The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients

Peyravian, Noshad; Larki, Pegah; Gharib, Ehsan; Nazemalhosseini‐Mojarad, Ehsan; Anaraki, Fakhrosadate; Young, Chris; McClellan, James A.; Bonab, Maziar Ashrafian; Asadzadeh‐Aghdaei, Hamid; Zali, Mohammad Reza

doi:10.3390/biomedicines6010027

Cited by 22 publications

(16 citation statements)

References 52 publications

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“…We found that AJCC stage III and IV, which has nodal metastasis or organ metastasis, was associated with OS and DFS in the TCGA database. AJCC TNM stage was established based on OS, and lymph node involvement in itself is considered to have a strong influence on OS and DFS in CRC [16]. In oral squamous cell carcinoma and papillary thyroid carcinoma, GLUT3 was known to be a prognostic marker for OS, and was associated with advanced cancer stage (AJCC TNM stage III and IV) which has nodal metastasis [8, 17].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

et al. 2019

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Background Upregulation of SLC2A genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers. In colorectal cancer, studies reporting the association between overexpression of GLUT and poor clinical outcomes were flawed by small sample sizes or subjective interpretation of immunohistochemical staining. Here, we analyzed mRNA expressions in all 14 SLC2A genes and evaluated the association with prognosis in colorectal cancer using data from the Cancer Genome Atlas (TCGA) database. Methods In the present study, we analyzed the expression of SLC2A genes in colorectal cancer and their association with prognosis using data obtained from the TCGA for the discovery sample, and a dataset from the Gene Expression Omnibus for the validation sample. Results SLC2A3 was significantly associated with overall survival (OS) and disease-free survival (DFS) in both the discovery sample (345 patients) and validation sample (501 patients). High SLC2A3 expression resulted in shorter OS and DFS. In multivariate analyses, high SLC2A3 levels predicted unfavorable OS (adjusted HR 1.95, 95% CI 1.22–3.11; P = 0.005) and were associated with poor DFS (adjusted HR 1.85, 95% CI 1.10–3.12; P = 0.02). Similar results were found in the discovery set. Conclusion Upregulation of the SLC2A3 genes is associated with decreased OS and DFS in colorectal cancer patients. Therefore, assessment of SLC2A3 gene expression may useful for predicting prognosis in these patients. Electronic supplementary material The online version of this article (10.1186/s12885-019-5475-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

et al. 2019

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“…However, most of the cases are asymptomatic until the later stages, and, therefore, the treatment process may not be entirely successful. According to statics, nearly 40% of patients with CRC confront cancer recurrence within 5 years following surgery (Meyerhardt et al, ; Peyravian et al, ).…”

Section: Introductionmentioning

confidence: 99%

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

Arabsorkhi

Gharib

Khojini

et al. 2019

Journal Cellular Physiology

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Evidence indicate that the miR-298 dysregulation might associate with colorectal cancer (CRC) development. Herein, we evaluated the effect of miR-298 dysregulation on colon cancer invasiveness. First, metabolic activity, cell cycle progression, apoptosis, and invasion of miR-298 overexpressed/knocked out colon cancer cells were examined and combined with their transcriptome analysis data for better visualization of miR-298 intracellular signaling networks. Interaction between miR-298 and its target was evaluated with luciferase assay and validated using western blot analysis. The proportion of abnormal miR-298 level was investigated in tumor samples, matched normal adjacent tissues, and plasmas of 100 CRC patients, and also compared with 100 normal plasma samples. TheMann-Whitney U test was performed to assess miR-298 differences among the studied groups, and the correlation between miR-298 and the risk of CRC was shown by univariate and multivariate logistic regression. The data indicate that miR-298 overexpression promoted proliferation and metastasis in CRC cells via targeting phosphatase and tensin homolog. Comparative analysis of CRC tumors, normal adjacent tissues, and plasmas indicated a significant miR-298 upregulation in tumors and plasmas (1.72-fold and 1.65fold, respectively; p < .001). Also, the aberrant level of miR-298 contributed with CRC tumor differentiation, TNM stage and lymph node metastasis (p < .001), and independently associated with poor survival of CRC patients (p < .029; hazard ratio: 1.292; 95% confidence interval: 0.339-2.184). Collectively, these data showed that abnormal level of miR-298 correlated with cancer development and through that lowered the overall survival rate of CRC patients. Therefore, miR-298 could be considered as a therapeutic target for CRC. K E Y W O R D S colorectal cancer, invasion, metastasis, microRNA-298, PTEN

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“…Colon cancer has become a major challenge in medical science for reasons such as high incidence and mortality. Although current therapeutic strategies, including radiotherapy, surgery, and chemotherapy, are widely used in the treatment of patients with early stages of CRC, their efficiency in treating the patients with advanced colon cancer is limited (Peyravian et al, 2018). Cancer recurrence and metastasis are the main obstacles to improving the survival of patients with advanced CRC and therefore, finding new treatment strategies, and effective biomarkers are of particular importance in patients with colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

miR‐497‐5p mediates starvation‐induced death in colon cancer cells by targeting acyl‐CoA synthetase‐5 and modulation of lipid metabolism

Gharib

Nasrabadi

Zali

2020

Journal Cellular Physiology

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Modulation of fatty acids metabolism is an appropriate strategy for starvation‐induced death in tumor cancers. Colon cancer cells express a high level of acyl‐CoA synthetase‐5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5‐related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular‐signaling networks. In vivo analysis was performed using BALB/c mice xenograft model of CRC injected with target miRNA. Clinical significances were also evaluated in 80 CRC tumors and matched adjacent normal tissues. There was a reverse correlation between ACSL5 and miR‐497‐5p, which miR‐497‐5p overexpression modulated CRC cell proliferation and development. A similar observation was received from the in vivo examination in which intratumoral injection of miR‐497‐5p reversed the tumor growth in the CRC xenograft model. Downregulation of miR‐497‐5p correlated with tumor differentiation, tumor, node, and metastasis staging, lymph node metastasis, and poor survival in patients with CRC. These results suggested that miR‐497‐5p upregulation could be considered as a therapeutic strategy for modulation of lipid metabolism in colon cancer.

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The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients

Cited by 22 publications

References 52 publications

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

miR‐497‐5p mediates starvation‐induced death in colon cancer cells by targeting acyl‐CoA synthetase‐5 and modulation of lipid metabolism

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