RGD Reference Report - Integrative Proteo-Genomic Analysis for Recurrent Survival Prognosis in Colon Adenocarcinoma. - Rat Genome Database

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Integrative Proteo-Genomic Analysis for Recurrent Survival Prognosis in Colon Adenocarcinoma.

Authors: Ai, FeiYan  Wang, Wenhao  Liu, Shaojun  Zhang, Decai  Yang, Zhenyu  Liu, Fen 
Citation: Ai F, etal., Front Oncol. 2022 Jun 30;12:871568. doi: 10.3389/fonc.2022.871568. eCollection 2022.
RGD ID: 153352327
Pubmed: PMID:35847888   (View Abstract at PubMed)
PMCID: PMC9281446   (View Article at PubMed Central)
DOI: DOI:10.3389/fonc.2022.871568   (Journal Full-text)


Background: The survival prognosis is the hallmark of cancer progression. Here, we aimed to develop a recurrence-related gene signature to predict the prognosis of colon adenocarcinoma (COAD).
Methods: The proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and genomic data from the cancer genomic maps [The Cancer Genome Atlas (TCGA)] dataset were analyzed to identify co-differentially expressed genes (cDEGs) between recurrence samples and non-recurrence samples in COAD using limma package. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. Univariate and multivariate Cox regressions were applied to identify the independent prognostic feature cDEGs and establish the signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index), and calibration curve. The area under the receiver operating characteristic (ROC) curve (AUROC) and a nomogram were calculated to assess the predictive accuracy. GSE17538 and GSE39582 were used for external validation. Quantitative real-time PCR and Western blot analysis were carried out to validate our findings.
Results: We identified 86 cDEGs in recurrence samples compared with non-recurrence samples. These genes were primarily enriched in the regulation of carbon metabolic process, fructose and mannose metabolism, and extracellular exosome. Then, an eight-gene-based signature (CA12, HBB, NCF1, KBTBD11, MMAA, DMBT1, AHNAK2, and FBLN2) was developed to separate patients into high- and low-risk groups. Patients in the low-risk group had significantly better prognosis than those in the high-risk group. Four prognostic clinical features, including pathological M, N, T, and RS model status, were screened for building the nomogram survival model. The PCR and Western blot analysis results suggested that CA12 and AHNAK2 were significantly upregulated, while MMAA and DMBT1 were downregulated in the tumor sample compared with adjacent tissues, and in non-recurrent samples compared with non-recurrent samples in COAD.
Conclusion: These identified recurrence-related gene signatures might provide an effective prognostic predictor and promising therapeutic targets for COAD patients.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CA12Humancolon adenocarcinoma disease_progressionIEP  RGD 
Car12Ratcolon adenocarcinoma disease_progressionISOCA12 (Homo sapiens) RGD 
Car12Mousecolon adenocarcinoma disease_progressionISOCA12 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Car12  (carbonic anhydrase 12)

Genes (Mus musculus)
Car12  (carbonic anhydrase 12)

Genes (Homo sapiens)
CA12  (carbonic anhydrase 12)


Additional Information