KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancer

Xu, Jianming; Liu, Xiaojing; Ge, Fei‐Jiao; Wang, Yan; Sharma, Manish; Liu, Zeyuan; Tommasi, Stefania; Paradiso, Angelo

doi:10.1186/preaccept-2062328391321780

Cited by 14 publications

(13 citation statements)

References 16 publications

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“…Even minority of healthy subjects demonstrated mutant KRAS in cfDNA [ 54 ], so the KRAS mutation used for disease diagnosis should be cautious. Generally, the prevalence of KRAS mutations in tumor tissues was high than that of cfDNA in pancreatic cancer and colorectal cancer [ 7 , 42 ]. Previous studies have suggested that the detection of tumor derived cfDNA is more trend in the setting of large tumor burden and tumor high turnover which are both independent predictors of a poor prognosis [ 38 , 48 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis

Zhuang

Wang

et al. 2017

PLoS ONE

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KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information independently. Review Manager 5.3 software was used to perform the statistical analysis. Thirty studies were included in the present meta-analysis. Our analysis showed that KRAS mutation in cfDNA was associated with a poorer survival in cancer patients for overall survival (OS, HR 2.02, 95% CI 1.63–2.51, P<0.01) and progression-free survival (PFS, HR 1.64, 95% CI 1.27–2.13, P<0.01). In subgroup analyses, KRAS mutation in pancreatic cancer, colorectal cancer, non-small cell lung cancer and ovarian epithelial cancer had HRs of 2.81 (95% CI 1.83–4.30, P<0.01), 1.67 (95% CI 1.25–2.42, P<0.01), 1.64 (95% CI 1.13–2.39, P = 0.01) and 2.17 (95% 1.12–4.21, p = 0.02) for OS, respectively. In addition, the ethnicity didn’t influence the prognostic value of KRAS mutation in cfDNA in cancer patients (p = 0.39). Prognostic value of KRAS mutation was slightly higher in plasma than in serum (HR 2.13 vs 1.65), but no difference was observed (p = 0.37). Briefly, KRAS mutation in cfDNA was a survival prognostic biomarker in cancer patients. Its prognostic value was different in various types of cancer.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis

Zhuang

Wang

et al. 2017

PLoS ONE

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“…Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide [ 1 ]. Many improvements have been made in screening, detection and adjuvant therapy for CRC in recent years [ 2 , 3 ]. However, the long-term survival associated with this malignant disease is not satisfactory due to tumor recurrence and metastasis [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

Tan¹,

Zhu²,

Tao³

et al. 2015

J Exp Clin Cancer Res

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BackgroundNeuron navigator 2 (NAV2) encodes a member of the neuron navigator gene family, which plays a role in tumorigenesis and cell migration. However, the prognostic value of NAV2 expression in colorectal cancer (CRC) patients and the potential pathway through which NAV2 promotes migration and invasion in CRC cell lines is poorly understood.MethodsThe expression level of NAV2 was detected in CRC tissues from two different CRC cohorts by immunohistochemistry, qRT-PCR and Western blotting; the correlation between NAV2 expression and clinicopathological characters was analyzed, and the prognostic value of NAV2 expression was analyzed using a Cox regression model. CRC cell lines with NAV2 knocked out were used to validate the function and potential pathway used by NAV2 to promote CRC cell migration and invasion.ResultsThe results showed that NAV2 was overexpressed in CRC tissues, and it was closely correlated with depth of invasion, and lymph and distant metastasis. Multivariate analysis indicated that high NAV2 expression was a poor prognostic indicator of recurrence-free survival and overall survival in CRC patients. Furthermore, Cox regression analysis revealed that high NAV2 expression integrated with high tumor budding grade was a powerful independent predictive factor of CRC clinical outcome. In vitro and in vivo assays demonstrated that knockdown of NAV2 led to reduced migration and invasion of cancer cells, and the process involved the regulation of F-actin polymerization through the SSH1L/cofilin-1 pathway.ConclusionBased on these findings, NAV2 could serve as both a prognostic biomarker and a potential therapeutic target for patients with NAV2-positive CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0237-3) contains supplementary material, which is available to authorized users.

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“…Approximately 60% of patients with mCRC carry the WT KRAS allele, and thus these patients may be appropriate candidates for therapy with EGFR inhibitors [ 4 , 8 , 9 ]. A recent study has suggested that KRAS mutation status is also predictive of long-term prognosis among patients with mCRC treated by conventional chemotherapy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

KRAS testing of patients with metastatic colorectal cancer in a community-based oncology setting: a retrospective database analysis

Carter

Landsman-Blumberg

Johnson

et al. 2015

J Exp Clin Cancer Res

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BackgroundIn 2009, treatment guidelines were updated to recommend KRAS testing at diagnosis for patients with metastatic colorectal cancer (mCRC). We investigated KRAS testing rates over time and compared characteristics of KRAS-tested and not-tested patients in a community-based oncology setting.MethodsAdult patients with a diagnosis of mCRC from 2008–2011 were selected from the ACORN Data Warehouse (ACORN Research LLC, Memphis, TN). Text mining of physician progress notes and full chart reviews identified KRAS-tested patients, test dates, and test results (KRAS status). The overall proportion of eligible patients KRAS-tested in each calendar year was calculated. Among KRAS-tested patients, the proportion tested at diagnosis (within 60 days) was calculated by year. Univariate and multivariate analyses were used to compare patient characteristics at diagnosis between tested and not-tested cohorts, and to identify factors associated with KRAS testing.ResultsAmong 1,363 mCRC patients seen from 2008–2011, 648 (47.5%) were KRAS-tested. Among newly diagnosed mCRC patients, the rate of KRAS testing increased from 5.9% prior to 2008, to 13.9% in 2008, and then jumped dramatically to 32.3% in 2009, after which a modest yearly increase continued. The proportions of KRAS-tested patients who had been diagnosed in previous years but not tested previously increased from 17.7% in 2008 to 27.0% in 2009, then decreased to 19.0% in 2010 and 17.6% in 2011. Among patients who were KRAS-tested, the proportions tested at the time of diagnosis increased annually (to 78.4% in 2011). Patients more likely to have been tested included those with lung metastases, poor performance status, more comorbidities, and mCRC diagnosis in 2009 or later.ConclusionsThe frequency of KRAS testing increased over time, corresponding to changes in treatment guidelines and epidermal growth factor receptor inhibitor product labels; however, approximately 50% of eligible patients were untested during the study period.

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KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancer

Cited by 14 publications

References 16 publications

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis

Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway

KRAS testing of patients with metastatic colorectal cancer in a community-based oncology setting: a retrospective database analysis

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