Gene expression of circulating tumour cells in breast cancer patients

Abstract

Background The diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC) need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC) could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation. Materials and methods We performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB) samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR. Results ga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3 * muc-1 and GA7 ga733.3 *muc-1* mgb1 * spdef . Conclusion Our study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3 * muc-1 and ga733.3 *3 muc-1 * mgb1 * spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.

Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

“…Haematological CTC are a prerequisite to distant organ metastasis in many cancer entities [ 7 , 32 - 34 ]. Several studies suggest that only a minority of tumor cells have the ability to invade and metastasize [ 35 - 37 ].…”

“…Tumor cells entering the circulation depend on the organ microenvironment in order to be able to colonize tissues and to proliferate [ 2 - 6 ]. One of the promising markers for a current risk classification system is the presence of circulating tumor cells (CTC) in the blood of tumor patients [ 7 ]. Braun et al [ 8 ] showed that the presence of micrometastasis in the bone marrow at the time of diagnosis of BC is an independent predictor of poor prognosis.…”

“…Also Benoy et al [ 9 ] described the presence of CK19+ disseminated tumor cells in the bone marrow by reverse transcriptase-PCR as an independent prognostic factor in untreated patients with BC [ 9 - 11 ]. In other studies the persistence of CTC after therapy showed a strong association with prognosis, particularly in women with hormone receptor-negative disease and adjuvant therapy [ 7 ].…”

Prostate-derived Ets factor, an oncogenic driver in breast cancer

“…32 Circulating tumor cells from breast cancer patients were also found to express PDEF. 13,33 Based on the oncogenic properties of PDEF, these findings support a continuing role for PDEF in breast cancer progression.…”

Μοριακή Διάγνωση Της Μικρομεταστατικής Νόσου Στον Καρκίνο Μαστού

“…Δπίζεο ην PBGD δελ έρεη βξεζεί λα έρεη ςεπδνγνλίδηα, κεηώλνληαο θαηά πνιύ ηνπο απαηηνύκελνπο πεηξακαηηθνύο ρεηξηζκνύο[289]. Ωζηόζν, ε έθθξαζε πνιιαπιώλ γνληδίσλ ζε ζρέζε κε ηελ έθθξαζε ελόο γνληδίνπ έρεη ην πιενλέθηεκα αύμεζεο ηεο επαηζζεζίαο αλίρλεπζεο ησλ CTCs θαη παξέρεη ζεκαληηθή πιεξνθνξία ζρεηηθά κε ηελ εηεξνγέλεηα ησλ CTCs[295]. Γηα πξώηε θνξά αλαπηύζζεηαη κεζνδνινγία ηεηξαπιήο πνζνηηθήο PCR γηα ηα γνλίδηα CK-19, HER-2, MAGE-A3 θαη PBGD.…”