Mesh : Humans Focal Adhesions Focal Adhesion Kinase 1 / genetics metabolism Neoplasms / genetics therapy Prognosis Immunotherapy Tumor Microenvironment

来  源:   DOI:10.1097/MD.0000000000037362   PDF(Pubmed)

Abstract:
The immune environment in tumors is the key factor affecting the survival and immunotherapeutic response of patients. This research aimed to explore the underlying association between focal adhesion tyrosine kinase (FAK/PTK2) and cancer immunotherapy in 33 human cancers. Gene expression data and clinical features of 33 cancers were retrieved from the Cancer Genome Atlas Database. The immunotherapy cohorts included GSE67501, GSE78220, and IMVIGOR210, which were derived from the comprehensive gene expression database or from previous studies. Clinical parameters including patient age, gender, survival rate, and tumor stage were analyzed to evaluate the prognostic value of FAK/PTK2. FAK/PTK2 activity was detected by single-sample gene set enrichment analysis and used to compare the difference between FAK/PTK2 transcriptome and protein expression levels. To better understand the role of FAK/PTK2 in cancer immunotherapy, we analyzed its correlations with tumor microenvironment and with immune processes/elements (e.g., immune cell infiltration, immunosuppressants, and stimulants) and major histocompatible complexes. Potential pathways associated with FAK/PTK2 signaling in cancers were also explored. Correlations between FAK/PTK2 and 2 immunotherapeutic biomarkers (tumor mutation load and microsatellite instability) were studied. Finally, the 3 independent immunotherapy cohorts were used to study the relationship between FAK/PTK2 and immunotherapeutic response. Although FAK/PTK2 is not closely associated with age (13/33), gender (5/33), or tumor stage (5/33) in any of the studied human cancers, it has potential prognostic value for predicting patient survival. Consistency between FAK/PTK2 activity and expression exists in some cancers (3/33). Generally, FAK/PTK2 is robustly correlated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Moreover, high FAK/PTK2 expression is significantly related to immune-relevant pathways. However, FAK/PTK2 is not significantly correlated with the immunotherapeutic response. Research on the immunotherapeutic value of FAK/PTK2 in 33 human cancers provides evidence regarding the function of FAK/PTK2 and its role in clinical treatment. However, given the use of a bioinformatics approach, our results are preliminary and require further validation.
摘要:
肿瘤中的免疫环境是影响患者生存和免疫治疗反应的关键因素。本研究旨在探讨粘着斑酪氨酸激酶(FAK/PTK2)与33种人类癌症的癌症免疫治疗之间的潜在关联。从癌症基因组图谱数据库检索33种癌症的基因表达数据和临床特征。免疫疗法队列包括GSE67501,GSE78220和IMVIGOR210,它们来自综合基因表达数据库或以前的研究。临床参数包括患者年龄,性别,存活率,分析FAK/PTK2的预后价值。通过单样品基因集富集分析检测FAK/PTK2活性,并用于比较FAK/PTK2转录组和蛋白质表达水平之间的差异。为了更好地了解FAK/PTK2在癌症免疫治疗中的作用,我们分析了其与肿瘤微环境和免疫过程/元素的相关性(例如,免疫细胞浸润,免疫抑制剂,和兴奋剂)和主要的组织相容性复合物。还探索了与癌症中的FAK/PTK2信号传导相关的潜在途径。研究了FAK/PTK2与2种免疫治疗生物标志物(肿瘤突变负荷和微卫星不稳定性)之间的相关性。最后,3个独立的免疫治疗队列用于研究FAK/PTK2与免疫治疗应答之间的关系.尽管FAK/PTK2与年龄并不密切相关(13/33),性别(5/33),或任何研究的人类癌症的肿瘤分期(5/33),它对预测患者生存具有潜在的预后价值.FAK/PTK2活性和表达之间的一致性存在于一些癌症中(3/33)。一般来说,FAK/PTK2与免疫细胞浸润密切相关,免疫调节剂,和免疫治疗标志物。此外,FAK/PTK2高表达与免疫相关途径显著相关。然而,FAK/PTK2与免疫治疗反应无显著相关性。对FAK/PTK2在33种人类癌症中的免疫治疗价值的研究为FAK/PTK2的功能及其在临床治疗中的作用提供了证据。然而,考虑到生物信息学方法的使用,我们的结果是初步的,需要进一步验证.
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