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A panel of overexpressed proteins for prognosis in esophageal squamous cell carcinoma.

Shang L, Liu HJ, Hao JJ, Jiang YY, Shi F, Zhang Y, Cai Y, Xu X, Jia XM, Zhan QM, Wang MR - PLoS ONE (2014)

Bottom Line: Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426).Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001).Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621-2.696, P = 0.00000001).

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. In order to identify useful biomarkers for accurately classifying prognostic risks for ESCC patients, we examined the expression of six proteins by immunohistochemistry (IHC) in 590 paraffin-embedded ESCC samples. The candidate proteins include p53, EGFR, c-KIT, TIMP1 and PI3K-p110α reported to be altered in ESCC tissues as well as another important component of PI3K, PI3K-p85α. Of the six proteins tested, p53, EGFR, c-KIT, TIMP1 and PI3K-p85α were detected with high expression in 43.0%, 36.6%, 55.9%, 70.7% and 57.1% of tumors, respectively. Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426). Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001). Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621-2.696, P = 0.00000001). The data suggest that the three-protein panel of PI3K-p85α, EGFR and p53 is an important candidate biomarker for the prognosis of patients with ESCC.

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Representative IHC images of PI3K-P85α, EGFR, and p53 in the serial tissue sections.Expression of these proteins in 3 cases (EC-440, EC-452, EC-586). PI3K, phosphatidylinositol 3-kinases; EGFR, epidermal growth factor receptor. Original magnification: 400×.
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pone-0111045-g004: Representative IHC images of PI3K-P85α, EGFR, and p53 in the serial tissue sections.Expression of these proteins in 3 cases (EC-440, EC-452, EC-586). PI3K, phosphatidylinositol 3-kinases; EGFR, epidermal growth factor receptor. Original magnification: 400×.

Mentions: In the first cohort, high expression of PI3K-p85α (P = 0.02231), EGFR (P = 0.00101) and p53 (P = 0.04439) were associated with poor survivals in ESCCs, whereas no correlation was found between the abnormalities of TIMP1 or c-KIT and prognosis (Figure 3A). In the second cohort, high expression of PI3K-p85α and p53 also contributed to a poorer survival (P = 0.02861, 0.04054), whereas overexpression of EGFR (P = 0.08831) was not significantly correlated with a shorter overall survival (Figure 3B). Based on the consistency of Kaplan-Meier plots of patients with ESCC in the two cohorts, the clinical data from the two groups of samples were combined into a single database to test prognostic value of PI3K-p85α, EGFR and p53. There was a significant correlation between high expression of PI3K-p85α, EGFR and p53 and the overall survival (P = 0.00111, 0.00001, 0.00426, Figure 3C). Stratified analysis indicated that high expression of p53 was correlated with short overall survival in pN0 (P = 0.010) and stage I/IIA (P = 0.005), EGFR in pN0 (P = 0.003), pN1 (P = 0.002) and stage IIB/III (P = 0.00005) and PI3K-p85α in pN1 (P = 0.00007) and stage IIB/III (P = 0.001). Representative immunohistochemical images of PI3K-P85α, EGFR and p53 expressions in the same regions were shown in Figure 4. Especially, the three-protein panel (PI3K-P85α, EGFR and p53) could divide the patients into subgroups with different prognosis in both the two cohorts or together (P = 0.00016, 0.00020, <0.00001, Figure 5A–C). Patients with high expression of two or three proteins had a much poorer prognosis compared with those with zero or one high marker (P = 0.00001, Figure 5D).


A panel of overexpressed proteins for prognosis in esophageal squamous cell carcinoma.

Shang L, Liu HJ, Hao JJ, Jiang YY, Shi F, Zhang Y, Cai Y, Xu X, Jia XM, Zhan QM, Wang MR - PLoS ONE (2014)

Representative IHC images of PI3K-P85α, EGFR, and p53 in the serial tissue sections.Expression of these proteins in 3 cases (EC-440, EC-452, EC-586). PI3K, phosphatidylinositol 3-kinases; EGFR, epidermal growth factor receptor. Original magnification: 400×.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206450&req=5

pone-0111045-g004: Representative IHC images of PI3K-P85α, EGFR, and p53 in the serial tissue sections.Expression of these proteins in 3 cases (EC-440, EC-452, EC-586). PI3K, phosphatidylinositol 3-kinases; EGFR, epidermal growth factor receptor. Original magnification: 400×.
Mentions: In the first cohort, high expression of PI3K-p85α (P = 0.02231), EGFR (P = 0.00101) and p53 (P = 0.04439) were associated with poor survivals in ESCCs, whereas no correlation was found between the abnormalities of TIMP1 or c-KIT and prognosis (Figure 3A). In the second cohort, high expression of PI3K-p85α and p53 also contributed to a poorer survival (P = 0.02861, 0.04054), whereas overexpression of EGFR (P = 0.08831) was not significantly correlated with a shorter overall survival (Figure 3B). Based on the consistency of Kaplan-Meier plots of patients with ESCC in the two cohorts, the clinical data from the two groups of samples were combined into a single database to test prognostic value of PI3K-p85α, EGFR and p53. There was a significant correlation between high expression of PI3K-p85α, EGFR and p53 and the overall survival (P = 0.00111, 0.00001, 0.00426, Figure 3C). Stratified analysis indicated that high expression of p53 was correlated with short overall survival in pN0 (P = 0.010) and stage I/IIA (P = 0.005), EGFR in pN0 (P = 0.003), pN1 (P = 0.002) and stage IIB/III (P = 0.00005) and PI3K-p85α in pN1 (P = 0.00007) and stage IIB/III (P = 0.001). Representative immunohistochemical images of PI3K-P85α, EGFR and p53 expressions in the same regions were shown in Figure 4. Especially, the three-protein panel (PI3K-P85α, EGFR and p53) could divide the patients into subgroups with different prognosis in both the two cohorts or together (P = 0.00016, 0.00020, <0.00001, Figure 5A–C). Patients with high expression of two or three proteins had a much poorer prognosis compared with those with zero or one high marker (P = 0.00001, Figure 5D).

Bottom Line: Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426).Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001).Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621-2.696, P = 0.00000001).

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. In order to identify useful biomarkers for accurately classifying prognostic risks for ESCC patients, we examined the expression of six proteins by immunohistochemistry (IHC) in 590 paraffin-embedded ESCC samples. The candidate proteins include p53, EGFR, c-KIT, TIMP1 and PI3K-p110α reported to be altered in ESCC tissues as well as another important component of PI3K, PI3K-p85α. Of the six proteins tested, p53, EGFR, c-KIT, TIMP1 and PI3K-p85α were detected with high expression in 43.0%, 36.6%, 55.9%, 70.7% and 57.1% of tumors, respectively. Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426). Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001). Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621-2.696, P = 0.00000001). The data suggest that the three-protein panel of PI3K-p85α, EGFR and p53 is an important candidate biomarker for the prognosis of patients with ESCC.

Show MeSH
Related in: MedlinePlus