Concordance of KRAS Mutation in Tumor Tissues and Fecal Samples of Colorectal Carcinoma Patients

Ahmad Bahrudin, Reno Rudiman, Andriana Purnama, Kiki Lukman, Yunia Sribudiani, Prapanca Nugraha

Abstract


BACKGROUND: Colorectal cancer (CRC) is a major global health problem associated with high cancer-related mortality. Profiling of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status has become a decisive predictive biomarker in the management of CRC. However, KRAS mutation testing is commonly performed using tumor tissue obtained through invasive biopsy or surgery; therefore, fecal DNA analysis might offer a promising non-invasive alternative. This study was conducted to evaluate the concordance of KRAS mutations between matched tumor tissue and fecal samples and their association with clinicopathological characteristics.

METHODS: This cross-sectional study included 94 patients confirmed of CRC. Tumor tissue specimens were obtained during surgical resection or biopsy, while fecal samples were collected pre-operatively. KRAS mutations were analyzed using polymerase chain reaction (PCR) and DNA sequencing, and the associations with clinicopathological variables were statistically evaluated.

RESULTS: KRAS mutations were detected in 45.74% of tumor tissue and 26.60% of fecal samples. The overall concordance rate was 65.96%, with a Cohen’s Kappa of 0.291 (95% CI: 0.110–0.472), indicating "fair agreement". Notably, allele-specific concordance was 100% among double-positive cases. The fecal assay demonstrated 41.86% sensitivity, 86.27% specificity, 72.00% positive predictive value (PPV), and 63.77% negative predictive value (NPV). Tumor location (colon versus rectum) was significantly associated with fecal KRAS detection (p=0.028); other variables showed no significant association (p>0.05).

CONCLUSION: KRAS mutations were more frequently detected in tissue than in fecal samples, with fair agreement. High allele-specific concordance suggests fecal DNA accurately reflects the tumor's mutational profile. Tumor location significantly influences DNA detectability, supporting fecal-based KRAS testing as a potential non-invasive approach for CRC molecular assessment.

KEYWORDS: colorectal neoplasms, feces, KRAS protein, human, mutation, neoplasm tissue


Full Text:

PDF

References


Hossain MdS, Karuniawati H, Jairoun AA, Urbi Z, Ooi DJ, John A, et al. Colorectal cancer: A review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies. Cancers. 2022; 14(7): 1732, CrossRef.

Wijaya T, Akmal AAM, Herman N, Hasan AA, Hafiz A, Widyastuti H. Apoptotic effects sulfated polysaccharides of Caulerpa racemosa extract on colorectal cancer cells through caspase-3. Mol Cell Biomed Sci. 2025; 9(3): 171-8, CrossRef.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-49, CrossRef.

Tedjasaputra TR, Hatta M, Massi MN, Natzir R, Patellongi I, Simadibrata M, et al. Risk assessment in hereditary colorectal cancer family by using APC and MSH2 mRNA gene expression and bayesian analysis. Indones Biomed J. 2020; 12(4): 368-75, CrossRef.

Rianti AM, Cangara MH, Yamin A, Dahlan H, Ilyasa MR, Miskad UA. FGFR2 as a prognostic and predictive marker in colorectal adenocarcinoma based on TILs grade. Indones Biomed J. 2025; 17(2): 188-96, CrossRef.

Luminturahardjo W, Soeatmadji DW, Mintaroem K, Rahajoe P, Sandra F. N-cadherin as an important marker in colorectal cancer: An investigation of β-catenin and cadherin expressions of SW-480 and HCT-116 cell lines. Indones Biomed J. 2021; 13(3): 289-94, CrossRef.

Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Kao LS, Hunter JG, et al. Schwartz's Principles of Surgery. 11th ed. New York: McGraw-Hill Education; 2019, NLMID.

Yamagishi H, Kuroda H, Imai Y, Hiraishi H. Molecular pathogenesis of sporadic colorectal cancers. Chin J Cancer. 2016; 35(1): 4, CrossRef.

Ferretti S, Patriarca S, Carbone A, Zanetti R. TNM classification of malignant tumours, VII edition 2009. Changes and practical effects on cancer epidemiology. Epidemiol Prev. 2010; 34(3): 125-8.

Semadhi MP, Prasojo SL, Widarini A. Lung cancer: Biomarkers, tyrosine kinase inhibitors and monoclonal antibodies. Mol Cell Biomed Sci. 2017; 1(2): 41-9, CrossRef.

Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021, NLMID.

Porru M, Pompili L, Caruso C, Biroccio A, Leonetti C. Targeting KRAS in metastatic colorectal cancer: Current strategies and emerging opportunities. J Exp Clin Cancer Res. 2018; 37(1): 57, CrossRef.

Warsinggih, Liliyanto, Marhamah, Kusuma MI, Uwuratuw JA, Syarifuddin E, et al. Relationship between BRAF V600E and KRAS mutations in stool for identifying colorectal cancer: A cross-sectional study. Ann Med Surg. 2020; 60: 121-5, CrossRef.

The American College of Surgeons [Internet]. AJCC Cancer Staging Form Supplement AJCC Cancer Staging Manual, Eighth Edition [cited 2025 Jan 15]. Available from: https://www.facs.org/.

Mo S, Wang H, Han L, Xiang W, Dai W, Zhao P, et al. Fecal multidimensional assay for non-invasive detection of colorectal cancer: Fecal immunochemical test, stool DNA mutation, methylation, and intestinal bacteria analysis. Front Oncol. 2021; 11: 643136, CrossRef.

Xu H, Chen H, Hu J, Xiong Z, Li D, Wang S, et al. Feasibility of quantification based on novel evaluation with stool DNA and fecal immunochemical test for colorectal cancer detection. BMC Gastroenterol. 2022; 22(1): 384, CrossRef.

Wang Z, Shang J, Zhang G, Kong L, Zhang F, Guo Y, et al. Evaluating the clinical performance of a dual-target stool DNA test for colorectal cancer detection. J Mol Diagn. 2022; 24(2): 131-43, CrossRef.

Sui X, Chen Y, Liu B, Li L, Huang X, Wang M, et al. The relationship between KRAS gene mutation and intestinal flora in tumor tissues of colorectal cancer patients. Ann Transl Med. 2020; 8(17): 1085, CrossRef.

Dong Z, Kong L, Wan Z, Zhu F, Zhong M, Lv Y, et al. Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients. Sci Rep. 2019; 9(1): 16894, CrossRef.

Moore KL, Agur AMR, Dalley AF II. Clinically Oriented Anatomy. 8th ed. Philadelphia: Wolters Kluwer; 2018, NLMID.

Zanatto RM, Santos G, Oliveira JC, Pracucho EM, Nunes AJF, Lopes-Filho GJ, et al. Impact of KRAS mutations in clinical features in colorectal cancer. Arq Bras Cir Dig. 2020; 33(3): e1524, CrossRef.

Alghamdi M, Alabdullatif N, Al-Rashoud A, Alotaibi J, Alhussaini N, Elsirawani S, et al. KRAS mutations in colorectal cancer: Relationship with clinicopathological characteristics and impact on clinical outcomes in Saudi Arabia. Cureus. 2022; 14(3): e23656, CrossRef.

Rudiman R, Alfarisy A, Lukman K, Nugraha P, Setiawan Y, Sribudiani Y. Associations of KRAS mutations and clinical characteristics of colorectal cancer patients in Indonesia. Asian Pac J Cancer Prev. 2024; 25(10): 3457-61, CrossRef.

Faroque H, Aria NS, Muzilah NA, Al-Jamal HAN, Rahim MFA, Nakamura Y, et al. CHEK1 and GFPT1 as potential blood-based biomarkers for colorectal cancer. Indones Biomed J. 2023; 15(6): 358-65, CrossRef.




DOI: https://doi.org/10.18585/inabj.v18i4.4279

Copyright (c) 2026 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 Indexed by:

                  

                     

          

 

 

The Prodia Education and Research Institute