RESUMO
Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more H19, HULC and HOTTIP transcripts in comparison to CRC patients. Correlation analysis between lncRNAs and clinical data revealed a statistical significance between low levels of exosomal HOTTIP and poor overall survival. This was confirmed by multivariate analysis that HOTTIP is an independent prognostic marker for overall survival (HR: 4.5, CI: 1.69-11.98, p = 0.0027). Here, HOTTIP poses to be a valid biomarker for patients with a CRC to predict post-surgical survival time.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Exossomos/metabolismo , Exossomos/ultraestrutura , Perfilação da Expressão Gênica , Humanos , Biópsia Líquida , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
Biomarkers may help predict the efficacy of neoadjuvant chemoradiation in patients with rectal cancer. We hypothesized that the expression of topoisomerase I (Topo I) and thymidylate synthase (TS) may help predict the treatment response in patients undergoing irinotecan and capecitabine-based chemoradiation. Patients with rectal cancer (cT3/4Nx or Tx/N+) received neoadjuvant chemoradiotherapy within clinical studies with irinotecan and capecitabine. Samples of normal and tumour tissues were collected before the start of the treatment and during surgical resection. Topo I and TS were measured using real-time PCR. The results of gene expression levels were compared between responders (defined as ypT0-2 ypN0) and nonresponders (ypT3-4 or ypN1/2). A total of 38 patients were analysed, 18 of them were responders. The biopsies of the untreated tumour tissue of responding patients showed a significant higher expression of Topo I compared with nonresponding patients (P = 0.015). Normal tissue did not show this difference (P = 0.126). During chemoradiation, the Topo I expression in tumour tissue of responders decreased significantly. TS did not show any differences between responders and nonresponders before treatment, but a significant decrease in the tumour tissue of responders was noted at the end of the treatment. Our data suggest that Topo I expression in rectal tumour mucosa might serve as a predictor of response to the neoadjuvant irinotecan-based chemoradiation, and hence might be a factor contributing to the development of individualized treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , DNA Topoisomerases Tipo I/biossíntese , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Humanos , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Irinotecano , Terapia Neoadjuvante/métodos , Invasividade Neoplásica , Estudos Prospectivos , Neoplasias Retais/enzimologia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Timidilato Sintase/biossínteseRESUMO
PURPOSE: Deviant expression of platelet-derived growth factor receptor-beta (PDGFRbeta) and c-kit was shown in patients with colorectal cancer. In the present study, mRNA expression of PDGFRbeta and c-kit in 33 patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy with cetuximab/capecitabine/irinotecan in correlation with the tumor regression rate was investigated. METHODS AND MATERIALS: Pretherapeutic biopsy cores and tumor material from the resected specimens were collected in parallel with normal rectal mucosa. The expression levels of PDGFRbeta and c-kit were measured by quantitative polymerase chain reaction. Tumors were classified as good responders (tumor regression grade [TRG], 2-3) or poor responders (TRG, 0-1). RESULTS: The TRG evaluation of the resected specimen was TRG 0-1 in 11 and TRG 2-3 in 22. The median normalized ratios in the pretreatment mucosa vs. tumor biopsy cores was as follows: PDGFRbeta ratio of 15.2 vs. 49.5 (p <0.0001) and c-kit ratio of 0.94 vs. 0.67 (p = 0.014). The same tendency was observed for the median PDGFRbeta ratios after chemoradiotherapy completion: 34.2 vs. 170.0 (p <0.0001). The PDGFRbeta and c-kit mRNA expression values in the pretreatment tumor biopsy cores were lower than the values in the resected specimens: PDGFRbeta ratio 49.5 vs. 170.0 (p = 0.0002) and c-kit ratio 0.67 vs. 1.1 (p = 0.0003). Nevertheless, no correlation was seen between the pretherapeutic PDGFRbeta and c-kit mRNA expression and the pathologic regression rate. CONCLUSION: Cetuximab-based chemoradiotherapy increased PDGFRbeta levels even further compared with the pretreatment samples and deserves further investigation.
