecting their proliferative abilities.
RESUMO
Background: 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. Methods: 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. Results: We found that TP53, PTEN, PIK3CA, IL7R, and KMT2D genes were commonly mutated genes in all three types of cancer via 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. Conclusion: In conclusion, a total of 96 mutated genes in LMC were investigated via meta-analysis. Our findings suggested vital roles of TP53, PTEN, PIK3CA, KMT2D, and IL7R, 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.
