Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer

Xiao, Qiu; Feng, Jianhua; Wang, Fan; Chen, Peng‐Fei; Chen, Xiao‐Xing; Zhou, Rui; Chang, Ying; Liu, Jing; Zhao, Qiu

doi:10.3892/mmr.2017.8210

Cited by 11 publications

(9 citation statements)

References 31 publications

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“…Our results provide further evidence for use of NEBL gene expression as an independent predictor for CRC prognosis. Higher expression of NEBL was reported to be predictor for better outcome and is in conformity with our results [32]. Our independent analysis of indigenous data based on local population samples from matched tumor normal samples provide confidence in use of NEBL gene as a putative prognostic biomarker.…”

Section: Discussionsupporting

confidence: 91%

HHLA2 and NEBL as novel prognostic biomarkers based on Rayleigh survival model in colorectal cancer

Khan

Aziz

Alatar

et al. 2021

Preprint

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Background The primary focus for this study was investigation of prognostic biomarkers in colorectal cancer (CRC), since biomarkers are instrumental in clinical decision making and patient management as well as playing pivotal roles in precision medicine.Methods We analyzed indigenous dataset from colorectal cancer patients. Exon microarray dataset was used and 135 genes were identiﬁed as novel candidate biomarkers. 135 genes were further split into two groups: low and high gene expression values via ’maxstat’ algorithm, they were analyzed using Kaplan-Meier (K-M) analysis and univariate Cox model, and a set of 33 genes were identiﬁed as statistically signiﬁcant (p¡0.05). Furthermore, using the ’VARCLUS’ algorithms (a SAS software procedure) which is a useful tool for variable reduction, based on the divisive clustering techniques, a small subset of 5 genes were selected out of 33 signiﬁcant genes as potential candidates to build survival models. Both parametric and semi-parametric survival models were utilized to assess whether these 5 genes could be used as prognostic biomarkers.Results HHLA2 (p < 0.01) and NEBL (p < 0.01) genes emerged as potential biomarkers, based on the para- and semi-parametric models such as: Rayleigh, Exponential probability distributions, and Cox models and were also validated on independent datasets, apart from validation with qPCR test as well as with the cell lines patients data in the laboratory. A rigorous statistical evaluation for model’s performance were done via Harrell’s index, Brier score, Shoenfeld residual plots as well as with comparing several predictive model plots. We also made the comparison of Akaike and Bayesian Information(AIC and BIC) criteria as well as log-likelihood estimates. The Tukey-Anscome plot and Quantile-Quantile plot as diagnostic tools were applied to validate the parametric survival models. Conclusion Based on predictive models HHLA2 and NEBL novel biomarkers were found as statically signiﬁcant.

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Section: Discussionsupporting

confidence: 91%

HHLA2 and NEBL as novel prognostic biomarkers based on Rayleigh survival model in colorectal cancer

Khan

Aziz

Alatar

et al. 2021

Preprint

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“…NEBL and Akt1 are the biological markers of the cancer staging. 38 , 43 , 44 A higher level of NEBL expression was detected in HCT116 and all of the higher-stage cells of primary tumor cell cultures in the current study before induction of VSV M-protein expression. Suppressing the Akt1 expression has shown to promote apoptosis in higher stages of colorectal cancer cells.…”

Section: Discussionsupporting

confidence: 46%

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

Mamizadeh

Kalani

Parsania

et al. 2021

Molecular Therapy - Oncolytics

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This study compares the oncolytic effect of vesicular stomatitis virus (VSV) wild type and M51R M-protein on the colorectal tumors of different invasive intensity on SW480 and HCT116 cell lines and 114 fresh colorectal cancer primary cell cultures. Fresh tumor samples were divided into two groups of lower stages (I/II) and higher stages (III/IV) regarding the medical records. The presence of two mutations in the PIK3CA gene and the expression of NEBL and AKT1 genes were evaluated. The cells were transfected with a plasmid encoding VSV wild-type and M51R mutant M-protein. Results showed either wild type or M51R mutant can kill SW480 and stage I/II primary cultures while mutant M-protein had no apoptotic effects on HCT116 cells and stage III/IV primary cultures. NEBL and AKT1 expression were significantly higher in resistant cells. Elevated caspase-9 activity confirmed that the intrinsic apoptosis pathway is the reason for cell death in lower-stage cells. Different tumors from the same cancer exhibit different treatment sensitivity due to genetic difference. NEBL and AKT1 gene expression may be responsible for this difference, which may be the target of future investigations. Therefore, tumor staging should be considered in oncolytic viral treatment as an interfering factor.

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“…Although this gene is over-expressed in CRC, but the over-expression of NEBL was associated with longer overall survival of the patients. 21 …”

Section: Discussionmentioning

confidence: 99%

Nebulette Expression Is Associated with Lymph Node Metastasis in Patients with Colorectal Cancer

Hosseini

Mahjoubi

Majidzadeh

et al. 2018

Middle East J Dig Dis

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BACKGROUND Colorectal cancer (CRC) is one of the most common cancers among men and women worldwide. Cancer metastasis is the main cause of death in patients with cancer. NEBL (nebulette, Gene ID: 10529) protein interacts with thin filaments in the cell and may functionally destabilize focal adhesion composition. There are some studies on NEBL gene expression alteration in cancer. In the presented study we aimed to analyze NEBL gene expression in patients with colorectal cancer to explore possible association of this gene with clinicopathological features in CRC. METHODS Sixty-seven fresh samples of colorectal tumors and adjacent normal tissues were collected from Iranian patients with CRC. Real time polymerase chain reaction was performed to measure the level of NEBL gene expression and its association with clinico-pathological features. RESULTS A significant overexpression with 3 fold increse was seen in NEBL mRNA level in tumoral tissues compared with the adjacent normal tissues. In addition there was a significant association between NEBL gene expression with lymph node metastasis in patients with CRC. CONCLUSION The overexpression of NEBL has the capacity to be considred as a prognostic biomarker in patients with CRC.

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Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer

Cited by 11 publications

References 31 publications

HHLA2 and NEBL as novel prognostic biomarkers based on Rayleigh survival model in colorectal cancer

HHLA2 and NEBL as novel prognostic biomarkers based on Rayleigh survival model in colorectal cancer

NEBL and AKT1 maybe new targets to eliminate the colorectal cancer cells resistance to oncolytic effect of vesicular stomatitis virus M-protein

Nebulette Expression Is Associated with Lymph Node Metastasis in Patients with Colorectal Cancer

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