Glioma is the most common of brain tumors that greatly affects patient survival. In our precious study, Crk-like adapter protein (CrkL) was identified as a key regulator in glioblastoma development . Here, we aimed to investigate the correlation of CrkL with patient prognosis as well as pathological indicators. Immunohistochemistry was available to evaluate CrkL expression in 49 gliomas of distinct malignancy grade, and positive stained sites were analyzed. CrkL protein was detected in cell lines by Western blot as well. We observed CrkL protein stained in 59.2 % (29 out of 49) of all glioma tissues, including 41.4 % of low-grade (I + II) gliomas, and 85.0 % of high-grade (III + IV) gliomas. Of four grades, grade IV exhibited the highest CrkL level. CrkL protein was also identified in cell lines NHA, U87, U251, T98G, and A172 by Western blot. On the other hand, CrkL expression was significantly associated with the patient’s age and WHO grade, and patients with high CrkL expression had a significantly shorter median survival time (17 months) than those (median survival time 52 months) with low CrkL expression (p < 0.001). According to Cox regression, CrkL can be suggested as an independent prognostic factor. In conclusion, CrkL is differently expressed in different grades of gliomas, and correlated to WHO grade. CrkL also independently indicates poor prognosis in old glioma patients, which can further be recommended as an effective prognostic biomarker or therapeutic target.
CrkL Immunohistochemistry Glioma Prognosis
This is a preview of subscription content, log in to check access.
This study was supported by the National Key Basic Research Program of China (No. 2013CB932502), and the National Natural Science Foundation of China (No. 81171295). We greatly thank Ranran Shi in Sandy Lab for valuable suggestions.
Conflicts of interest
The authors state that there are no conflicts of interest to disclose.
Lv S, Qin J, Yi R, Coreman M, Shi R, Kang H, et al. Crkl efficiently mediates cell proliferation, migration, and invasion induced by TGF-β pathway in glioblastoma. J Mol Neurosci. 2013;51:1046–51.CrossRefPubMedGoogle Scholar
Butowski NA, Chang SM. Glial tumors: the current state of scientific knowledge. Clin Neurosurg. 2006;53:106–13.PubMedGoogle Scholar
Yanagi H, Wang L, Nishihara H, Kimura T, Tanino M, Yanagi T, et al. CRKL plays a pivotal role in tumorigenesis of head and neck squamous cell carcinoma through the regulation of cell adhesion. Biochem Biophys Res Commun. 2012;418:104–9.CrossRefPubMedGoogle Scholar
Zhao T, Miao Z, Wang Z, Xu Y, Wu J, Liu X, et al. Overexpression of CRKL correlates with malignant cell proliferation in breast cancer. Tumour Biol. 2013;34:2891–7.CrossRefPubMedGoogle Scholar
Wang Y, Dong QZ, Fu L, Stoecker M, Wang E, Wang EH. Overexpression of Crkl correlates with poor prognosis and cell proliferation in non-small cell lung cancer. Mol Carcinog. 2013;52:890–9.CrossRefPubMedGoogle Scholar
Cheung HW, Du J, Boehm JS, He F, Weir BA, Wang X, et al. Amplification of CRKL induces transformation and epidermal growth factor receptor inhibitor resistance in human non-small cell lung cancers. Cancer Discov. 2011;1:608–25.CrossRefPubMedPubMedCentralGoogle Scholar
Wang J, Che YL, Li G, Liu B, Shen TM, Wang H, et al. Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma. Mol Carcinog. 2011;50:506–15.CrossRefPubMedGoogle Scholar
Chiu ST, Chang KJ, Ting CH, Shen HC, Li H, Hsieh FJ. Over-expression of EphB3 enhances cell-cell contacts and suppresses tumor growth in HT-29 human colon cancer cells. Carcinogenesis. 2009;30:1475–86.CrossRefPubMedGoogle Scholar
Hernández-Boluda JC, Cervantes F. Prognostic factors in chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009;22:343–53.CrossRefPubMedGoogle Scholar
Evren S, Ma XZ, Sakac D, Branch DR. SHP-1 protein tyrosine phosphatase associates with the adaptor protein CrkL. Exp Hematol. 2012;40:1055–9.CrossRefPubMedGoogle Scholar
Singer CF, Hudelist G, Lamm W, Mueller R, Handl C, Kubista E, et al. Active (p)CrkL is overexpressed in human malignancies: potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncol Rep. 2006;15:353–9.PubMedGoogle Scholar
Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, et al. Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK. Nat Struct Mol Biol. 2007;14:503–10.CrossRefPubMedGoogle Scholar
Graf R, Barbero S, Keller N, Chen L, Uryu S, Schlaepfer D, et al. Src-inducible association of CrkL with procaspase-8 promotes cell migration. Cell Adh Migr. 2013;7:362–9.CrossRefPubMedPubMedCentralGoogle Scholar
Liu CH, Chen TC, Chau GY, Jan YH, Chen CH, Hsu CN, et al. Analysis of protein-protein interactions in cross-talk pathways reveals CRKL protein as a novel prognostic marker in hepatocellular carcinoma. Mol Cell Proteomics. 2013;12:1335–49.CrossRefPubMedPubMedCentralGoogle Scholar
Kim YH, Kwei KA, Girard L, Salari K, Kao J, Pacyna-Gengelbach M, et al. Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer. Oncogene. 2010;29:1421–30.CrossRefPubMedGoogle Scholar