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5-year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of this study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs favorable prognosis) were selected. RNA-sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to disease-free survival (DFS), 108 differentially expressed genes (104/4 up/down-regulated in the unfavorable prognosis group) were identified. Among 104 up-regulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as: pseudogenes (n=17), uncharacterized non-coding RNA (n=10), immune response genes (n=4), miRNA (n=1), cancer-related genes (n=14), cancer-unrelated genes (n=16). Three out of 4 down-regulated genes were cancer-related. Mutational status (i.e. RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p=0.018 and p=0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: International journal of cancer
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Methods to determine in patients the nature of a disease or disorder at its early stage of progression. Generally, early diagnosis improves PROGNOSIS and TREATMENT OUTCOME.
A factor associated with the well-being of living organisms that is used as a measure of environmental change and or influence. For example, aldehyde dehydrogenase expression in earthworm tissue is used as an indication of heavy metal pollution in soils. Distinguish from BIOMARKERS.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or BODY FLUIDS. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including HORMONES; ANTIGENS; amino and NUCLEIC ACIDS; ENZYMES; POLYAMINES; and specific CELL MEMBRANE PROTEINS and LIPIDS.
The stage in the first meiotic prophase, following ZYGOTENE STAGE, when CROSSING OVER between homologous CHROMOSOMES begins.
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