KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers

Phipps, Amanda I.; Buchanan, Daniel D.; Makar, Karen W.; Win, Aung Ko; Baron, John A.; Lindor, Noralane M.; Potter, John D.; Newcomb, Polly A.

doi:10.1038/bjc.2013.118

Cited by 222 publications

(185 citation statements)

References 38 publications

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“…30). However, there was no difference, in our cohort, in OS between WT and KRAS-mutant patients (P ¼ 0.675; HR, 1.11; 95% CI, 0.67-1.85), although some authors have reported that the presence of KRAS mutation is indicative of poor outcome (31). Nevertheless, literature analysis tends to show that there is sometimes confusion around the terms prognostic and prediction of therapeutic response.…”

Section: Discussioncontrasting

confidence: 64%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

148

108

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Purpose: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC).Experimental Design: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate).Results: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P ¼ 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P ¼ 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P ¼ 0.0089 and P ¼ 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/ BRAF-mutant cohort of patients (P ¼ 0.0052) and appeared as a strong independent prognostic factor (P ¼ 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P ¼ 0.67).Conclusions: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment.

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Section: Discussioncontrasting

confidence: 64%

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Messaoudi

Moulière

Manoir

et al. 2016

Clinical Cancer Research

148

108

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“…KRAS gene plays a central role in tumor development by regulating the expression of proteins that are involved in cell proliferation and survival, metastasis and angiogenesis. [4][5][6] In colorectal carcinoma, KRAS mutations are present in 30-40% of patients. 7 Activating mutations in KRAS are responsible to anti-EGFR therapy resistance (Cetuximab or Panitumumab) in metastatic colorectal cancer (mCRC).…”

Section: Introductionmentioning

confidence: 99%

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Buim

Fanelli

Souza

et al. 2015

Cancer Biology & Therapy

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Background: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. Objective: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Methods: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). Results: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P D 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Conclusion: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.

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“…KRAS mutations in colon cancer contribute to aggressive cancer phenotype and poorer prognostic [21].…”

Section: Resultsmentioning

confidence: 99%

The N-Hexane Fraction of Myrmecodia Pendans Inhibits Cell Survival and Proliferation in Colon Cancer Cell Line

Bashari¹,

Hidayat²,

Ruswandi³

et al. 2018

Int J Pharm Pharm Sci

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Objective: Despite advanced treatment options available for colorectal cancer, many reported resistance and unresponsiveness to conventional chemotherapeutic agents. Therefore, it is urgent to discover a novel drug for colon cancer. Sarang Semut (Myrmecodia pendans), an Indonesian native plant, has been studied extensively due to its anti-cancer profiles. This study aimed to evaluate the anti-tumour activity of Sarang Semut in colon cancer cells. Methods:We evaluated cytotoxic activity of methanol extract as well as n-hexane and ethyl acetate fraction towards colon cancer cell lines (Caco-2 and HCT-116 cells) utilizing 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The most potent fraction was evaluated further in inhibiting cell survival using MTT assay and cell proliferation using trypan blue exclusion assay as well as a clonogenic assay. Results:Our data showed that the n-hexane fraction of Sarang Semut induces more cell death than the methanol extract and ethyl acetate fraction. Therefore, we analyzed the n-hexane fraction further and found that the inhibitory concentration 50% (IC50 Conclusion:The n-hexane fraction of Sarang Semut demonstrates a high potential antitumor activity in colon cancer cell line.) of the n-hexane fraction was 24 and 30 parts per million (ppm) for Caco-2 and HCT-116 cells, respectively. Moreover, it inhibited cell growth as well as cell colony formation, in particular, shown by the plating efficiency (P<0.05) and colony area per seed (P<0.01) of the control group were different to the treatment group.

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KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers

Cited by 222 publications

References 38 publications

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

The N-Hexane Fraction of Myrmecodia Pendans Inhibits Cell Survival and Proliferation in Colon Cancer Cell Line

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