The clinical relevance of gene expression based prognostic signatures in colorectal cancer

Ahluwalia, Pankaj; Kolhe, Ravindra; Gahlay, Gagandeep Kaur

doi:10.1016/j.bbcan.2021.188513

Cited by 61 publications

(55 citation statements)

References 124 publications

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“…It is not surprising that current individual gene biomarkers often fail to predict cancer prognosis accurately because a gene can hardly capture the distinct molecular heterogeneity of cancer. This challenge has spurred the development of multiple gene signatures predictive of outcomes in a broad spectrum of cancer [ 20 , 37 ]. Gene expression profile-based prognostic risk scores have recently emerged as promising biomarkers with substantial clinical values.…”

Section: Discussionmentioning

confidence: 99%

UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

Zhu

Liu

et al. 2021

J Transl Med

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Background Ubiquitin-conjugating enzyme E2T (UBE2T) acts as an oncogene in various types of cancer. However, the mechanisms behind its oncogenic role remain unclear in lung cancer. This study aims to explore the function and clinical relevance of UBE2T in lung cancer. Methods Lentiviral vectors were used to mediate UBE2T depletion or overexpress UBE2T in lung cancer cells. CCK8 analysis and western blotting were performed to investigate the effects of UBE2T on proliferation, autophagy, and relevant signaling pathways. To exploit the clinical significance of UBE2T, we performed immunohistochemistry staining with an anti-UBE2T antibody on 131 NSCLC samples. Moreover, we downloaded the human lung adenocarcinoma (LUAD) dataset from The Cancer Atlas Project (TCGA). Lasso Cox regression model was adopted to establish a prognostic model with UBE2T-correlated autophagy genes. Results We found that UBE2T stimulated proliferation and autophagy, and silencing this gene abolished autophagy in lung cancer cells. As suggested by Gene set enrichment analysis, we observed that UBE2T downregulated p53 levels in A549 cells and vice versa. Blockade of p53 counteracted the inhibitory effects of UBE2T depletion on autophagy. Meanwhile, the AMPK/mTOR signaling pathway was activated during UBE2T-mediated autophagy, suggesting that UBE2T promotes autophagy via the p53/AMPK/mTOR pathway. Interestingly, UBE2T overexpression increased cisplatin-trigged autophagy and led to cisplatin resistance of A549 cells, whereas inhibiting autophagy reversed drug resistance. However, no association was observed between UEB2T and overall survival in a population of 131 resectable NSCLC patients. Therefore, we developed and validated a multiple gene signature by considering UBE2T and its relevance in autophagy in lung cancer. The risk score derived from the prognostic signature significantly stratified LUAD patients into low- and high-risk groups with different overall survival. The risk score might independently predict prognosis. Interestingly, nomogram and decision curve analysis demonstrated that the signature’s prognostic accuracy culminated while combined with clinical features. Finally, the risk score showed great potential in predicting clinical chemosensitivity. Conclusions We found that UBE2T upregulates autophagy in NSCLC cells by activating the p53/AMPK/mTOR signaling pathway. The clinical predicting ability of UBE2T in LUAD can be improved by considering the autophagy-regulatory role of UBE2T.

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Section: Discussionmentioning

confidence: 99%

UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

Zhu

Liu

et al. 2021

J Transl Med

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“…A great effort has been done in order to identify patients with unfavourable prognosis that may benefit from adjuvant therapy. From the classical TNM staging system [6], several attempts to improve cancer classification have been proposed [7][8][9][10]. However, these methods have mainly focused on 'omics' and massive approaches that mask intra-tumour and inter-patient heterogeneity and involve high costs, avoiding large-scale clinical application [11].…”

Section: Introductionmentioning

confidence: 99%

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

et al. 2021

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Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.

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“…As the disease tends to show symptoms only at an advanced stage, multiple diagnostic strategies, including biopsy, laboratory examinations, and colonoscopy that aim for early detection and mortality reduction, are being implemented. In recent years, owing to evolving sequencing technologies, the models using molecular biomarkers to diagnose at an early stage and evaluate the survival prognosis in CRC patients have reduced CRC mortality rate ( Ahluwalia et al, 2021 ). However, on account of sampling bias and technical batch effects, the practical applicability of these models remains limited.…”

Section: Discussionmentioning

confidence: 99%

Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model

Zhang

Zhao

et al. 2021

Front. Genet.

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BackgroundAccumulating evidence has demonstrated that immune-related long non-coding ribonucleic acids (irlncRNAs) can be used as prognostic indicators of overall survival (OS) in patients with colorectal cancer (CRC). Our aim in this research, therefore, was to construct a risk model using irlncRNA pairs with no requirement for a specific expression level, in hope of reliably predicting the prognosis and immune landscape of CRC patients.MethodsClinical and transcriptome profiling data of CRC patients downloaded from the Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed (DE) irlncRNAs. The irlncRNA pairs significantly correlated with the prognosis of patients were screened out by univariable Cox regression analysis and a prognostic model was constructed by Lasso and multivariate Cox regression analyses. A receiver operating characteristic (ROC) curve was then plotted, with the area under the curve calculated to confirm the reliability of the model. Based on the optimal cutoff value, CRC patients in the high- or low-risk groups were distinguished, laying the ground for evaluating the risk model from the following perspectives: survival, clinicopathological traits, tumor-infiltrating immune cells (TIICs), antitumor drug efficacy, kinase inhibitor efficacy, and molecules related to immune checkpoints.ResultsA prognostic model consisting of 15 irlncRNA pairs was constructed, which was found to have a high correlation with patient prognosis in a cohort from the TCGA (p < 0.001, HR = 1.089, 95% CI [1.067–1.112]). According to both univariate and multivariate Cox analyses, this model could be used as an independent prognostic indicator in the TCGA cohort (p < 0.001). Effective differentiation between high- and low-risk patients was also accomplished, on the basis of aggressive clinicopathological characteristics, sensitivity to antitumor drugs, and kinase inhibitors, the tumor immune infiltration status, and the expression levels of specific molecules related to immune checkpoints.ConclusionThe prognostic model established with irlncRNA pairs is a promising indicator for prognosis prediction in CRC patients.

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The clinical relevance of gene expression based prognostic signatures in colorectal cancer

Cited by 61 publications

References 124 publications

UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

UBE2T promotes autophagy via the p53/AMPK/mTOR signaling pathway in lung adenocarcinoma

Core Circadian Clock Proteins as Biomarkers of Progression in Colorectal Cancer

Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model

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