Oncotype DX® colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: A review of the evidence

You, Y. Nancy; Rustin, Rudolph B.; Sullivan, J. D.

doi:10.1016/j.suronc.2015.02.001

Cited by 78 publications

(51 citation statements)

References 24 publications

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“…Despite that more intensive researches are ongoing, validated predictive markers and effective adjuvant therapies beneficial for stage II or III CRC are lacking [21]. While surgery alone may be curative in 70% of patients with localized (stage II & III) CRC, a proportion of those eventually suffers from tumor recurrence and ultimately dies of metastatic disease [22]. In addition, the benefits of adjuvant therapies remain controversial.…”

Section: Discussionmentioning

confidence: 99%

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Chen

Hou

Gao

et al. 2018

Cell Physiol Biochem

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Background/Aims: The present study was aimed at examining Ezrin expression in human colorectal cancer (CRC) tissues and elucidating the influence of baicalein on the proliferation of HCT116 cells. Methods: The expression of Ezrin was determined by qRT-PCR and immunohistochemistry. HCT116 cells were divided into four groups－ baicalein groups with various concentrations, pcDNA3.1-Ezrin group, si-Ezrin group and dual inhibitory group (baicalein + si-Ezrin). CCK-8 assay and flow cytometry (FCM) were employed to assess cell proliferation and to detect the distribution of cell cycle respectively. The expression levels of Ezrin protein and cell cycle-associated proteins were detected by using western blot. The proliferation ability of CRC cells was also evaluated in vivo. Results: Ezrin expression in CRC tissues was observably higher than that in adjacent colorectal tissues. With drug concentration and action time of baicalein increasing, the cell propagation capacity of HCT116 cells was decreased and the cell cycle progression was arrested. Ezrin expression was inhibited by the administration of baicalein in a dose-dependent way. The levels of CyclinD1 and CDK4 were also significantly decreased, but the expression of P53 pathway proteins P53 and P21 was markedly upregulated. Conclusion: Baicalein repressed proliferation of human colorectal cancer cells HCT116 and blocked cell cycle through downregulating Ezrin and upregulating P53 pathway-related proteins.

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Section: Discussionmentioning

confidence: 99%

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Chen

Hou

Gao

et al. 2018

Cell Physiol Biochem

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“…Our results suggest that the SU-GIB stratification can be developed as a clinical prognostic test for colon cancer, especially since the strength of the test is comparable to that of an in silico adapted version of Oncotype DX colon. Obviously extensive validation studies are required to define the best patient group that would benefit from the SU-GIB test, as has been done previously for others 13, 14. This would need to be followed by studies that would assess if treatment decisions can be altered by the SU-GIB test, which is considered a major criterion for clinical usability 15.…”

Section: Discussionmentioning

confidence: 99%

A Combined ULBP2 and SEMA5A Expression Signature as a Prognostic and Predictive Biomarker for Colon Cancer

Demirkol¹,

Gömceli²,

Isbilen³

et al. 2017

J. Cancer

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Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers.Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p≤0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(®) in predicting recurrence in two different cohorts (HR: 1.5-2; p≤0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype.Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature.

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“…Some authors suggest the evaluation of molecular tumor biomarkers in all stage II colon cancer patients in order to define which patients may benefit from adjuvant treatment. 30 Our survival analysis using the current accepted definition of “high-risk” tumors, though would be stronger with greater patients numbers, adds information to the current available literature on the topic, and furthermore, helps us highlight a critical issue, which is that current definitions of risk are likely incomplete. Further prospective trials should focus on identifying stage II colon cancer patients with high-risk features and/or high-risk gene expression profiles in order to better select patients for adjuvant treatment.…”

Section: Discussionmentioning

confidence: 91%

Utilization and impact of adjuvant chemotherapy among patients with resected stage II colon cancer: a multi-institutional analysis

Ejaz

Casadaban

Maker

2017

Journal of Surgical Research

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Background The use of chemotherapy among patients with stage II colon cancer is controversial. We aimed to define the utilization and factors associated with the receipt of chemotherapy and the impact of chemotherapy on long-term prognosis among a large, multi-institutional cohort of patients. Materials and Methods We identified 876 patients who underwent resection for stage II colon cancer between 2004 and 2013 at one of 7 participating institutions. Overall (OS) and recurrence-free (RFS) survival time was calculated from the date of the index procedure to the date of death. Results 163 patients (18.6%) received adjuvant chemotherapy and this utilization decreased over time (P=0.003). Younger age (P<0.001), margin positivity (OR 12.16, 95%CI 2.57–57.52; P=0.002) and the presence of perineural invasion (OR 1.24, 95%CI 1.07–1.44; P=0.005) increased the likelihood of receiving chemotherapy. Receipt of chemotherapy was associated with improved median OS and RFS. After controlling for all factors, the addition of oxaliplatin to 5-flurorouracil did not affect survival, and there was no difference in OS (HR: 0.74, 95%CI 0.27–2.06; P=0.57) or RFS (HR 0.71, 95%CI 0.32–1.58; P=0.88) with adjuvant treatment, including for patients with high-risk features (OS - HR: 0.63, 95%CI 0.33–1.19; P=0.15; RFS - HR: 0.77, 95%CI 0.32–1.86; P=0.56). Conclusions The utilization of chemotherapy has declined over time after resection for stage II colon cancer. Chemotherapy was not independently associated with improved OS or RFS in this study group, including in patients with high-risk features. Future prospective studies should strive to identify the subset of stage II colon cancer patients that will benefit the most from the addition of adjuvant chemotherapy.

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Oncotype DX® colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: A review of the evidence

Cited by 78 publications

References 24 publications

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

A Combined ULBP2 and SEMA5A Expression Signature as a Prognostic and Predictive Biomarker for Colon Cancer

Utilization and impact of adjuvant chemotherapy among patients with resected stage II colon cancer: a multi-institutional analysis

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