Dataset Information

Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues.

ABSTRACT: Cancer prevails in various gastrointestinal (GI) organs, such as esophagus, stomach, and colon. However, the small intestine has an extremely low cancer risk. It is interesting to investigate the molecular cues that could explain the significant difference in cancer incidence rates among different GI tissues. Using several large-scale normal and cancer tissue genomics datasets, we compared the gene expression profiling between small intestine and other GI tissues and between GI cancers and normal tissues. We identified 17 tumor suppressor genes (TSGs) which showed significantly higher expression levels in small intestine than in other GI tissues and significantly lower expression levels in GI cancers than in normal tissues. These TSGs were mainly involved in metabolism, immune, and cell growth signaling-associated pathways. Many TSGs had a positive expression correlation with survival prognosis in various cancers, confirming their tumor suppressive function. We demonstrated that the downregulation of many TSGs was associated with their hypermethylation in cancer. Moreover, we showed that the expression of many TSGs inversely correlated with tumor purity and positively correlated with antitumor immune response in various cancers, suggesting that these TSGs may exert their tumor suppressive function by promoting antitumor immunity. Furthermore, we identified a transcriptional regulatory network of the TSGs and their master transcriptional regulators (MTRs). Many of MTRs have been recognized as tumor suppressors, such as HNF4A, ZBTB7A, p53, and RUNX3. The TSGs could provide new molecular cues associated with tumorigenesis and tumor development and have potential clinical implications for cancer diagnosis, prognosis, and treatment.

SUBMITTER: Sun Q

PROVIDER: S-EPMC7396062 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues.

Sun Qingrong Q Uddin Md Nazim MN Li Mengyuan M Wang Xiaosheng X Lai Maode M

Journal of oncology 20200722

Cancer prevails in various gastrointestinal (GI) organs, such as esophagus, stomach, and colon. However, the small intestine has an extremely low cancer risk. It is interesting to investigate the molecular cues that could explain the significant difference in cancer incidence rates among different GI tissues. Using several large-scale normal and cancer tissue genomics datasets, we compared the gene expression profiling between small intestine and other GI tissues and between GI cancers and norma ...[more]

PMID: 32774369

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Project description:The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their concentrations / profiles in normal and tumor tissues of human lung, breast and liver. These critical elements appeared to be respectively five to ten times more abundant in human lung and breast tumor than in their respective normal tissues. In contrast Ba, Cr, Cu, Fe, Zn, concentrations were shown to be lower in liver tumors than in normal liver tissues, and that Ca and Na appeared to be higher in human liver tumors than in normal liver tissues. Data analysis showed significant variations in elemental concentrations and profiles consistent with the hypothesis. It is concluded that metal / elemental homeostasis is essential for normal tissue function and that elemental variations and distributions are tissue specific as well as carcinoma specific. These results are promising and warrant further studies to confirm / exploit the possibility of manipulating elemental distribution and content as means for diagnosing / utility as therapeutic modalities in chronic human disease as well as cancer management.

Dataset Information

Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues.

Publications

Computational Identification of Tumor Suppressor Genes Based on Gene Expression Profiles in Normal and Cancerous Gastrointestinal Tissues.

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