Integrated analysis of the clinical consequence and associated gene expression of ALK in ALK-positive human cancers.
Integrated analysis of the clinical consequence and associated gene expression of ALK in ALK-positive human cancers.
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ALK阳性人类癌症中ALK的临床后果和相关基因表达的综合分析。
DOI：
10.1016/j.heliyon.2022.e09878
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发表时间：
2022-07
期刊：
影响因子：
4
通讯作者：
Tsukahara, Toshifumi
中科院分区：
文献类型：
--
作者：
Saifullah;Tsukahara, Toshifumi
间变性淋巴瘤激酶（ALK）是一种酪氨酸激酶受体，在多种癌症（包括NSCLC、黑色素瘤、淋巴瘤和其他肿瘤）中发生遗传改变。尽管ALK与多种癌症相关，但ALK表达与不同癌症患者预后之间的关系尚不清楚。在这里，我们使用多维方法，揭示了ALK表达与LUAD、黑色素瘤、OV、DLBC、AML和BC患者临床结局之间的相关性。我们分析了ALK转录表达、患者生存率、遗传改变、蛋白质网络以及基因和microRNA（miRNA）共表达。与正常组织相比，在LUAD、黑色素瘤和OV中发现了更高的ALK表达，这与患者生存率低相关。相反，发现较低的转录表达降低DLBC、AML和BC患者的存活率。共鉴定出202个错义突变、17个截短突变、7个融合突变和3个框内突变。此外，发现17个基因和19个miRNA专门共表达，棘皮动物微管相关蛋白样4（EML 4）被鉴定为最正相关的基因（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ALK作为癌症的预后生物标志物和治疗靶点提供了基础，这可能有助于精确肿瘤学并帮助临床医生确定合适的治疗方案。ALK表达;患者预后; LUAD;共表达;癌症。
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is genetically altered in several cancers, including NSCLC, melanoma, lymphoma, and other tumors. Although ALK is associated with various cancers, the relationship between ALK expression and patient prognosis in different cancers is poorly understood. Here, using multidimensional approaches, we revealed the correlation between ALK expression and the clinical outcomes of patients with LUAD, melanoma, OV, DLBC, AML, and BC. We analyzed ALK transcriptional expression, patient survival rate, genetic alteration, protein network, and gene and microRNA (miRNA) co-expression. Compared to that in normal tissues, higher ALK 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 (EML4) was identified as the most positively correlated gene (log odds ratio >3). The gene ontology and signaling pathways of the genes co-expressed with ALK in these six cancers were also identified. Our findings offer a basis for ALK as a prognostic biomarker and therapeutic target in cancers, which will potentially contribute to precision oncology and assist clinicians in identifying suitable treatment options. ALK expression; Patient prognosis; LUAD; Co-expression; Cancers.
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影响因子：
14.9
作者：
Ghoussaini M;Mountjoy E;Carmona M;Peat G;Schmidt EM;Hercules A;Fumis L;Miranda A;Carvalho-Silva D;Buniello A;Burdett T;Hayhurst J;Baker J;Ferrer J;Gonzalez-Uriarte A;Jupp S;Karim MA;Koscielny G;Machlitt-Northen S;Malangone C;Pendlington ZM;Roncaglia P;Suveges D;Wright D;Vrousgou O;Papa E;Parkinson H;MacArthur JAL;Todd JA;Barrett JC;Schwartzentruber J;Hulcoop DG;Ochoa D;McDonagh EM;Dunham I
通讯作者：
Dunham I
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
--
作者：
Hanna MG;Najfeld V;Irie HY;Tripodi J;Nayak A
通讯作者：
Nayak A
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
针对JAK/STAT3信号传导的靶向封锁抑制了卵巢癌的生长。
影响因子：
5.7
作者：
Gritsina G;Xiao F;O'Brien SW;Gabbasov R;Maglaty MA;Xu RH;Thapa RJ;Zhou Y;Nicolas E;Litwin S;Balachandran S;Sigal LJ;Huszar D;Connolly DC
通讯作者：
Connolly DC