The effect of genetic alterations detected by the circulating tumor DNAbased next-generation sequencing technique on prognosis and survival in metastatic colorectal cancer

Year 2025, Volume: 18 Issue: 1, 1 - 14, 01.01.2025

Ahmet Ünlü , Atike Gökçen Demiray , Aydın Demiray , Arzu Yaren , Hakan Akça

https://doi.org/10.31362/patd.1482575

Abstract

Purpose: Studies conducted to date showed that circulating tumor DNA (ctDNA)-based next generation
sequencing (NGS) panels are beneficial in the treatment strategies of patients with metastatic colorectal cancer
(mCRC). In this study, we planned to determine the frequencies of various genetic alterations in patients with
mCRC by ctDNA-based NGS analyses, evaluate the concordance rates by comparing these results with
the results in standard polymerase chain reaction (PCR) analyses, and investigate the effect of the detected
alterations on overall survival and progression-free survival.
Materials and methods: The study was conducted by retrospective screening and analysis of the data on 48
patients, who were followed up with a diagnosis of mCRC and who received chemotherapy and/or biological
agents. The data were analyzed using SPSS 25.0 [IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)]
package program.
Results: In this study, ctDNA-based NGS analyses, compared to the quantitative PCR-based gold standard
method, were found to have a sensitivity rate of 64.7%, specificity rate of 55.6% and concordance rate of 59.1%
for KRAS mutation; a sensitivity rate of 100%, specificity rate of 86.7% and concordance rate of 87.1% for NRAS
mutation; a sensitivity rate of 50%, specificity rate of 96.4% and concordance rate of 90.6% for BRAF mutation.
In addition, concordance rates were evaluated based on the time elapsed between the time of taking the liquid
biopsy and tissue biopsy samples. As a result, concordance rates for KRAS, NRAS, and BRAF mutations were
found to be 60.9%, 100%, and 100% respectively, in cases where this elapsed time was less than 6 months;
and were found to be 57.1%, 78.9%, and 85% respectively, in cases where this elapsed time was more than 6
months. Furthermore, the comprehensive analyzes revealed that the frequency of many molecular changes in
mCRC as well as the relationship of these changes with clinicopathological features and survival times.
Conclusion: Our study demonstrates the clinical benefit of ctDNA-based NGS analyzes in patients with mCRC.

Keywords

Colorectal cancer, ctDNA, gene sequencing, liquid biopsy, next generation sequencing

Metastatik kolorektal kanserde dolaşan tümör DNA'sına dayalı yeni nesil dizileme tekniği ile tespit edilen genetik değişikliklerin prognoz ve sağ kalım üzerine etkisi

Abstract

Amaç: Şu ana kadar yapılan çalışmalar; dolaşan tümör DNA'sı (ctDNA) tabanlı next-generation sequencing
(NGS) panellerinin, metastatik kolorektal kanserli (mCRC) hastalarda tedavi stratejilerinde yarar sağladığını
göstermiştir. Biz de bu çalışmamızda; mCRC'li hastalarda ctDNA tabanlı NGS analizleriyle çeşitli gen
değişikliklerinin sıklıklarını saptamayı, bu sonuçları standart polimeraz zincir reaksiyonu (PCR) analizlerindeki
sonuçlarla karşılaştırarak uyum oranlarını değerlendirmeyi ve saptanan değişikliklerin genel sağ kalım ve
progresyonsuz sağ kalıma etkisini araştırmayı planladık.
Gereç ve yöntem: Çalışma; mCRC tanısı ile takip edilen, kemoterapi ve/veya biyolojik ajan alan 48 hastaya ait
bilgilerin retrospektif olarak taranması ve analiz edilmesi ile hazırlandı. Veriler SPSS 25.0 [IBM SPSS Statistics
25 software (Armonk, NY: IBM Corp.)] paket programı kullanılarak analiz edildi.
Bulgular: Çalışmada; ctDNA tabanlı NGS analizlerinin, kantitatif PCR tabanlı altın standart yönteme kıyasla
KRAS mutasyonu için %64,7 duyarlılık, %55,6 özgüllük ve %59,1 uyum oranına; NRAS mutasyonu için %100
duyarlılık, %86,7 özgüllük ve %87,1 uyum oranına; BRAF mutasyonu için %50 duyarlılık, %96,4 özgüllük ve
%90,6 uyum oranına sahip olduğu gösterildi.
Ayrıca, likit biyopsi ile doku biyopsisi örneklerinin alınma zamanları arasındaki süreye göre uyum oranları da
değerlendirildi. Sonuçta; uyum oranları bu süre 6 aydan kısa olanlarda KRAS, NRAS, BRAF mutasyonları
için sırasıyla %60,9, %100, %100 olurken; süre 6 aydan uzun olanlarda sırasıyla %57,1, %78,9, %85 olarak
saptandı. Bunun yanında, yapılan kapsamlı analizler sonucunda; mCRC'de birçok moleküler değişikliğin sıklığı
ve bu değişikliklerin klinikopatolojik özellikler ve sağ kalım süreleriyle ilişkisi ortaya koyuldu.
Sonuç: Çalışmamız; mCRC'li hastalarda, ctDNA tabanlı NGS analizlerinin klinik yararını göstermektedir.

Keywords

ctDNA, gen dizileme, kolorektal kanser, likit biyopsi, yeni nesil dizileme

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