دورية أكاديمية
أعرض في EDS

Comprehensive pan-cancer analysis of 33 human cancers reveals immunotherapeutic value of focal adhesion tyrosine kinase.

التفاصيل البيبلوغرافية
العنوان: Comprehensive pan-cancer analysis of 33 human cancers reveals immunotherapeutic value of focal adhesion tyrosine kinase.
المؤلفون: Shi Y; Department of Oncology, The People's Hospital of Jurong City, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, China., Ju M; Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan., Zhang Y; Department of Radiation Center, Shanghai First Maternity and Infant Hospital. School of Medicine, Tongji University, Shanghai, China., Liang L; Department of Oncology, The People's Hospital of Jurong City, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, China., Sun X; Department of Radiotherapy, Jiangsu Provincial People's Hospital, Nanjing, China., Di X; Department of Radiotherapy, Jiangsu Provincial People's Hospital, Nanjing, China.
المصدر: Medicine [Medicine (Baltimore)] 2024 Mar 22; Vol. 103 (12), pp. e37362.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 2985248R Publication Model: Print Cited Medium: Internet ISSN: 1536-5964 (Electronic) Linking ISSN: 00257974 NLM ISO Abbreviation: Medicine (Baltimore) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Hagerstown, Md : Lippincott Williams & Wilkins
مواضيع طبية MeSH: Focal Adhesions* , Neoplasms*/genetics , Neoplasms*/therapy, Humans ; Focal Adhesion Kinase 1/genetics ; Focal Adhesion Kinase 1/metabolism ; Prognosis ; Immunotherapy ; Tumor Microenvironment
مستخلص: 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.
Competing Interests: The authors have no conflicts of interest to disclose.
(Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
References: Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2:1217–22.
Keenan TE, Burke KP, Van Allen EM. Genomic correlates of response to immune checkpoint blockade. Nat Med. 2019;25:389–402.
Miao D, Margolis CA, Vokes NI, et al. Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018;50:1271–81.
Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110:673–87.
Guan JL. Integrin signaling through FAK in the regulation of mammary stem cells and breast cancer. IUBMB Life. 2010;62:268–76.
Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci. 2003;116:1409–16.
Ward KK, Tancioni I, Lawson C, et al. Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression. Clin Exp Metastasis. 2013;30:579–94.
Hanks SK, Calalb MB, Harper MC, et al. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992;89:8487–91.
Schaller MD, Borgman CA, Cobb BS, et al. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992;89:5192–6.
Weiner TM, Liu ET, Craven RJ, et al. Expression of focal adhesion kinase gene and invasive cancer. Lancet. 1993;342:1024–5.
Lark AL, Livasy CA, Calvo B, et al. Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clin Cancer Res. 2003;9:215–22.
Judson PL, He X, Cance WG, et al. Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma. Cancer. 1999;86:1551–6.
Miyazaki T, Kato H, Nakajima M, et al. FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer. 2003;89:140–5.
Itoh S, Maeda T, Shimada M, et al. Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma. Clin Cancer Res. 2004;10:2812–7.
Sood AK, Armaiz-Pena GN, Halder J, et al. Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis. J Clin Invest. 2010;120:1515–23.
Golubovskaya VM. Targeting FAK in human cancer: from finding to first clinical trials. Front Biosci (Landmark Ed). 2014;19:687–706.
Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nat Rev Cancer. 2014;14:598–610.
Popow J, Arnhof H, Bader G, et al. Highly selective PTK2 proteolysis targeting chimeras to probe focal adhesion kinase scaffolding functions. J Med Chem. 2019;62:2508–20.
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21:309–22.
Zheng X, Hu Y, Yao C. The paradoxical role of tumor-infiltrating immune cells in lung cancer. Intractable Rare Dis Res. 2017;6:234–41.
Serrels A, Lund T, Serrels B, et al. Nuclear FAK controls chemokine transcription, Tregs, and evasion of antitumor immunity. Cell. 2015;163:160–73.
Kasorn A, Alcaide P, Jia Y, et al. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and-independent cellular signals. J Immunol. 2009;183:1032–43.
Mitra SK, Lim ST, Chi A, et al. Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene. 2006;25:4429–40.
Stokes JB, Adair SJ, Slack-Davis JK, et al. Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011;10:2135–45.
Batista S, Maniati E, Reynolds LE, et al. Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis. Nat Commun. 2014;5:5054.
Abshire MY, Thomas KS, Owen KA, et al. Macrophage motility requires distinct alpha5beta1/FAK and alpha4beta1/paxillin signaling events. J Leukoc Biol. 2011;89:251–7.
Tomczak K, Czerwińska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Pozn). 2015;19:A68–77.
Mariathasan S, Turley SJ, Nickles D, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.
Neavin DR, Lee JH, Liu D, et al. Single nucleotide polymorphisms at a distance from aryl hydrocarbon receptor (AHR) binding sites influence AHR ligand-dependent gene expression. Drug Metab Dispos. 2019;47:983–94.
Yoshihara K, Shahmoradgoli M, Martínez E, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.
Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.
Bonneville R, Krook MA, Kautto EA, et al. Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017;2017:PO.17.00073.
Canel M, Secades P, Rodrigo JP, et al. Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number. Clin Cancer Res. 2006;12(11 Pt 1):3272–9.
Okamoto H, Yasui K, Zhao C, et al. PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas. Hepatology. 2003;38:1242–9.
Rodrigo JP, Álvarez-Alija G, Menéndez ST, et al. Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy. Cancer Prev Res (Phila). 2011;4:1333–41.
Ilic D, Kovacic B, McDonagh S, et al. Focal adhesion kinase is required for blood vessel morphogenesis. Circ Res. 2003;92:300–7.
Lim ST, Chen XL, Tomar A, et al. Knock-in mutation reveals an essential role for focal adhesion kinase activity in blood vessel morphogenesis and cell motilitypolarity but not cell proliferation. J Biol Chem. 2010;285:21526–36.
Lim ST, Miller NL, Chen XL, et al. Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression. J Cell Biol. 2012;197:907–19.
Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016;22:851–60.
Serrels B, McGivern N, Canel M, et al. IL-33 and ST2 mediate FAK-dependent antitumor immune evasion through transcriptional networks. Sci Signaling. 2017;10:eaan8355.
Dunn KB, Heffler M, Golubovskaya VM. Evolving therapies and FAK inhibitors for the treatment of cancer. Anticancer Agents Med Chem. 2010;10:722–34.
Tai YL, Chen LC, Shen TL. Emerging roles of focal adhesion kinase in cancer. Biomed Res Int. 2015;2015:690.
Golubovskaya VM, Zheng M, Zhang L, et al. The direct effect of focal adhesion kinase (FAK), dominant-negative FAK, FAKCD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis. BMC Cancer. 2009;9:280.
Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41:49–61.
Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306.
Atreya I, Neurath MF. Immune cells in colorectal cancer: prognostic relevance and therapeutic strategies. Expert Rev Anticancer Ther. 2008;8:561–72.
Zuo S, Wei M, Wang S, et al. Pan-cancer analysis of immune cell infiltration identifies a prognostic immune-cell characteristic score (ICCS) in lung adenocarcinoma. Front Immunol. 2020;11:1218.
Chan TA, Yarchoan M, Jaffee E, et al. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019;30:44–56.
Yamamoto H, Imai K. An updated review of microsatellite instability in the era of next-generation sequencing and precision medicine. Semin Oncol. 2019;46:261–70.
المشرفين على المادة: EC 2.7.10.2 (Focal Adhesion Kinase 1)
تواريخ الأحداث: Date Created: 20240322 Date Completed: 20240325 Latest Revision: 20240329
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC10956984
DOI: 10.1097/MD.0000000000037362
PMID: 38518034
قاعدة البيانات: MEDLINE
الوصف
تدمد:1536-5964
DOI:10.1097/MD.0000000000037362