Fyn-related kinase expression predicts favorable prognosis in patients with cervical cancer and suppresses malignant progression by regulating migration and invasion.
OBJECTIVE
To investigate expression pattern, clinical significance and potential roles of fyn related kinase (FRK) in cervical cancer.


METHODS
Expression of FRK protein and mRNA in 100 pairs of cervical cancer and matched non-cancerous tissue samples were detected by Western blot, immunohistochemistry and quantitative PCR, respectively. Statistical analyses were performed to evaluate associations of FRK protein expression with various clinicopathologic features and patients' prognosis. The effects of FRK on cell migration and invasion were examined using in vitro migration and invasion assays, respectively.


RESULTS
Weak/negative immunostaining of FRK protein was observed in 86 (86.00%) of 100 cervical cancer tissues. Low FRK expression was significantly associated with several aggressive clinicopathologic features of cervical cancer, such as higher International Federation of Gynecology and Obstetric stage (P=0.01), the presence of lymph node metastasis (P=0.01) and recurrence (P=0.02). In addition, the survival analysis showed that cervical cancer patients with low FRK expression often had shorter overall survival than those with high FRK expression. The multivariate analysis also identified FRK expression as an independent prognostic factor of cervical cancer. Functionally, the enforced expression of FRK could efficiently inhibit cell migration and invasion of cervical cancer cells, but the knockdown of FRK dramatically enhanced cell migration and invasion.


CONCLUSIONS
Our findings suggest that loss of FRK protein may be implicated into the tumorigenesis and cell motility of human cervical cancer. More importantly, FRK expression may function as a promising prognostic marker of this malignancy, highlighting its potentials as a candidate target for gene therapy.
Department of Radiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Xiaofeng
X
Zhang
Department of Gynecology & Tumor, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Fengshuang
F
Li
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: linzzhu_pku@163.com.
Prof Linzhong
PL
Zhu
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007044:Hysterectomy; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human
Cervical cancer; Clinicopathologic feature; Fyn related kinase; Invasion; Migration; Prognosis