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Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.

Zhu Z, Yu W, Fu X, Sun M, Wei Q, Li D, Chen H, Xiang J, Li H, Zhang Y, Zhao W, Zhao K - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). p-EGFR expression was correlated statistically with all of the other phosphorylated markers.Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS.Increased expression of p-AKT1 was associated with decreased patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.

ABSTRACT

Background: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).

Results: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.

Conclusion: Activation of AKT1 was associated with poor prognosis in ESCC.

No MeSH data available.


Related in: MedlinePlus

Log-rank tests of overall survival comparing patients with p-AKT1 H-scores of ≥70 and those with p-AKT1 H-scores of <70 for (a) all patients (n = 270; P < 0.001); b stage I-II patients (n = 128; P < 0.001); and c stage III patients (n = 142; P < 0.001)
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Fig3: Log-rank tests of overall survival comparing patients with p-AKT1 H-scores of ≥70 and those with p-AKT1 H-scores of <70 for (a) all patients (n = 270; P < 0.001); b stage I-II patients (n = 128; P < 0.001); and c stage III patients (n = 142; P < 0.001)

Mentions: At a median follow-up time of 34 months (range: 2–125 months), the median OS for the entire cohort was 39 months (95 % confidence interval [CI]: 20–58 months), and survival rates were 52.5 % at 3 years and 45.2 % at 5 years (Fig. 2). The variables tested on univariate analysis showed that the factors that were significantly associated with OS included gender, N stage, adjuvant therapy, and expression of p-AKT1 (Table 4). On multivariate analysis, gender, N stage, and p-AKT1 expression were found to be the independent prognostic factors for OS (Table 4). When expression of p-AKT1 increased, patients’ survival duration decreased (HR: 2.682, 95 % CI: 1.891–3.802). Log-rank tests of overall survival comparing patients with p-AKT1 high expression (H-scores ≥ 70) and those with p-AKT1 low expression (H-scores < 70) show that the group with p-AKT1 low expression had significantly better OS than did the group with high expression among all patients (P < 0.001, Fig. 3a), patients with stage I-II diease (P < 0.001, Fig. 3b) and patients with stage III disease (P < 0.001, Fig. 3c).Fig. 2


Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.

Zhu Z, Yu W, Fu X, Sun M, Wei Q, Li D, Chen H, Xiang J, Li H, Zhang Y, Zhao W, Zhao K - J. Exp. Clin. Cancer Res. (2015)

Log-rank tests of overall survival comparing patients with p-AKT1 H-scores of ≥70 and those with p-AKT1 H-scores of <70 for (a) all patients (n = 270; P < 0.001); b stage I-II patients (n = 128; P < 0.001); and c stage III patients (n = 142; P < 0.001)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559941&req=5

Fig3: Log-rank tests of overall survival comparing patients with p-AKT1 H-scores of ≥70 and those with p-AKT1 H-scores of <70 for (a) all patients (n = 270; P < 0.001); b stage I-II patients (n = 128; P < 0.001); and c stage III patients (n = 142; P < 0.001)
Mentions: At a median follow-up time of 34 months (range: 2–125 months), the median OS for the entire cohort was 39 months (95 % confidence interval [CI]: 20–58 months), and survival rates were 52.5 % at 3 years and 45.2 % at 5 years (Fig. 2). The variables tested on univariate analysis showed that the factors that were significantly associated with OS included gender, N stage, adjuvant therapy, and expression of p-AKT1 (Table 4). On multivariate analysis, gender, N stage, and p-AKT1 expression were found to be the independent prognostic factors for OS (Table 4). When expression of p-AKT1 increased, patients’ survival duration decreased (HR: 2.682, 95 % CI: 1.891–3.802). Log-rank tests of overall survival comparing patients with p-AKT1 high expression (H-scores ≥ 70) and those with p-AKT1 low expression (H-scores < 70) show that the group with p-AKT1 low expression had significantly better OS than did the group with high expression among all patients (P < 0.001, Fig. 3a), patients with stage I-II diease (P < 0.001, Fig. 3b) and patients with stage III disease (P < 0.001, Fig. 3c).Fig. 2

Bottom Line: Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). p-EGFR expression was correlated statistically with all of the other phosphorylated markers.Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS.Increased expression of p-AKT1 was associated with decreased patient survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China. zfeizhu@aliyun.com.

ABSTRACT

Background: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS).

Results: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival.

Conclusion: Activation of AKT1 was associated with poor prognosis in ESCC.

No MeSH data available.


Related in: MedlinePlus