title: Robust transcriptional tumor signatures applicable to both formalin-fixed paraffin-embedded and fresh-frozen samples.
abstract: Formalin-fixed paraffin-embedded (FFPE) samples represent a valuable resource for clinical researches. However, FFPE samples are usually considered an unreliable source for gene expression analysis due to the partial RNA degradation. In this study, through comparing gene expression profiles between FFPE samples and paired fresh-frozen (FF) samples for three cancer types, we firstly showed that expression measurements of thousands of genes had at least two-fold change in FFPE samples compared with paired FF samples. Therefore, for a transcriptional signature based on risk scores summarized from the expression levels of the signature genes, the risk score thresholds trained from FFPE (or FF) samples could not be applied to FF (or FFPE) samples. On the other hand, we found that more than 90% of the relative expression orderings (REOs) of gene pairs in the FF samples were maintained in their paired FFPE samples and largely unaffected by the storage time. The result suggested that the REOs of gene pairs were highly robust against partial RNA degradation in FFPE samples. Finally, as a case study, we developed a REOs-based signature to distinguish liver cirrhosis from hepatocellular carcinoma (HCC) using FFPE samples. The signature was validated in four datasets of FFPE samples and eight datasets of FF samples. In conclusion, the valuable FFPE samples can be fully exploited to identify REOs-based diagnostic and prognostic signatures which could be robustly applicable to both FF samples and FFPE samples with degraded RNA.
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Rou
authors.initials: R
authors.lastname: Chen
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Qingzhou
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Guini
authors.initials: G
authors.lastname: Hong
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ao
authors.affiliation: Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D019295:Computational Biology; D030541:Databases, Genetic; D005404:Fixatives / Q000737:chemistry*; D005557:Formaldehyde / Q000737:chemistry*; D005615:Freezing; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D020871:RNA Stability; D012334:RNA, Neoplasm / Q000235:genetics*; D015203:Reproducibility of Results; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D005404:Fixatives; D012334:RNA, Neoplasm; D005557:Formaldehyde
keywords: RNA degradation; formalin-fixed paraffin-embedded samples; fresh-frozen samples; gene expression measurements; relative expression orderings