Molecular characterization of colorectal cancer: A five-gene prognostic signature based on RNA-binding proteins

Liang, Qiankun; Du, Xiaojuan; Mao, Lanfang; Wang, Guopan

doi:10.4103/sjg.sjg_530_20

Cited by 5 publications

(4 citation statements)

References 64 publications

(72 reference statements)

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“…NAT10 and CSE1L have already been involved in COREAD ( Sillars-Hardebol et al, 2012 ; Tai et al, 2013 ; Zhang et al, 2014 ; Liu et al, 2016 ; 2019 ; Pimiento et al, 2016 ; Cao et al, 2020 ; Xu et al, 2020 ). NOP56 and RBM12 were already identified in COREAD by different data mining approaches ( Liang et al, 2021 ), validating our results. Additionally, to the best of our knowledge, no prior studies have associated FKBP1A and EMG1 with cancer before.…”

Section: Discussionsupporting

confidence: 89%

“…In COAD, we identified two RBPs (NAT10 and NOP56) having all four tumor-associated characteristics presented in this study. NAT10 has already been implicated in colorectal cancer in several studies ( Zhang et al, 2014 ; Liu et al, 2016 ; 2019 ; Cao et al, 2020 ), while NOP56 has been found differentially expressed in COREAD by a different data mining approach ( Liang et al, 2021 ). Also, we were able to retrieve two other RBPs (RBM12 and FKBP1A) that were not essential for tumor cell survival, but they could be implicated in any other hallmark of cancer.…”

Section: Resultsmentioning

confidence: 99%

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Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

García-Cárdenas,

Armendáriz-Castillo,

García-Cárdenas

et al. 2023

Front. Cell Dev. Biol.

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Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

García-Cárdenas,

Armendáriz-Castillo,

García-Cárdenas

et al. 2023

Front. Cell Dev. Biol.

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“…Kaplan–Meier survival plots, receiver operating characteristic (ROC), C-index and DCA curves, visualized by R package“survival”, “timeROC”,“ggDCA” and “survminer”, were used to evaluate prognostic value of risk model in colon cancer. The constructed model in this study was also compared with known models in predicting the prognosis of colon patients ( Huang et al, 2018 ; Li et al, 2021 ; Liang et al, 2021 ). Univariate and multifactor analyses were performed to determine the independent prognostic value of the risk model.…”

Section: Materials Methodsmentioning

confidence: 99%

m7G-Related DNA Damage Repair Genes are Potential Biomarkers for Predicting Prognosis and Immunotherapy Effectiveness in Colon Cancer Patients

Chen

Dong²,

Li³

et al. 2022

Front. Genet.

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Objective: m7G is a post-transcriptional modification modality, however, limited research has been conducted on its role in colon cancer. DNA damage repair (DDR) is an important factor that contributes to colon cancer development, growth and chemoresistance. This study aimed to explore whether m7G-related DNA damage repair genes may be used as biomarkers to predict the prognosis of colon cancer patients.Methods: We use non-negative matrix factorization (NMF) to type CRC patients into. Risk models were constructed using different expression genes in two clusters. We assessed the reliability of risk models with DCA curves, and a Nomogram. Meanwhile, The receiver operating characteristic and C-index curves were used to compare the predictive significance of the constructed risk models with other studies. In additional, we examined the significance of risk models on patients’ immunity microenvironment and response to immune therapy. Finally, we used a series of cellular experiments to validate the effect of model genes on the malignant progression of CRC cells.Results: Twenty-eight m7G genes were obtained from the GSEA database. Multivariate Cox and LASSO Cox regression analysis was performed and eleven m7G-related DDR genes were identified for constructing the risk model. Survival and stage of CRC patients were worser in the high-risk group than in the low-risk group for both the training and test sets. Additionally, the different immune microenvironment status of patients in the high- and low-risk groups, suggesting that patients in the low-risk group may be more sensitive to immunotherapy, particularly immune checkpoint inhibitors. Finally, we found that depletion of ATP2A1, one of the risk genes in our model, influence the biologic behaviour of CRC cells significantly.Conclusion: The m7G-related DDR genes can be used as important markers for predicting patient prognosis and immunotherapy response. Our data suggest that ATP2A1 may promote the proliferation of colon cancer cells. These findings may provide new therapeutic targets for the treatment of colon cancer.

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“…Likewise, IGF2BP3 is involved in constructing prognostic models of colorectal cancer. Liang et al screened and identified five RNA-binding protein-related prognostic signatures from TCGA (IGF2BP3, PABPC1L, PPARGC1A, PTRH1, and TDRD7) [85]. Busuioc et al found that the epithelial-mesenchymal transition gene signature can predict the overall survival rate of colon adenocarcinoma patients (NOX4, IGF2BP3, DACT3, EEF1A2, BMP5, GCNT2, and SFRP1) [86].…”

Section: Colorectal Cancermentioning

confidence: 99%

Targeting IGF2BP3 in Cancer

Liu

Chen

et al. 2023

IJMS

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RNA-binding proteins (RBPs) can regulate multiple pathways by binding to RNAs, playing a variety of functions, such as localization, stability, and immunity. In recent years, with the development of technology, researchers have discovered that RBPs play a key role in the N6-methyladenosine (m6A) modification process. M6A methylation is the most abundant form of RNA modification in eukaryotes, which is defined as methylation on the sixth N atom of adenine in RNA. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is one of the components of m6A binding proteins, which plays an important role in decoding m6A marks and performing various biological functions. IGF2BP3 is abnormally expressed in many human cancers, often associated with poor prognosis. Here, we summarize the physiological role of IGF2BP3 in organisms and describe its role and mechanism in tumors. These data suggest that IGF2BP3 may be a valuable therapeutic target and prognostic marker in the future.

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Molecular characterization of colorectal cancer: A five-gene prognostic signature based on RNA-binding proteins

Cited by 5 publications

References 64 publications

Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

m7G-Related DNA Damage Repair Genes are Potential Biomarkers for Predicting Prognosis and Immunotherapy Effectiveness in Colon Cancer Patients

Targeting IGF2BP3 in Cancer

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