CGB and GNRH1 expression analysis as a method of tumor cells metastatic spread detection in patients with gynecological malignances

Mirosław Andrusiewicz,Maria Wołuń-Cholewa,Wojciech Warchoł,Krystyna Adamska,Anna Jankowska,Emilia Gąsiorowska,Anna Szczerba,Ewa Nowak-Markwitz

doi:10.1186/1479-5876-9-130

Abstract

BackgroundMetastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression. Most cancer cells are localized in the primary tumor and only a small population of circulating tumor cells (CTC) has metastatic potential. CTC amount reflects the aggressiveness of tumors, therefore their detection can be used to determine the prognosis and treatment of cancer patients.The aim of this study was to evaluate human chorionic gonadotropin beta subunit (CGB) and gonadoliberin type 1 (GNRH1) expression as markers of tumor cells circulating in peripheral blood of gynecological cancer patients, indicating the metastatic spread of tumor.MethodsCGB and GNRH1 expression level in tumor tissue and blood of cancer patients was assessed by real-time RT-PCR. The data was analyzed using the Mann-Whitney U and Spearman tests. In order to distinguish populations with homogeneous genes' expression the maximal likelihood method for one- and multiplied normal distribution was used.ResultReal time RT-PCR results revealed CGB and GNRH1 genes activity in both tumor tissue and blood of gynecological cancers patients. While the expression of both genes characterized all examined tumor tissues, in case of blood analysis, the transcripts of GNRH1 were found in all cancer patients while CGB were present in 93% of patients. CGB and GNRH1 activity was detected also in control group, which consisted of tissue lacking cancerous changes and blood of healthy volunteers. The log-transformation of raw data fitted to multiplied normal distribution model showed that CGB and GNRH1 expression is heterogeneous and more than one population can be distinguished within defined groups.Based on CGB gene activity a critical value indicating the presence of cancer cells in studied blood was distinguished. In case of GNRH1 this value was not established since the results of the gene expression in blood of cancer patients and healthy volunteers were overlapping. However one subpopulation consists of cancer patient with much higher GNRH1 expression than in control group was found.ConclusionsAssessment of CGB and GNRH1 expression level in cancer patients' blood may be useful for indicating metastatic spread of tumor cells.

Highlights

Metastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression
We have previously demonstrated that the expression of chorionic gonadotropin beta subunit (CGB) in endometrial cancer as well as in endometrial atypical hyperplasia is accompanied by expression of gonadotopin releasing-hormone type 1 [38]
In this study we showed that the up-regulation of human chorionic gonadotropin beta subunit and gonadoliberin type 1 genes expression may indicate the presence of tumor cells circulating in peripheral blood of gynecological cancer patients

Summary

Introduction

Metastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression. Most cancer cells are localized in the primary tumor and only a small population of circulating tumor cells (CTC) has metastatic potential. The accumulation of genetic alternations increases genetic instability [4] During this process several different cell lines with different gene expression profile might co-exist within one tumor [5,6,7,8,9,10]. Cancer cells and their metastatic progeny retain the capacity for self-evolution [1]. New cell variants are better adapted to local growth requirements and might survive or undergo apoptosis [11,12]

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