Details

Autor(en) / Beteiligte

• Odenthal, Margarete
• Hee, Julia
• Gockel, Ines
• Sisic, Leila
• Schmitz, Jolly
• Stoecklein, Nikolas H.
• Driemel, Christiane
• Möhlendick, Birte
• Schmidt, Thomas
• Knoefel, Wolfram T.
• Lang, Hauke
• Büttner, Reinhard
• Ott, Katja
• Vallböhmer, Daniel

Titel

Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction

Ist Teil von

• International journal of cancer, 2015-07, Vol.137 (1), p.230-237

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Wiley Online Library Database Model

Beschreibungen/Notizen

• Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis of locally advanced adenocarcinomas of the gastroesophageal junction. This study aimed to asses if serum microRNA profiles are useable as response indicators in this therapeutic setting. Fifty patients with locally advanced adenocarcinomas of the gastroesophageal junction were included in the study. All patients received neoadjuvant therapy and subsequently underwent surgical resection. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10% vital residual tumor cells. Circulating RNA was isolated from pretherapeutic/post‐neoadjuvant blood serum samples. RNA from nine patients was applied to PCR microarray analyses Based on these findings possible predictive miRNA markers were validated by quantitative RT‐PCR analyses. Depending on the histomorphologic regression, a differential serum microRNA profile was identified by microarray analyses. Based on the divergent miRNA pattern, miR‐21, miR‐192, miR‐222, miR‐302c, miR‐381 and miR‐549 were selected for further validation. During neoadjuvant therapy, there was a significant increase of miR 222 and miR‐549. Although on an expanded patient cohort, the six microRNAs could not be validated as markers for therapy response, there was a significant correlation between a high miR‐192 and miR‐222 expression with a high T‐category as well as miR‐302c and miR‐222 expression significantly correlated with overall survival. Comprehensive miRNA profiling showed a differential microRNA expression pattern depending on the histomorphologic regression in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction. Moreover, using single RT‐PCR analyses a prognostic impact of miR‐222 and miR‐302c was detected. What's New? Advanced esophageal cancer is increasingly treated through combinations of therapeutic approaches, including neoadjuvant therapies. But only certain subsets of patients benefit from multimodal strategies, which has created a need for tools capable of predicting patient response. Potential, non‐invasive predictive markers include miRNAs. From microarray analyses, the authors of the present study were able to identify differential serum miRNA profiles among patients with advanced esophageal adenocarcinoma who received neoadjuvant therapy. Of six miRNAs selected for validation, two were found to be of potential prognostic significance. The findings warrant further investigation of the markers in studies with larger patient populations.