Dataset Information

Comprehensive transcriptome analysis of colorectal cancer risk of hyperglycemia in humans.

ABSTRACT:

Background

Epidemiological studies have found that hyperglycemia, is an independent risk factor for colorectal cancer (CRC), increasing colon cancer incidence and affecting the recurrence, metastasis, and prognosis in colon cancer patients. However, the intercorrelation between hyperglycemia and CRC risk is still unknown, In the present study, we sought to determine whether gene markers, which act in CRC with hyperglycemia, are silenced in CRC without hyperglycemia.

Methods

In order to characterize the mechanism of functional genes associated with CRC with hyperglycemia, A total 24 CRC and matched controls were sequenced. Through bioinformatics analysis includes differential expression analysis, functional enrichment, new isoform prediction and alternative splicing event identification to found biomarker genes related to CRC development.

Results

CRC patients with hyperglycemia were compared with patients without hyperglycemia, and we found that 21 genes were upregulated and 27 were downregulated. Further study showed that these genes are possibly of key genes involved in CRC development with hyperglycemia, such as mannan-binding lectin-associated serine protease 3 (MASP3), which has an immunological role in the activation of the complement system. Based on our comprehensive analysis, a cis-regulatory network for hyperglycemic CRC was reconstructed.

Conclusions

Protein-protein interactions revealed the mechanisms of molecules involved in the interaction of hyperglycemia and cancer development. Our results provide further information on the metabolic pathway interaction with cancer pathways and elucidated the mechanisms of hyperglycemic factors function in cancer development from a transcriptomic perspective.

SUBMITTER: Feng W

PROVIDER: S-EPMC8107623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.