The significant reducing cost of next generation sequencing makes it possible to introduce Omics and bioinformatics study in cancer relative study. Cancer is a genetic disease, which is difficult to understand all the molecular network in the affected organisms. Transcriptomics sequencing and analysis are powerful tools to sequence the whole message RNA and provide a comprehensive expression profile for a given tissues at a time, they are widely applied in cancer researches. Here, we identified mitochondrial role in human lung cancer classification and prognosis and worked out the anti-cancer mechanism by comparing the expression differences of oncogenic insult experiments between cancer-resistant and cancer-suspectable species using comparative transcriptomics technology.
Human lung cancer is a very prevalent disease and mitochondria were speculated to be related to cancer development and classification. By integrating and analysing the publicly available transcriptome sequencing data, the human lung cancer subtypes and their different prognosis were determined based on the mtDNA expression profile. Two known longevity but naturally cancer-resistant subterranean rodents, including the naked mole-rat (short as NMR) and blind mole-rat (short as BMR) are receiving more and more attentions. To further understand the genes and pathways related to cancer resistant, a comprehensive oncogenic insult (using SV40LT and Ras oncogene) study in the fibroblast cells from cancer-resistant species (NMR, BMR, and Human) and cancer-susceptible species (Mouse) were performed. By analysing the transcriptome data driven from these experiments, NMR cells are found to be more antagonistic to oncogene-induced transcriptional changes, many pathways, including cell division, cell adhesion, extracellular matrix organization and metabolic process, remained stable or change to a less extent in NMR but significantly altered in cancer-suspectable mouse cells. Critical genes, such as Akt and Erk, in the PI3K and MAPK pathways were down-regulated specifically in the NMR cells which could partly explain its cancer-resistant and confirmed by the observation of tumorigenesis in NMR when overexpressing Ras. Taken together, these studies in this thesis reveal the power of transcriptome in cancer relative research and the output provides multiple new insights into the mitochondrial function in human lung cancer stratification and the underlying anti-cancer mechanisms in mammalian cancer-resistant species.