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

Choi CH, Chung JY, Chung EJ, Sears JD, Lee JW, Bae DS, Hewitt SM - BMC Cancer (2016)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.

ABSTRACT

Background: The 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.

Methods: ANXA2 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.

Results: ANXA2 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).

Conclusions: These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.

No MeSH data available.


Related in: MedlinePlus

Association between chemoradiation response and annexin A2 (ANXA2) and annexin A4 (ANXA4) expression. ANXA4 expression was significantly correlated with resistance to chemoradiation (p = 0.029) (b), whereas ANXA2 expression was not (a)
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Fig3: Association between chemoradiation response and annexin A2 (ANXA2) and annexin A4 (ANXA4) expression. ANXA4 expression was significantly correlated with resistance to chemoradiation (p = 0.029) (b), whereas ANXA2 expression was not (a)

Mentions: ANXA2 expression was associated with a more aggressive cancer phenotype (Table 1). High ANXA2 expression was positively correlated with higher stage, large-sized tumors, lymphovascular space invasion, stromal invasion depth, lymph node metastasis, and parametrial involvement (p = 0.002, p = 0.01, p = 0.019, p < 0.001, p = 0.002, and p = 0.031, respectively). In contrast, ANXA4 expression was not associated with an aggressive phenotype, although it was more highly expressed in cancer tissue compared with normal tissue. To examine the association between ANX protein expression and chemo and/or radiotherapy resistance, we grouped patients receiving radiotherapy and/or chemotherapy into “resistant” (recurred within 3 years) or “sensitive” (no recurrence within 3 years) groups. As shown in Fig. 3, ANXA4 expression was significantly correlated with resistance to chemotherapy and/or radiation (p = 0.029).Fig. 3


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

Choi CH, Chung JY, Chung EJ, Sears JD, Lee JW, Bae DS, Hewitt SM - BMC Cancer (2016)

Association between chemoradiation response and annexin A2 (ANXA2) and annexin A4 (ANXA4) expression. ANXA4 expression was significantly correlated with resistance to chemoradiation (p = 0.029) (b), whereas ANXA2 expression was not (a)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940752&req=5

Fig3: Association between chemoradiation response and annexin A2 (ANXA2) and annexin A4 (ANXA4) expression. ANXA4 expression was significantly correlated with resistance to chemoradiation (p = 0.029) (b), whereas ANXA2 expression was not (a)
Mentions: ANXA2 expression was associated with a more aggressive cancer phenotype (Table 1). High ANXA2 expression was positively correlated with higher stage, large-sized tumors, lymphovascular space invasion, stromal invasion depth, lymph node metastasis, and parametrial involvement (p = 0.002, p = 0.01, p = 0.019, p < 0.001, p = 0.002, and p = 0.031, respectively). In contrast, ANXA4 expression was not associated with an aggressive phenotype, although it was more highly expressed in cancer tissue compared with normal tissue. To examine the association between ANX protein expression and chemo and/or radiotherapy resistance, we grouped patients receiving radiotherapy and/or chemotherapy into “resistant” (recurred within 3 years) or “sensitive” (no recurrence within 3 years) groups. As shown in Fig. 3, ANXA4 expression was significantly correlated with resistance to chemotherapy and/or radiation (p = 0.029).Fig. 3

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, MSC 1500, Bethesda, MD, 20892, USA.

ABSTRACT

Background: The 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.

Methods: ANXA2 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.

Results: ANXA2 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).

Conclusions: These findings indicate that detecting ANXA2 and ANXA4 expression may aid the evaluation of cervical carcinoma prognosis.

No MeSH data available.


Related in: MedlinePlus