Advancing Pan-cancer Gene Expression Survial Analysis by Inclusion of Non-coding RNA.

ABSTRACT

Non-coding RNAs occupy a significant fraction of the human genome. Their biological significance is backed up by a plethora of emerging evidence. One of the most robust approaches to demonstrate non-coding RNA's biological relevance is through their prognostic value. Using the rich gene expression data from The Cancer Genome Altas (TCGA), we designed Advanced Expression Survival Analysis (AESA), a web tool which provides several novel survival analysis approaches not offered by previous tools. In addition to the common single-gene approach, AESA computes the gene expression composite score of a set of genes for survival analysis and utilizes permutation test or cross-validation to assess the significance of log-rank statistic and the degree of over-fitting. AESA offers survival feature selection with post-selection inference and utilizes expanded TCGA clinical data including overall, disease-specific, disease-free, and progression-free survival information. Users can analyse either protein-coding or non-coding regions of the transcriptome. We demonstrated the effectiveness of AESA using several empirical examples. Our analyses showed that non-coding RNAs perform as well as messenger RNAs in predicting survival of cancer patients. These results reinforce the potential prognostic value of non-coding RNAs. AESA is developed as a module in the freely accessible analysis suite MutEx. Abbreviation ACC Adrenocortical Carcinoma (n = 92); BLCA Bladder Urothelial Carcinoma (n = 412); BRCA Breast Invasive Carcinoma (n = 1098); CESC Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (n = 307); CHOL Cholangiocarcinoma (n = 51); COAD Colon Adenocarcinoma (n = 461); DLBC Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (n = 58); ESCA Oesophageal Carcinoma (n = 185); GBM Glioblastoma Multiforme (n = 617); HNSC Head and Neck Squamous Cell Carcinoma (n = 528); KICH Kidney Chromophobe (n = 113); KIRC Kidney Renal Clear Cell Carcinoma (n = 537); KIRP Kidney Renal Papillary Cell Carcinoma (n = 291); LAML Acute Myeloid Leukaemia (n = 200); LGG Brain Lower Grade Glioma (n = 516); LIHC Liver Hepatocellular Carcinoma (n = 377); LUAD Lung Adenocarcinoma (n = 585); LUSC Lung Squamous Cell Carcinoma (n = 504); MESO Mesothelioma (n = 87); OV Ovarian Serous Cystadenocarcinoma (n = 608) PAAD Pancreatic Adenocarcinoma (n = 185); PCPG Pheochromocytoma and Paraganglioma (n = 179); PRAD Prostate Adenocarcinoma (n = 500); READ Rectum Adenocarcinoma (n = 172); SARC Sarcoma (n = 261); SKCM Skin Cutaneous Melanoma (n = 470); STAD Stomach Adenocarcinoma (n = 443); TGCT Testicular Germ Cell Tumours (n = 150); THCA Thyroid Carcinoma (n = 507) THYM Thymoma (n = 124); UCEC Uterine Corpus Endometrial Carcinoma (n = 560); UCS Uterine Carcinosarcoma (n = 57); UVM Uveal Melanoma (n = 80).