Proteogenomic Study beyond Chromosome 9: New Insight into Expressed Variant Proteome and Transcriptome in Human Lung Adenocarcinoma Tissues

This
is a report of a human proteome project (HPP) related to chromosome
9 (Chr 9). To reveal missing proteins and undiscovered features in
proteogenomes, both LC–MS/MS analysis and next-generation RNA
sequencing (RNA-seq)-based identification and characterization were
conducted on five pairs of lung adenocarcinoma tumors and adjacent
nontumor tissues. Before our previous Chromosome-Centric Human Proteome
Project (C-HPP) special issue, there were 170 remaining missing proteins
on Chr 9 (neXtProt 2013.09.26 rel.); 133 remain at present (neXtProt
2015.04.28 rel.). In the proteomics study, we found two missing protein
candidates that require follow-up work and one unrevealed protein
across all chromosomes. RNA-seq analysis detected RNA expression for
four nonsynonymous (NS) single nucleotide polymorphisms (SNPs) (in
CDH17, HIST1H1T, SAPCD2, and ZNF695) and three synonymous SNPs (in
CDH17, CST1, and HNF1A) in all five tumor tissues but not in any of
the adjacent normal tissues. By constructing a cancer patient sample-specific
protein database based on individual RNA-seq data and by searching
the proteomics data from the same sample, we identified four missense
mutations in four genes (LTF, HDLBP, TF, and HBD). Two of these mutations
were found in tumor samples but not in paired normal tissues. In summary,
our proteogenomic study of human primary lung tumor tissues detected
additional and revealed novel missense mutations and synonymous SNP
signatures, some of which are specific to lung cancers. Data from
mass spectrometry have been deposited in the ProteomeXchange with
the identifier PXD002523.