Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma.
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ABSTRACT:
SUBMITTER: Weichert W
PROVIDER: S-EPMC2410182 | biostudies-other | 2004 Feb
REPOSITORIES: biostudies-other
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Project description:BackgroundPD-L1 expression levels determined by immunostaining are known to be related to the survival rate and prognosis of patients with various types of cancers, as well as to the therapeutic response to immune checkpoint inhibitors. Recently, the U.S. Food and Drug Administration approved an immune checkpoint inhibitor for the treatment of non-small cell lung cancer along with the clones used for PD-L1 immunostaining to predict the resulting response. In this study, we performed PD-L1 immunostaining of tissue microarrays from ovarian epithelial cancer using SP263, an approved clone, and examined the effect of PD-L1 expression on survival rate and prognosis.MethodsTissue microarrays were constructed from ovarian epithelial cancer tissues of 248 patients and PD-L1 immunostaining was performed using the SP263 clone. PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were evaluated, and the effect of PD-L1 expression on survival and prognosis was analyzed.ResultsPD-L1 was detected in tumor cells as well as intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. It was most frequently expressed in stromal tumor-infiltrating lymphocytes. The Kaplan-Meier curve analysis and log rank test showed that only high stromal PD-L1 expression was associated with increased overall survival in ovarian serous carcinoma. Multivariate and univariate Cox regression analyses revealed that stromal PD-L1 expression was an independent prognostic factor, especially in ovarian serous carcinoma.ConclusionsPD-L1 immunostaining using SP263 was observed in tumor cells as well as intraepithelial and stromal tumor-infiltrating lymphocytes. PD-L1-expressing stromal tumor-infiltrating lymphocytes were associated with an increased overall survival rate and may serve as a favorable prognostic factor in ovarian cancer, particularly serous carcinoma.
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Project description:The putative oncogenic role of ATP/GTP binding protein like 2 (AGBL2) in catalyzing α-tubulin detyrosination has recently been characterized in cancer. However, the status of AGBL2 expression in ovarian cancer and its potential clinical and prognostic significance remain unclear. In the present study, immunohistochemistry staining investigated the protein expression level of AGBL2 in paraffin-embedded pathological specimens from 30 normal ovaries, 35 ovarian cystadenomas, 38 borderline ovarian tumors and 165 invasive ovarian carcinomas. The association between AGBL2 expression and clinicopathological characteristics of patients was evaluated using the χ2 test or Fisher's exact test. The survival status of patients was assessed by receiver-operator curve analysis. The results demonstrated that high expression of AGBL2 was observed in 9% of cystadenomas cases, 21% of borderline tumors cases and 38% of ovarian carcinomas cases; however AGBL2 expression was not high in normal ovarian tissues (P<0.01). Furthermore, the results demonstrated that high expression of AGBL2 was associated with tumor histological grade, advanced pT/pN/pM and cancer stage according to the International Federation of Gynecology and Obstetrics (P<0.05). Following univariate survival analysis of the ovarian carcinoma groups, high expression of AGBL2 was significantly associated with shorter patient survival (P<0.001). In addition, multivariate analysis revealed that AGBL2 could be identified as a potential independent prognostic factor for overall survival in patients with ovarian carcinoma (P=0.004). Furthermore, the results demonstrated that AGBL2 expression was significantly associated with the expression of immunity related GTPase M (IRGM) (P=0.013) and LC3A/B (P=0.004). IRGM expression level was also significantly associated with LC3A/B expression level (P=0.023). These findings demonstrated that AGBL2 expression was high in ovarian carcinomas, which suggested that AGBL2 may participate in the acquisition of an aggressive phenotype and may therefore serve as an independent prognostic molecular marker.
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Project description:We assessed the presence of vascular endothelial growth factor (VEGF)-C, VEGF-D and their receptor VEGFR-3 by immunohistochemistry in 59 epithelial ovarian carcinomas, 11 borderline tumours and 20 benign cystadenomas. VEGF-C and VEGF-D were generally expressed in tumour cells and also in endothelia adjacent to tumour nests which showed a strong staining for them. VEGFR-3 was expressed in lymphatic and vascular endothelial cells adjacent to tumour nests. Immunoreactivity was significantly more frequent as lesions progressed from a benign tumour to advanced carcinoma. A strong correlation was found between VEGF-C and VEGF-D detected in carcinoma and VEGFR-3 detected in neighbouring endothelial cells. Increased expression of VEGF-C, VEGF-D and VEGFR-3 was significantly associated with lymph node metastasis and peritoneal metastasis outside the pelvis. There was a significant correlation between the high levels of VEGF-C and VEGF-D proteins, and poor survival. The presence of VEGF-D was an independent prognostic indicator by multivariate analysis. We conclude that VEGF-C, VEGF-D and VEGFR-3 play an important role in lymphatic spread and intraperitoneal tumour development in ovarian carcinoma. Since VEGF-D was found to be an independent predictor of poor outcome, its measurement, together with other prognostic markers may improve prospective identification of patients with a poor prognosis.
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Project description:Polo-like kinase 1 (PLK1) has been suggested to serve as oncogene in most human cancers. The aim of our study is to present more evidence about the clinical and prognostic value of PLK1 in lung squamous cell carcinoma patients. The status of PLK1 was observed in lung adenocarcinoma, lung squamous cell carcinoma and normal lung tissues through analyzing microarray data set (GEO accession number: GSE1213 and GSE 3627). PLK1 mRNA and protein expressions were detected in lung squamous cell carcinoma and normal lung tissues by using qRT-PCR and immunohistochemistry. In our results, the levels of PLK1 in lung squamous cell carcinoma tissues were higher than that in lung adenocarcinoma tissues. Compared with paired adjacent normal lung tissues, the PLK1 expression was increased in lung squamous cell carcinoma tissues. Furthermore, high-expression of PLK1 protein was correlated with differentiated degree, clinical stage, tumor size, lymph node metastasis, and distant metastasis. The univariate and multivariate analyses showed PLK1 protein high-expression was an unfavorable prognostic biomarker for lung squamous cell carcinoma patients. In conclusion, High-expression of PLK1 is associated with the aggressive progression and poor prognosis in lung squamous cell carcinoma patients.
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Project description:BackgroundThe expression and function of ribosomal s6 protein kinase 4 (RSK4) in renal cell carcinoma (RCC) are unknown.MethodsImmunohistochemistry was used to detect the expression of RSK4 in RCC, and the relationship between RSK4 expression and clinicopathological features as well as prognosis of RCC patients was statistically analysed. Ectopic RSK4 expression in RCC cell lines was performed to determine its effect on cell cycle regulation, tumour invasiveness, and metastatic capability.ResultsRSK4 was overexpressed in RCCs (P=0.003), compared with normal tissues, and the expression varied in different RCC subtypes (P=0.021), especially in two subtypes of papillary RCCs (P=0.001). RSK4 expression was positively correlated with high pT stage (P<0.001), high Fuhrman grade (P<0.001), lymph node involvement (P<0.001), and presence of distant metastasis (P=0.039), and could predict poor outcome in RCC patients. Molecular studies showed that overexpression of RSK4 could promote cell cycle progression and enhance the invasive and metastatic capability of RCC cell lines and vice versa.ConclusionThe expression pattern and molecular mechanisms of RSK4 in RCCs indicate that it could be a potential independent prognostic factor and serve as a new potential therapeutic target for RCC patients.
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Project description:BACKGROUND:Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS:Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n =?20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n =?151). RESULTS:EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p =?0.014; Hazard ratio?=?2.951; 95% confidence interval: 1.240-7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p =?0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS:EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging.
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Project description:Polo-like kinase 4 (PLK4) promotes tumorigenesis and is associated with the prognosis of several solid tumors, while its clinical role in patients with renal cell carcinoma (RCC) remains unidentified. The present study aimed to analyze the association of PLK4 with clinicopathological characteristics and long-term prognosis in patients with RCC. The present study detected PLK4 protein and mRNA expression using immunohistochemical and reverse transcription-quantitative PCR assays in 120 patients with RCC. Disease-free survival (DFS) and overall survival (OS) time were calculated based on a median follow-up duration of 6.9 years (range, 1.2-9.9 years). PLK4 protein expression was elevated in tumor tissues compared with adjacent tissues (P<0.001). Upregulation of PLK4 protein was associated with increased T stage (P=0.023), N stage (P=0.014) and TNM stage (P=0.007). Additionally, elevated tumor PLK4 protein expression exhibited an associating trend (without statistical significance) with reduced DFS rate (P=0.066) and was associated with decreased OS rate (P=0.036). However, univariate Cox's regression analysis indicated that high PLK4 protein expression (compared with low PLK4 protein expression) was associated with reduced OS rate (P=0.040) but not with PFS rate (P=0.070). Following adjustment by multivariate Cox's regression analysis, PLK4 protein expression was associated with neither DFS nor OS rate (both P>0.050). Additionally, PLK4 mRNA expression was further detected in some patients (for which fresh specimens frozen in liquid nitrogen were available) to validate the aforementioned observations, and the expression was elevated in tumor tissues compared with adjacent tissues. Furthermore, increased PLK4 mRNA expression was associated with tumor size ≥7 cm, high TNM stage and reduced DFS rate (all P<0.050). PLK4 possesses a certain clinical utility in monitoring the clinical stage of patients with RCC, while its prognostic value requires further validation.
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