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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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).</p><p>Conclusions</p><p>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.</p></div

Prognostic factors of Ovarian Cancer after resection (PFS).

<p>Prognostic factors of Ovarian Cancer after resection (PFS).</p

Correlation of eIF4G1 protein expression with the presence of omentum metastasis of ovarian cancer tissues used for eIF4G1 expression analysis.

<p>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.</p

Prognostic factors of Ovarian Cancer after resection (OS).

<p>Prognostic factors of Ovarian Cancer after resection (OS).</p

The mRNA expression of eIF4G1 in ovarian cancer tissues and normal ovary epithelial cell specimens.

<p>(A) Real-time RT PCR analysis of eIF4G1 in fresh frozen ovarian cancer samples and normal ovarian surface epithelial cell specimens in our study (P = 0.0375). (NORMAL:27 normal ovarian surface epithelial cell specimens;CANCER:40 frozen ovarian cancer samples). (B) Relative eIF4G1 mRNA expression of ovarian cancer samples and normal ovarian surface epithelial cells from the reported microarray data (accession number GSE18521) (P<0.0001; NORMAL: 10 normal ovarian tissues; CANCER: 53 snap-frozen ovarian cancer tissue specimens). (C) Relative eIF4G1 mRNA expression of ovarian cancer samples and normal ovarian surface epithelial cells from reported microarray data (accession number GSE40595; P = 0.0028; NORMAL: 6 normal ovarian surface epithelial cells; CANCER: 35 snap-frozen ovarian cancer tissue specimens). Scatter plot represents means ± SD.</p

The expression of eIF4G1 at the protein level in ovarian cancer tissues from patients.

<p><b>(Left, ×40; Right, ×100)</b> Immunohistochemical staining of eIF4G1 in ovarian cancer tissue at different staining score using anti-human eIF4G1 antibodies. (Left magnification, ×40; Right magnification, ×100).</p

Associations of cancerous eIF4G1 expression with clinicopathologic characteristics of ovarian cancer.

<p>Associations of cancerous eIF4G1 expression with clinicopathologic characteristics of ovarian cancer.</p

Correlation of eIF4G1 protein expression with clinicopathological stage of ovarian cancer tissues used for eIF4G1 expression analysis.

<p>Immunohistochemical analysis of eIF4G1 with stage I and II of ovarian cancer samples (n = 31) and stage III and IV of ovarian cancer samples (n = 102). P = 0.004.</p

Baseline Characteristics of the 134 Patients of Serous Ovarian Cancer.

<p>Baseline Characteristics of the 134 Patients of Serous Ovarian Cancer.</p

Summary of relative eIF4G1 protein expression in normal and ovarian cancer specimens assessed by IHC.

<p>Intensity of eIF4G1 staining was scored from 1 to 4, and an individual box plot was generated to display the distribution of the intensity of eIF4G1 staining for normal ovary samples and ovarian cancer specimens. Immunohistochemical analysis of eIF4G1 in FFPE ovarian cancer samples (n = 134) and normal FFPE ovarian surface epithelial specimens (n = 18). P = 0.0007. (NORMAL: normal FFPE ovarian surface epithelial specimens; CANCER: FFPE ovarian cancer samples).</p