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

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

The mRNA expression of eIF4G1 in ovarian cancer tissues and normal ovary epithelial cell specimens.(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.
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pone.0163447.g001: The mRNA expression of eIF4G1 in ovarian cancer tissues and normal ovary epithelial cell specimens.(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.

Mentions: We examined 40 serous ovarian cancer specimens and 27 normal OSE specimens using quantitative RT-PCR for mRNA and analyzed the difference in the eIF4G1 mRNA expression between the tumor and the normal OSE specimens. To accurately evaluate the expression levels of eIF4G1 mRNA, the included samples for RT-PCR contain at least 70% of tumor cell nuclei. The expression of eIF4G1 was markedly higher in the serous ovarian cancer specimens than in normal OSE specimens as shown in Fig 1A (P = 0.0375). Besides, we compared the eIF4G1 mRNA expression of ovarian cancer tissues and normal ovarian surface epithelial cells from the microarray data (GEO accession numbers GSE18521 [12] and GSE40595 [13]). The expression of eIF4G1 was also higher in the serous ovarian cancer specimens (GSE18521: P<0.0001; GSE40595: P = 0.0028) as shown in Fig 1B and 1C.


Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer
The mRNA expression of eIF4G1 in ovarian cancer tissues and normal ovary epithelial cell specimens.(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.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036801&req=5

pone.0163447.g001: The mRNA expression of eIF4G1 in ovarian cancer tissues and normal ovary epithelial cell specimens.(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.
Mentions: We examined 40 serous ovarian cancer specimens and 27 normal OSE specimens using quantitative RT-PCR for mRNA and analyzed the difference in the eIF4G1 mRNA expression between the tumor and the normal OSE specimens. To accurately evaluate the expression levels of eIF4G1 mRNA, the included samples for RT-PCR contain at least 70% of tumor cell nuclei. The expression of eIF4G1 was markedly higher in the serous ovarian cancer specimens than in normal OSE specimens as shown in Fig 1A (P = 0.0375). Besides, we compared the eIF4G1 mRNA expression of ovarian cancer tissues and normal ovarian surface epithelial cells from the microarray data (GEO accession numbers GSE18521 [12] and GSE40595 [13]). The expression of eIF4G1 was also higher in the serous ovarian cancer specimens (GSE18521: P<0.0001; GSE40595: P = 0.0028) as shown in Fig 1B and 1C.

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