 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 03, 2020 |
| Title |
RNA sequencing reveals PNN as a predictive biomarker of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Five-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 our 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/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancer-related genes (n = 14) and cancer-unrelated genes (n = 16). Three out of four 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.
|
| |
|
| Overall design |
Two extreme cohort study according to chemotherapy outcome
|
| |
|
| Contributor(s) |
Mini E, Lapucci A, Perrone G, D’Aurizio R, Napoli C, Brugia M, Landini I, Tassi R, Picariello L, Simi L, Mancini I, Messerini L, Magi A, Pinzani P, Mazzei T, Tonelli F, Nobili S |
| Citation(s) |
30973654 |
| Submission date |
Nov 07, 2018 |
| Last update date |
May 03, 2020 |
| Contact name |
Stefania Nobili |
| E-mail(s) |
stefania.nobili@unifi.it
|
| Organization name |
University of Florence
|
| Department |
Health Sciences
|
| Street address |
viale Pieraccini 6
|
| City |
Firenze |
| ZIP/Postal code |
50139 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
|
| Samples (24)
|
| GSM3462547 |
stage III CRC patient_favorable_IonXpress_001 |
| GSM3462548 |
stage III CRC patient_favorable_IonXpress_002 |
| GSM3462549 |
stage III CRC patient_favorable_IonXpress_003 |
| GSM3462550 |
stage III CRC patient_unfavorable_IonXpress_004 |
| GSM3462551 |
stage III CRC patient_favorable_IonXpress_005 |
| GSM3462552 |
stage III CRC patient_unfavorable_IonXpress_006 |
| GSM3462553 |
stage III CRC patient_favorable_IonXpress_007 |
| GSM3462554 |
stage III CRC patient_favorable_IonXpress_008 |
| GSM3462555 |
stage III CRC patient_unfavorable_IonXpress_009 |
| GSM3462556 |
stage III CRC patient_favorable_IonXpress_010 |
| GSM3462557 |
stage III CRC patient_favorable_IonXpress_011 |
| GSM3462558 |
stage III CRC patient_unfavorable_IonXpress_012 |
| GSM3462559 |
stage III CRC patient_unfavorable_IonXpress_013 |
| GSM3462560 |
stage III CRC patient_unfavorable_IonXpress_014 |
| GSM3462561 |
stage III CRC patient_unfavorable_IonXpress_015 |
| GSM3462562 |
stage III CRC patient_favorable_IonXpress_016 |
| GSM3462563 |
stage III CRC patient_unfavorable_IonXpress_017 |
| GSM3462564 |
stage III CRC patient_favorable_IonXpress_018 |
| GSM3462565 |
stage III CRC patient_unfavorable_IonXpress_019 |
| GSM3462566 |
stage III CRC patient_unfavorable_IonXpress_020 |
| GSM3462567 |
stage III CRC patient_favorable_IonXpress_021 |
| GSM3462568 |
stage III CRC patient_unfavorable_IonXpress_022 |
| GSM3462569 |
stage III CRC patient_unfavorable_IonXpress_023 |
| GSM3462570 |
stage III CRC patient_favorable_IonXpress_024 |
|
| Relations |
| BioProject |
PRJNA504394 |
| SRA |
SRP168011 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122246_AST.bcmatrix.txt.gz |
769.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...