Dataset Information

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

ABSTRACT:

Background

The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence.

Methods

Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of 84 patients with CRC with KRAS mutation (exon 4 p.A146T, exon 4 p.A146V, exon 2 p.G12A, exon 2 p.G12C, exon 2 p.G12D, exon 2 p.G12S, exon 2 p.G12V, exon 2 p.G13D, exon 3 p.Q61H) and analyzed using the digital polymerase chain reaction system. The median observation period was 26 months.

Results

Although the relationship between the perioperative MAF of KRAS and recurrence was not proved, tumor diameter, tumor depth, and stage were correlated with the preoperative MAF of KRAS (p = 0.034, p = 0.002, p = 0.008). However, tumor diameter, tumor depth, and stage did not correlate with MAF of KRAS at postoperative day 30.

Conclusions

In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.

SUBMITTER: Hayashi T

PROVIDER: S-EPMC9385586 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

Hayashi Takaomi T Yoshida Yoichiro Y Yamada Teppei T Tanaka Keita K Shimaoka Hideki H Kajitani Ryuji R Munechika Taro T Nagano Hideki H Matsumoto Yoshiko Y Komono Akira A Sakamoto Ryohei R Aisu Naoya N Yoshimatsu Gumpei G Yoshimura Fumihiro F Hasegawa Suguru S

Cancer medicine 20220321 16

<h4>Background</h4>The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence.<h4>Methods</h4>Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of ...[more]

PMID: 35312176

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Project description:BackgroundColorectal cancer is among the most prominent malignant tumors endangering human health, with affected populations exhibiting an increasingly younger trend. The Kirsten ras (KRAS) gene acts as a crucial regulator in this disease and influences multiple signaling pathways. In the present study, the KRAS gene mutation-induced alteration of intestinal flora in colorectal cancer patients was explored, and the intestinal microbes that may be affected by the KRAS gene were examined to provide new insights into the diagnosis and treatment of colorectal cancer.MethodsDeoxyribonucleic acid (DNA) was extracted from 177 colorectal cancer patients in our hospital. The mutation of the KRAS gene was subsequently detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), and survival analysis was performed. Moreover, genomic DNA was extracted from the fecal microbes in 30 of these patients, and the differences in the intestinal flora between mutation and non-mutation groups were evaluated using linear discriminant analysis (LDA) Effect size (LEfSe) analysis.ResultsKRAS gene mutation substantially affected the distant metastasis of colorectal cancer, and the survival prognosis in the non-mutation group was significantly superior compared to the mutation group. The mutation group had a notably higher prevalence of microbes including Roseburia, Parabacteroides, Metascardovia, Staphylococcus, Staphylococcaceae, and Bacillales than the non-mutation group. The presence of microbes in the non-mutation group, such as Clostridiales, Bacteroidetes, Lachnospiraceae, Coprococcus, and Ruminococcaceae was markedly higher than in the mutation group. Firmicutes were negatively correlated with the presence of Actinomyces and Bacteroidetes, while Bacteroidetes were positively associated with the level of Actinomyces.ConclusionsIn colorectal cancer, KRAS gene mutation can remarkably affect the survival prognosis and change the composition and abundance of intestinal flora, such as Roseburia, Parabacteroides, Metascardovia, Staphylococcus, and Bacillales, thereby influencing tumor development.

Project description:IntroductionCirculating tumor DNA (ctDNA) has been increasingly recognized as a promising minimally-invasive biomarker that could identify patients with minimal residual disease and a high risk of recurrence after definitive treatment. In this study, we've compared the clinical utility and sensitivity of 2 different approaches to ctDNA analyses: tumor-informed and tumor-agnostic in the management of colorectal (CRC) patients. The clinical benefits of a single timepoint ctDNA analysis compared to serial ctDNA monitoring after definitive treatment were also evaluated to uncover the ideal surveillance protocol.MethodsPatient-paired resected tumor tissues, peripheral blood cells, and a total of 127 pre-operative and serial plasma cell-free DNA (cfDNA) samples after definitive treatment from 38 CRC patients that had undergone curative intent surgery were analyzed using a commercial NGS cfDNA panel.ResultsUp to 84% (32/38) of the recruited patients were detected with at least 1 genomic alteration from the tumor tissues that could be monitored using the tumor-informed ctDNA approach and none of the detected alterations were clonal hematopoiesis (CH) related. In contrast, 37% (14/38) of patients were detected with at least 1 monitoring alteration after exclusion of CH mutations using the tumor-agnostic approach. Serial plasma samples after definitive therapy were available for 31 patients. In the landmark ctDNA analysis, 24% (7/29) of patients had detectable ctDNA and were more likely to relapse than ctDNA-negative patients (p < 0.05). The landmark analysis sensitivity and specificity for recurrence were 67% and 87%, respectively. The incorporation of longitudinal ctDNA analysis at 6-months intervals improved the sensitivity to 100%. The median variant allele frequency (VAF) of the ctDNA mutations detected during surveillance was 0.028% (range: 0.018-0.783), where up to 80% (8/10) of the mutations were detected at VAF lower than the tumor-agnostic detection limit of 0.1%. Utilizing the tumor-agnostic approach reduced the recurrence detection sensitivity to 67% (4/6). Serial ctDNA analyses predicted disease recurrence at a median of 5 months ahead of radiological imaging.ConclusionLongitudinal monitoring using tumor-informed ctDNA testing shows high analytical sensitivity, low probability of false-positive results due to CH mutations, and improved sensitivity in detecting recurrence which may modify the clinical management of CRC.

Dataset Information

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

Background

Methods

Results

Conclusions

Publications

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

Similar Datasets

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