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Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer

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ABSTRACT

Background: Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients.

Methods: We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer.

Results: The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026).

Conclusions: These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer.

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Correlation of eIF4G1 protein expression with the presence of omentum metastasis of ovarian cancer tissues used for eIF4G1 expression analysis.Immunohistochemical analysis of eIF4G1 without omentum metastasis of ovarian cancer samples (n = 46) and with omentum metastasis of ovarian cancer samples (n = 86). P = 0.024.
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pone.0163447.g005: Correlation of eIF4G1 protein expression with the presence of omentum metastasis of ovarian cancer tissues used for eIF4G1 expression analysis.Immunohistochemical analysis of eIF4G1 without omentum metastasis of ovarian cancer samples (n = 46) and with omentum metastasis of ovarian cancer samples (n = 86). P = 0.024.

Mentions: The mean value of staining H score in cancer tissue microarrays is 4 and the cutoff value was identified as the mean value. So a staining H score of ≥4 was used to define tumors with high eIF4G1expression, and a score of <4 indicated low eIF4G1 expression. A correlation was observed between eIF4G1 cytoplasmic expression and the pathological parameters of 134 cases of ovarian cancer (Table 2). In univariate analyses, as shown in Fig 4, lower expression of eIF4G1 protein was exhibited in early–stage ovarian cancer (FIGO stages I and II) while higher expression in advanced stage ovarian cancer (FIGO stages III and IV) tissues. (P = 0.004). In addition, a moderate but significant correlation between the level of eIF4G1 protein level and omentum metastasis was also observed (P = 0.024) (Fig 5). However, as summarized in Table 2, no remarkable correlations were detected between the expression level of eIF4G1 protein and patient age, degree of differentiation, optimal or suboptimal cytoreduction, response to chemotherapy or the serum of CA-125 in patients with ovarian cancer. In multivariate analyses, tumor stage (hazard ratio,0.349; 95% CI, 0.549 to 1.587;P = 0.012), a resistant or refractory chemoresponse (hazard ratio,8.579; 95% CI, 4.02to 18.29; P<0.0001for PFS and hazard ratio,6.76; 95% CI, 3.49 to 13.07; P<0.0001 for OS) and cytoreduction (hazard ratio,3.21; 95% CI, 1.74 to 5.92; P<0.0001 for PFS and hazard ratio,2.3; 95% CI, 1.29 to 4.08; P = 0.005 for OS) were associated with poor survival. However, after adjusting for other risk factors (age, tumor stage, chemosensitivity and cytoreduction), the eIF4G1 expression level was not an independent prognostic factor for OS (hazard ratio, 0.985; 95% CI, 0.524 to 1.85; P = 0.96) and PFS (hazard ratio, 1.235; 95% CI, 0.64 to 2.37; P = 0.53). Moreover, other clinicopathological characteristics including age, omentum and CA125 level were not independent prognostic markers for ovarian cancer (Tables 3 and 4).


Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer
Correlation of eIF4G1 protein expression with the presence of omentum metastasis of ovarian cancer tissues used for eIF4G1 expression analysis.Immunohistochemical analysis of eIF4G1 without omentum metastasis of ovarian cancer samples (n = 46) and with omentum metastasis of ovarian cancer samples (n = 86). P = 0.024.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5036801&req=5

pone.0163447.g005: Correlation of eIF4G1 protein expression with the presence of omentum metastasis of ovarian cancer tissues used for eIF4G1 expression analysis.Immunohistochemical analysis of eIF4G1 without omentum metastasis of ovarian cancer samples (n = 46) and with omentum metastasis of ovarian cancer samples (n = 86). P = 0.024.
Mentions: The mean value of staining H score in cancer tissue microarrays is 4 and the cutoff value was identified as the mean value. So a staining H score of ≥4 was used to define tumors with high eIF4G1expression, and a score of <4 indicated low eIF4G1 expression. A correlation was observed between eIF4G1 cytoplasmic expression and the pathological parameters of 134 cases of ovarian cancer (Table 2). In univariate analyses, as shown in Fig 4, lower expression of eIF4G1 protein was exhibited in early–stage ovarian cancer (FIGO stages I and II) while higher expression in advanced stage ovarian cancer (FIGO stages III and IV) tissues. (P = 0.004). In addition, a moderate but significant correlation between the level of eIF4G1 protein level and omentum metastasis was also observed (P = 0.024) (Fig 5). However, as summarized in Table 2, no remarkable correlations were detected between the expression level of eIF4G1 protein and patient age, degree of differentiation, optimal or suboptimal cytoreduction, response to chemotherapy or the serum of CA-125 in patients with ovarian cancer. In multivariate analyses, tumor stage (hazard ratio,0.349; 95% CI, 0.549 to 1.587;P = 0.012), a resistant or refractory chemoresponse (hazard ratio,8.579; 95% CI, 4.02to 18.29; P<0.0001for PFS and hazard ratio,6.76; 95% CI, 3.49 to 13.07; P<0.0001 for OS) and cytoreduction (hazard ratio,3.21; 95% CI, 1.74 to 5.92; P<0.0001 for PFS and hazard ratio,2.3; 95% CI, 1.29 to 4.08; P = 0.005 for OS) were associated with poor survival. However, after adjusting for other risk factors (age, tumor stage, chemosensitivity and cytoreduction), the eIF4G1 expression level was not an independent prognostic factor for OS (hazard ratio, 0.985; 95% CI, 0.524 to 1.85; P = 0.96) and PFS (hazard ratio, 1.235; 95% CI, 0.64 to 2.37; P = 0.53). Moreover, other clinicopathological characteristics including age, omentum and CA125 level were not independent prognostic markers for ovarian cancer (Tables 3 and 4).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients.

Methods: We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer.

Results: The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026).

Conclusions: These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer.

No MeSH data available.


Related in: MedlinePlus