Prognostic significance of annexin A2 and annexin A4 expression in patients with cervical cancer

Abstract

BackgroundThe annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer.MethodsANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases and compared the data with clinicopathological variables, including the survival of cervical cancer patients.ResultsANXA2 expression was lower in cancer tissue (p = 0.002), whereas ANXA4 staining increased significantly in cancer tissues (p < 0.001). ANXA2 expression was more prominent in squamous cell carcinoma (p < 0.001), whereas ANXA4 was more highly expressed in adeno/adenosquamous carcinoma (p < 0.001). ANXA2 overexpression was positively correlated with advanced cancer phenotypes, whereas ANXA4 expression was associated with resistance to radiation with or without chemotherapy (p = 0.029). Notably, high ANXA2 and ANXA4 expression was significantly associated with shorter disease-free survival (p = 0.004 and p = 0.033, respectively). Multivariate analysis indicated that ANXA2+ (HR = 2.72, p = 0.003) and ANXA2+/ANXA4+ (HR = 2.69, p = 0.039) are independent prognostic factors of disease-free survival in cervical cancer. Furthermore, a random survival forest model using combined ANXA2, ANXA4, and clinical variables resulted in improved predictive power (mean C-index, 0.76) compared to that of clinical-variable-only models (mean C-index, 0.70) (p = 0.006).ConclusionsThese findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2459-y) contains supplementary material, which is available to authorized users.

S100A11 functions as novel oncogene in glioblastoma via S100A11/ANXA2/NF‐κB positive feedback loop

“…Annexin A2 (ANXA2), belongs to annexin family, is a calcium‐dependent phospholipid‐binding protein. ANXA2 is overexpressed in numerous tumours, including glioma . Aberrantly, expression of ANXA2 plays important roles in tumour development by regulating cell proliferation, apoptosis, invasion and metastasis …”

“…The S100 proteins are low molecular weight proteins (10)(11)(12) that belong to the EF-hand calcium-binding proteins family and are only expressed in vertebrates. 3,4 S100A11(known as calgizzarin or S100C) is a member of the S100 proteins.…”

“…ANXA2 is overexpressed in numerous tumours, including glioma. [11][12][13][14] Aberrantly, expression of ANXA2 plays important roles in tumour development by regulating cell proliferation, apoptosis, invasion and metastasis. 15 In this study, we investigated the roles of S100A11 in GBM tumorigenicity, particularly GBM cell proliferation, epithelial-mesenchymal transition (EMT), migration, invasion and neurosphere formation via silencing or overexpression in GBM.…”

Identifying Molecular Markers of Cervical Cancer Based on Competing Endogenous RNA Network Analysis

“…This study built a 12-gene-based prediction model, which performed well for the recurrence prediction of early cervical cancer [10]. Another study, using the same expression profile data, revealed that Annexin A2 (ANXA2) and ANXA4 are also molecular indicators of the recurrence risk of cervical cancer [11]. Overexpression of ANXA2 and ANXA4 is associated with shorter disease-free survival [11].…”

“…Another study, using the same expression profile data, revealed that Annexin A2 (ANXA2) and ANXA4 are also molecular indicators of the recurrence risk of cervical cancer [11]. Overexpression of ANXA2 and ANXA4 is associated with shorter disease-free survival [11]. However, additional molecular markers possibly exist and should be identified.…”