Pan-Cancer Analyses Reveal Long Intergenic Non-Coding RNAs Relevant to Tumor Diagnosis, Subtyping and Prognosis.
Long intergenic noncoding RNAs (lincRNAs) are a relatively new class of non-coding RNAs that have the potential as cancer biomarkers. To seek a panel of lincRNAs as pan-cancer biomarkers, we have analyzed transcriptomes from over 3300 cancer samples with clinical information. Compared to mRNA, lincRNAs exhibit significantly higher tissue specificities that are then diminished in cancer tissues. Moreover, lincRNA clustering results accurately classify tumor subtypes. Using RNA-Seq data from thousands of paired tumor and adjacent normal samples in The Cancer Genome Atlas (TCGA), we identify six lincRNAs as potential pan-cancer diagnostic biomarkers (PCAN-1 to PCAN-6). These lincRNAs are robustly validated using cancer samples from four independent RNA-Seq data sets, and are verified by qPCR in both primary breast cancers and MCF-7 cell line. Interestingly, the expression levels of these six lincRNAs are also associated with prognosis in various cancers. We further experimentally explored the growth and migration dependence of breast and colon cancer cell lines on two of the identified lncRNAs. In summary, our study highlights the emerging role of lincRNAs as potentially powerful and biologically functional pan-cancer biomarkers and represents a significant leap forward in understanding the biological and clinical functions of lincRNAs in cancers.
Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Travers
T
Ching
Genomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
Karolina
K
Peplowska
Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Sijia
S
Huang
Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Xun
X
Zhu
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Yi
Y
Shen
Genomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
Janos
J
Molnar
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
Herbert
H
Yu
Genomics Shared Resource, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
Maarit
M
Tiirikainen
Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA.
Ben
B
Fogelgren
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
Rong
R
Fan
Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA. Electronic address: lgarmire@cc.hawaii.edu.
Lana X
LX
Garmire
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D009928:Organ Specificity; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*
D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding
LincRNA; RNASeq; biomarkers; lncRNA; pan-cancer