Validation of a gene signature in histologically normal surgical margins predictive of oral squamous cell carcinoma recurrence
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PROVIDER: PRJNA428353 | ENA |
REPOSITORIES: ENA
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Project description:Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients.
2011-08-03 | GSE31056 | GEO
Project description:Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients. This was a case-only design involving a training set of 23 tumors and 73 margins from 24 patients with squamous cell carcinoma of the tongue.
2011-08-02 | E-GEOD-31056 | biostudies-arrayexpress
Project description:The aim of this study is to provide an extended, retrospective validation of a previously described 4-gene signature (MMP1, COL4A1, P4HA2, and THBS2) predictive of oral carcinoma recurrence. We assessed an independent cohort including 245 histologically normal surgical margins from 62 patients with OSCC. Gene expression was determined using a color-coded probe assay for quantitative gene expression analysis. All margins and tumor blocks were cut (4-5µm tick) and stained with Hematoxylin-Eosin and tissues were subjected to needle microdissection using the stereo microscope Leica EZ4 (Leica Microsystems, Wetzlar, Germany) before RNA extraction, in order to isolate pure tumor or normal cell populations. RNA from FFPE samples was isolated using the RecoverAll Total Nucleic Acid Isolation kit (Ambion/Life Technologies, Carlsbad, CA, USA), following our previously reported protocol with modifications to improve RNA yield [PMID:23835716]. RNA was stored at -80ºC until RNA extraction and gene expression validation. In addition, tumor tissues from the same patients were collected for further analysis (not in scope of the presented study). Probes were designed for the 4-gene signature (MMP1, COL4A1, P4HA2 and THBS2) and contained one capture probe linked to biotin and one reporter probe attached to a color-coded molecular tag for each gene sequence, according to the nCounterTM code-set design. RNA samples were randomized using a numerical ID and were then subjected to NanoString nCounterTM analysis by the Princess Margaret Genomics Centre (https://www.pmgenomics.ca), Toronto, ON, Canada. Patient samples were analyzed in two batches consisting of 125 and 152 margins tissue samples. The detailed protocol for mRNA transcript quantification analysis, including sample preparation, hybridization, detection and scanning followed the manufacturer’s recommendations and was described in [PMID: 21549012]. We used 400 ng of total RNA isolated from FFPE tissues for detection of probe signals. Raw data were analyzed using the nCounterTM digital analyzer software (http://www.nanostring.com/support/ncounter/) and gene expression levels were subjected to further bioinformatic and statistical analyses.
2020-02-07 | GSE108712 | GEO
Project description:Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC may aid in identifying a gene signature predictive of recurrence.We used a meta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets, in addition to our microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients.We identified 138 significantly over-expressed genes (> 2-fold, false discovery rate of 0.01) in OSCC. By penalized likelihood Cox regression, we identified a 4-gene signature with prognostic value for recurrence in our training set. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Over-expression of this 4-gene signature in histologically normal margins was associated with recurrence in our training cohort (p = 0.0003, logrank test) and in our independent validation cohort (p = 0.04, HR = 6.8, logrank test).Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. Our findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence.
| S-EPMC3198722 | biostudies-literature
Project description:A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence
| PRJNA144853 | ENA
Project description:Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients. This was a case-only design involving a training set of 23 tumors and 73 margins from 24 patients with squamous cell carcinoma of the tongue.
| S-ECPF-GEOD-31056 | biostudies-other
Project description:The purpose of this study was to provide molecular evidence that surgical margin definition using narrow band imaging (NBI) resulted in more complete OSCC excision that conventional while light (WL) imaging. Samples were taken prospectively from 18 patients undergoing surgical resection for intraoral SCC (excluding lip, pharynx and hypopharynx). Biopsies were taken from the tumour and from 5mm beyond each of the abnormal tissue margins defined by WL and NBI. Transcriptional profiling was performed by microarray.
2018-01-17 | E-MTAB-5933 | biostudies-arrayexpress
Project description:The purpose of this study was to provide molecular evidence that surgical margin definition using narrow band imaging (NBI) resulted in more complete OSCC excision that conventional while light (WL) imaging. Samples were taken prospectively from 18 patients undergoing surgical resection for intraoral SCC (excluding lip, pharynx and hypopharynx). Biopsies were taken from the tumour and from 5mm beyond each of the abnormal tissue margins defined by WL and NBI. MicroRNA profiling was performed by microarray.
2018-02-09 | E-MTAB-6470 | biostudies-arrayexpress
Project description:211 FFPE NSLC surgical samples were used to generate recurrence prediction models
2018-02-13 | GSE90623 | GEO
Project description:Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch's t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring.
| S-EPMC6997450 | biostudies-literature