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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

Kaplan-Meier plot for disease-free survival (DFS) and overall survival (OS) categorized based on annexin A2 (ANXA2) and annexin A4 (ANXA4) protein expression. High ANXA2 expression was associated with short DFS (p = 0.004) (a) but not with short OS (p = 0.245) (d). High ANXA4 expression was associated with short DFS (p = 0.033) (b) and OS (p = 0.032) (e). The association between high ANXA2/ANXA4 expression with DFS (c) and OS (f) was significantly different from that of low ANXA2/ANXA4 expression (p < 0.001 and p = 0.017, respectively). P-values were obtained from log-rank tests
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Fig4: Kaplan-Meier plot for disease-free survival (DFS) and overall survival (OS) categorized based on annexin A2 (ANXA2) and annexin A4 (ANXA4) protein expression. High ANXA2 expression was associated with short DFS (p = 0.004) (a) but not with short OS (p = 0.245) (d). High ANXA4 expression was associated with short DFS (p = 0.033) (b) and OS (p = 0.032) (e). The association between high ANXA2/ANXA4 expression with DFS (c) and OS (f) was significantly different from that of low ANXA2/ANXA4 expression (p < 0.001 and p = 0.017, respectively). P-values were obtained from log-rank tests

Mentions: The estimated five-year DFS and OS rates for the whole group were 87 % (95 % confidence interval [CI] 83–91) and 96 % (95 % CI, 93–98), respectively. ANXA2 and ANXA4 expression was significantly associated with poor DFS (p = 0.004 and p = 0.033, respectively) and OS (p = 0.245 and p = 0.032, respectively) (Fig. 4). The 5-year DFS rates were 80 and 81 % in patients with positive ANXA2 and ANXA4 expression, respectively, compared with 92 and 91 % in patients with negative expression. Similarly, 5-year OS rates were 94 and 94 % in patients with positive ANXA2 and ANXA4 expression respectively, compared with 97 and 97 % for patients with negative expressions. The combination of markers showed even greater discriminatory power and identified subgroups with 5-year DFS rates of 71 % vs. 95 % and 5-year OS rates of 91 % vs. 98 % using the ANXA2 and ANXA4 combination. The Cox proportional hazards model showed that expression of ANXA2 and combined ANXA2/ANXA4 expression remained an independent prognostic factor for DFS (hazard ratio [HR] = 2.72, 95 % CI, 1.41–5.27, p = 0.003; HR = 2.69, 95 % CI, 1.05–6.90, p = 0.039, respectively) (Table 2, Additional file 2: Table S1).Fig. 4


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)

Kaplan-Meier plot for disease-free survival (DFS) and overall survival (OS) categorized based on annexin A2 (ANXA2) and annexin A4 (ANXA4) protein expression. High ANXA2 expression was associated with short DFS (p = 0.004) (a) but not with short OS (p = 0.245) (d). High ANXA4 expression was associated with short DFS (p = 0.033) (b) and OS (p = 0.032) (e). The association between high ANXA2/ANXA4 expression with DFS (c) and OS (f) was significantly different from that of low ANXA2/ANXA4 expression (p < 0.001 and p = 0.017, respectively). P-values were obtained from log-rank tests
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Related In: Results  -  Collection

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Fig4: Kaplan-Meier plot for disease-free survival (DFS) and overall survival (OS) categorized based on annexin A2 (ANXA2) and annexin A4 (ANXA4) protein expression. High ANXA2 expression was associated with short DFS (p = 0.004) (a) but not with short OS (p = 0.245) (d). High ANXA4 expression was associated with short DFS (p = 0.033) (b) and OS (p = 0.032) (e). The association between high ANXA2/ANXA4 expression with DFS (c) and OS (f) was significantly different from that of low ANXA2/ANXA4 expression (p < 0.001 and p = 0.017, respectively). P-values were obtained from log-rank tests
Mentions: The estimated five-year DFS and OS rates for the whole group were 87 % (95 % confidence interval [CI] 83–91) and 96 % (95 % CI, 93–98), respectively. ANXA2 and ANXA4 expression was significantly associated with poor DFS (p = 0.004 and p = 0.033, respectively) and OS (p = 0.245 and p = 0.032, respectively) (Fig. 4). The 5-year DFS rates were 80 and 81 % in patients with positive ANXA2 and ANXA4 expression, respectively, compared with 92 and 91 % in patients with negative expression. Similarly, 5-year OS rates were 94 and 94 % in patients with positive ANXA2 and ANXA4 expression respectively, compared with 97 and 97 % for patients with negative expressions. The combination of markers showed even greater discriminatory power and identified subgroups with 5-year DFS rates of 71 % vs. 95 % and 5-year OS rates of 91 % vs. 98 % using the ANXA2 and ANXA4 combination. The Cox proportional hazards model showed that expression of ANXA2 and combined ANXA2/ANXA4 expression remained an independent prognostic factor for DFS (hazard ratio [HR] = 2.72, 95 % CI, 1.41–5.27, p = 0.003; HR = 2.69, 95 % CI, 1.05–6.90, p = 0.039, respectively) (Table 2, Additional file 2: Table S1).Fig. 4

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