Tsukahara Toshifumi
Area of Bioscience and Biotechnology, School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi City, Ishikawa, 923-1292, Japan.
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira City, Tokyo, 187-8502, Japan.
Heliyon. 2022 Jul 9;8(7):e09878. doi: 10.1016/j.heliyon.2022.e09878. eCollection 2022 Jul.
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is genetically altered in several cancers, including NSCLC, melanoma, lymphoma, and other tumors. Although is associated with various cancers, the relationship between expression and patient prognosis in different cancers is poorly understood. Here, using multidimensional approaches, we revealed the correlation between expression and the clinical outcomes of patients with LUAD, melanoma, OV, DLBC, AML, and BC. We analyzed transcriptional expression, patient survival rate, genetic alteration, protein network, and gene and microRNA (miRNA) co-expression. Compared to that in normal tissues, higher expression was found in LUAD, melanoma, and OV, which are associated with poor patient survival rates. In contrast, lower transcriptional expression was found to decrease the survival rate of patients with DLBC, AML, and BC. A total of 202 missense mutations, 17 truncating mutations, 7 fusions, and 3 in-frame mutations were identified. Further, 17 genes and 19 miRNAs were found to be exclusively co-expressed and echinoderm microtubule-associated protein-like 4 () was identified as the most positively correlated gene (log odds ratio >3). The gene ontology and signaling pathways of the genes co-expressed with in these six cancers were also identified. Our findings offer a basis for as a prognostic biomarker and therapeutic target in cancers, which will potentially contribute to precision oncology and assist clinicians in identifying suitable treatment options.
间变性淋巴瘤激酶(ALK)是一种酪氨酸激酶受体,在包括非小细胞肺癌(NSCLC)、黑色素瘤、淋巴瘤和其他肿瘤在内的多种癌症中发生基因改变。尽管ALK与多种癌症相关,但在不同癌症中其表达与患者预后之间的关系却知之甚少。在此,我们采用多维方法揭示了ALK表达与肺腺癌(LUAD)、黑色素瘤、卵巢癌(OV)、弥漫性大B细胞淋巴瘤(DLBC)、急性髓系白血病(AML)和乳腺癌(BC)患者临床结局之间的相关性。我们分析了ALK的转录表达、患者生存率、基因改变、蛋白质网络以及基因与微小RNA(miRNA)的共表达情况。与正常组织相比,在LUAD、黑色素瘤和OV中发现ALK表达较高,这与患者较差的生存率相关。相反,发现DLBC、AML和BC患者中较低的转录表达会降低生存率。共鉴定出202个错义突变、17个截短突变、7个融合以及3个框内突变。此外,发现17个基因和19个miRNA仅共表达,并且棘皮动物微管相关蛋白样4(EML4)被确定为相关性最强的基因(对数优势比>3)。还确定了这六种癌症中与ALK共表达的基因的基因本体和信号通路。我们的研究结果为将ALK作为癌症的预后生物标志物和治疗靶点提供了依据,这可能有助于精准肿瘤学,并协助临床医生确定合适的治疗方案。