Prognostički značaj biomarkera epitelno-mezenhimalne tranzicije kod metastatskog kolorektalnog karcinoma u jetri

Abstract

Uvod: Postoji malo podataka o ekspresiji markera epitelno-mezenhimalne tranzicije (EMT) kod bolesnika sa metastazama kolorektalnog karcinoma u jetri. Prognostički značaj markera EMT u predikciji brze progresije bolesti nakon tretmana sa kurativnom namerom je i dalje nerasvetljen. Ciljevi: Proceniti ekspresiju i prognostički značaj CDH1, FN1 i VIM kod bolesnika sa metastazama kolorektalnog karcinoma u jetri nakon resekcije jetre sa kurativnom namerom. Metodologija: U ovu prospektivnu pilot studiju uključeno je trideset bolesnika sa metastazama kolorektalnog karcinoma u jetri lečenih resekcijom jetre sa kurativnom namerom. Prikupljeni su uzorak krvi, maligno metastatsko tkivo u jetri i netumorsko tkivo jetre neposredno uz metastazu. Ekspresija CDH1, FN1 i VIM je analizirana kvantitativnom lančanom reakcijom polimeraze u realnom vremenu. Vrednosti su poređene između grupa formiranih prema različitim kliničko-patološkim karakteristikama. Rezultati: Ekspresija CDH1 je bila slična u malignom metastatskom tkivu jetre i netumorskom tkivu, dok je ekspresija FN1 i VIM bila značajno niža u metastatskom kivu (p=0.003 i p<0.001, respektivno). Serumska ekspresija CDH1 i VIM je detektovana kod 66.7% i 93.3% bolesnika, respektivno, dok FN1 nije detektovan ni kod jednog bolesnika. Korelacija CDH1 i VIM ekspresije između seruma i malignog metastatskog tkiva u jetri nije statistički značajna. Snižena ekspresija CDH1 u malignom metatstatskom tkivu i snižena ekspresija VIM u serumu su bile udružene sa ranim recidivom nakon hirurškog tretmana metastaza kolorektalnog karcinoma u jetri. Ekspresija CDH1 u malignom metatstatskom tkivu je nezavisni prediktor ranog recidiva godinu dana nakon resekcije jetre. Zaključak: Snižena ekspresija CDH1 u malignom metastatskom tkivu jetre i snižena ekspresija VIM u serumu su udružene sa ranim recidivom nakon resekcije jetre zbog metastaza kolorektalnog karcinoma. CDH1 u malignom metastatskom tkivu jetre je nezavisni prediktor ranog recidiva.

Background: There is limited data about expression of epithelial-mesenchymal transition (EMT) markers in patients with colorectal liver metastases (CRLM). Prognostic value of EMT markers in prediction of fast disease progression after curative-intent treatment is still not elucidated. Objective: To evaluate the expression and prognostic significance of CDH1, FN1 and VIM in patients with CRLM after curative-intent liver resection. Methods: Thirty patients with CRLM managed by curative-intent liver resection were included in this prospective pilot study. Blood samples, malignant metastatic tissue in the liver and surrounding non-tumor liver tissue were collected. Expression of CDH1, FN1 and VIM was analyzed by quantitative real-time polymerase chain reaction. Values were compared between groups created according to various clinico-pathological features. Results: The expression of CDH1 was similar in malignant metastatic tissue and non-tumor liver tissues, while FN1 and VIM expression was significantly lower in metastatic tissue (p=0.003 and p<0.001, respectively). Serum expression of CDH1 and VIM was detected in 66.7% and 93.3% of patients, respectively, while FN1 was not detected in any of the patients. The correlation of CDH1 and VIM expression between malignant metastatic tissue and serum was not statistically significant. Decreased CDH1 expression in malignant metastatic tissue and decreased VIM expression in serum was associated with early recurrence after surgical treatment of CRLM. CDH1 expression in malignant metastatic tissue was independent predictor of early recurrence one year after liver resection. Conclusions: Lower expression of CDH1 in malignant metastatic tissue and lower serum expression of VIM were found to be associated with early recurrence after liver resection for CRLM. CDH1 in malignant metastatic tissue is independect predictor of early recurrence.