Identification and Clinical Validation of a Novel 4 Gene-Signature with Prognostic Utility in Colorectal Cancer

Ahluwalia, Pankaj; Mondal, Ashis; Bloomer, Chance; Fulzele, Sadanand; Jones, Kimya; Ananth, Sudha; Gahlay, Gagandeep Kaur; Heneidi, Saleh; Rojiani, Amyn M.; Kota, Vamsi; Kolhe, Ravindra

doi:10.3390/ijms20153818

Cited by 51 publications

(36 citation statements)

References 49 publications

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“…In brief, we screened 127 DEGs by comparing the gene expression profiles of primary tumors from metastatic patients with those from primary patients. Most previous studies focused on the differentially expressed regulators between tumor tissue and normal tissue (22)(23)(24). However, in the present study, we analyzed DEmiRNAs and DEGs between non-distant metastatic and distant metastatic COAD patients.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Lou

et al. 2020

Front. Oncol.

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Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosisrelated genes associated with distant metastasis and develop therapeutic strategies for COAD patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated. Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD. Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Lou

et al. 2020

Front. Oncol.

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“…Reviewing the previous literature on the prognosis of CRC, 4 gene signatures [ 28 ], 9 gene signatures [ 7 ], hypoxia-related signature [ 29 ], autophagy score signature [ 30 , 31 ], somatic mutation signatures [ 32 ], metabolism-related signature [ 33 ], chemokine/chemokine receptor signature [ 34 ], and immune-related signature [ 35 ] had been constructed to predict the OS of CRC patients. However, these bioinformatic analyses only predict the prognosis of CRC patients at the RNA level, and there are few studies on the protein prognostic signature.…”

Section: Discussionmentioning

confidence: 99%

Identification of 6 Hub Proteins and Protein Risk Signature of Colorectal Cancer

Yue

Liu

Zhu

et al. 2020

BioMed Research International

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Background. Colorectal cancer (CRC) is the second most common cause of cancer death in the United States and the third most common cancer globally. The incidence of CRC tends to be younger, and we urgently need a reliable prognostic assessment strategy. Methods. Protein expression profile and clinical information of 390 CRC patients/samples were downloaded from the TCPA and TCGA database, respectively. The Kaplan-Meier, Cox regression, and Pearson correlation analysis were applied in this study. Results. Based on the TCPA and TCGA database, we screened 6 hub proteins and first constructed protein risk signature, all of which were significantly associated with CRC patients’ overall survival (OS). The risk score was an independent prognostic factor and significantly related with the size of the tumor in situ ( T ). 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database. Next, 40 coexpressed proteins of 6 hub proteins were extracted from the TCPA database. In the protein-protein interaction (PPI) network, HER1, HER2, and CTNNB1 were at the center. Function enrichment analysis illustrated that 46 proteins were mainly involved in the EGFR (HER1) tyrosine kinase inhibitor resistance pathway. Conclusion. Studies indicated that 6 hub proteins might be considered as new targets for CRC therapies, and the protein risk signature can be used to predict the OS of CRC patients.

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“…Carcinoembryonic antigen (CEA) was a recommended prognostic marker in CRC for tumor diagnosis and monitoring response to therapy (Campos-da-Paz et al, 2018 ). Ahluwalia et al ( 2019 ) identified a novel 4-gene prognostic signature that had clinical utility in colorectal cancer. However, there are few clinical studies about biomarkers and gene pathways which have no risk of recurrence and tumor survival time.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Diagnostic and Prognostic Biomarkers for Colorectal Cancer Based on GEO and TCGA Databases

Wang

Guo

et al. 2021

Front. Genet.

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Colorectal cancer (CRC) is one of the most common neoplastic diseases worldwide. With a high recurrence rate among all cancers, treatment of CRC only improved a little over the last two decades. The mortality and morbidity rates can be significantly lessened by earlier diagnosis and prompt treatment. Available biomarkers are not sensitive enough for the diagnosis of CRC, whereas the standard diagnostic method, endoscopy, is an invasive test and expensive. Hence, seeking the diagnostic and prognostic biomarkers of CRC is urgent and challenging. With that order, we screened the overlapped differentially expressed genes (DEGs) of GEO (GSE110223, GSE110224, GSE113513) and TCGA datasets. Subsequent protein–protein interaction network analysis recognized the hub genes among these DEGs. Further functional analyses including Gene Ontology and KEGG pathway analysis and gene set enrichment analysis were processed to investigate the role of these genes and potential underlying mechanisms in CRC. Kaplan–Meier analysis and Cox hazard ratio analysis were carried out to clarify the diagnostic and prognostic role of these genes. In conclusion, our present study demonstrated that CCNA2, MAD2L1, DLGAP5, AURKA, and RRM2 are all potential diagnostic biomarkers for CRC and may also be potential treatment targets for clinical implication in the future.

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Identification and Clinical Validation of a Novel 4 Gene-Signature with Prognostic Utility in Colorectal Cancer

Cited by 51 publications

References 49 publications

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma

Identification of 6 Hub Proteins and Protein Risk Signature of Colorectal Cancer

Identification of Potential Diagnostic and Prognostic Biomarkers for Colorectal Cancer Based on GEO and TCGA Databases

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