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ORIGINAL RESEARCH ARTICLE
Identifying KRAS mutations in non-small cell lung cancer of Iraqi patients
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1 Department of Molecular and Medical Biotechnology, College of Biotechnology, Al-Nahrain University, Baghdad,
Iraq
Received: 11 August 2025 | Revised: 4 December 2025 | Accepted: 7 January 2026 | Published online: 10 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract
Lung cancer remains one of the most common malignancies. It is usually categorized into two types: small-cell lung cancer and non-small-cell lung cancer (NSCLC). Among the types of NSCLC, adenocarcinoma is the most common and is more prevalent in women than in men. The current study aims to identify KRAS mutations in a population with metastatic lung cancer. Moreover, the clinical significance of the KRAS mutations was also explored. For this purpose, KRAS status was evaluated by polymerase chain reaction and reverse hybridization. According to the molecular results, mutations were observed at codons 12, 13, 59, 61, 117, and 146. Interestingly, the number of patients with stage II disease was significantly higher, indicating that the type of KRAS alteration may be associated with early disease spread. Thus, these mutations were associated with poor responses to cetuximab and panitumumab, underscoring the important role of KRAS profiling in strategizing treatment modifications. We can also conclude that molecular diagnostics plays its role in everyday clinical practice by complementing precision oncology and improving the outlook for patients with NSCLC.
Keywords
Non-small cell lung carcinoma
KRAS alteration
Mutation
Molecular profiling
Reverse hybridization assay
FFPE tissue
Funding
None.
Conflict of interest
The author declares no conflict of interest.
References
- Puig de la Bellacasa R, Karachaliou N, Estrada-Tejedor R, Teixidó J, Costa C, Borrell JI. ALK and ROS1 as a joint target for the treatment of lung cancer: A review. Transl Lung Cancer Res. 2013;2(2):72-86. doi: 10.3978/j.issn.2218-6751.2013.03.11
- Cheng X, Liu J, Hu Q, Gao Y, Zhou L. A novel secondary ALK gene mutation which resistant to second-generation TKIs: a case report and literature review. Front Oncol. 2024;14:1430350. doi: 10.3389/fonc.2024.1430350
- Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. doi: 10.3322/caac.20138
- Patel SA, Weiss J. Advances in the treatment of non-small cell lung cancer: Immunotherapy. Clin Chest Med. 2020;41(2):237-247. doi: 10.1016/j.ccm.2020.02.010
- Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer. 2021;20(1):143. doi: 10.1186/s12943-021-01441-4
- Siddiqui AD, Piperdi B. KRAS mutation in colon cancer: a marker of resistance to EGFR-I therapy. Ann Surg Oncol. 2010;17(4):1168-1176. doi: 10.1245/s10434-009-0811-z
- Zhang Y, Wang Y, Zhang B, Li P, Zhao Y. Methods and biomarkers for early detection, prediction, and diagnosis of colorectal cancer. Biomed Pharmacother. 2023;163:114786. doi: 10.1016/j.biopha.2023.114786
- Tsantoulis P, Hong Y, Wirapati P, et al. A single-sample gene-expression classifier for the intrinsic consensus molecular subtypes (iCMS) of colorectal cancer. J Clin Oncol. 2024;42(16_suppl):e15587. doi: 10.1200/JCO.2024.42.16_suppl.e15587
- Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in cancer. Cancer Res. 2020;80(14):2969-2974. doi: 10.1158/0008-5472.CAN-19-3682
- Bungaro M, Novello S, Passiglia F. Targeting KRASp.G12C mutation in advanced non-small cell lung cancer: A new era has begun. Curr Treat Options Oncol. 2022;23(12):1699-1720. doi: 10.1007/s11864-022-01033-4
- Chen N, Fang W, Lin Z, et al. KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma. Cancer Immunol Immunother. 2017;66(9):1175-1187. doi: 10.1007/s00262-017-2005-z
- Sarnecka AK, Nawrat D, Piwowar M, Ligęza J, Swadźba J, Wójcik P. DNA extraction from FFPE tissue samples - a comparison of three procedures. Contemp Oncol. 2019;23(1):52-58. doi: 10.5114/wo.2019.83875
- Singh H, Narayan B, Urs AB, Kumar Polipalli S, Kumar S. A novel approach for extracting DNA from formalin-fixed paraffin-embedded tissue using microwave. Med J Armed Forces India. 2020;76(3):307-311. doi: 10.1016/j.mjafi.2019.02.007
- Lam SY, Ioannou A, Konstanti P, et al. Technical challenges regarding the use of formalin-fixed paraffin embedded (FFPE) tissue specimens for the detection of bacterial alterations in colorectal cancer. BMC Microbiol. 2021;21(1):297. doi: 10.1186/s12866-021-02359-z
- Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164. doi: 10.3322/caac.21601
- Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer — a call to action. Nat Rev Clin Oncol. 2020;18(4):230-243. doi: 10.1038/s41571-020-00445-1
- Araghi M, Soerjomataram I, Bardot A, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol Hepatol. 2019;4(7):511-518. doi: 10.1016/s2468-1253(19)30147-5
- Huang JF, Zeng DZ, Duan GJ, et al. Single-tubed wild-type blocking quantitative PCR detection assay for the sensitive detection of codon 12 and 13 KRAS mutations. PLoS One. 2015;10(12):e0145698. doi: 10.1371/journal.pone.0145698
- Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626-1634. doi: 10.1200/JCO.2007.14.7116
- Smith G, Bounds R, Wolf H, Steele RJC, Carey FA, Wolf CR. Activating K-Ras mutations outwith ‘hotspot’ codons in sporadic colorectal tumours – implications for personalised cancer medicine. Br J Cancer. 2010;102(4):693-703. doi: 10.1038/sj.bjc.6605534
- Kavgaci G, Akiva I, Ozon YH, et al. Evaluation of KRAS and NRAS mutations in metastatic colorectal cancer: An 8-year study of 10754 patients in Turkey. Mol Oncol. 2025;19(10):2967-2977. doi: 10.1002/1878-0261.70042
- Naseri M, Sebzari A, Haghighi F, Hajipoor F, Emadian Razavi F. Frequency of K-RAS and N-RAS gene mutations in colorectal cancers in Southeastern Iran. Asian Pac J Cancer Prev. 2016;17(9):4511-4515.
- Takeda M, Yoshida S, Inoue T, et al. The role of KRAS mutations in colorectal cancer: biological insights, clinical implications, and future therapeutic perspectives. Cancers. 2025;17(3):428. doi: 10.3390/cancers17030428
- Yang Q, Huo S, Sui Y, et al. Mutation Status and Immunohistochemical Correlation of KRAS, NRAS, and BRAF in 260 Chinese Colorectal and Gastric Cancers. Front Oncol. 2018;8:487. doi: 10.3389/fonc.2018.00487
- Persikov AV, Pillitteri RJ, Amin P, Schwarze U, Byers PH, Brodsky B. Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Hum Mutat. 2004;24(4):330-337. doi: 10.1002/humu.20091
- Mondal K, Posa MK, Shenoy RP, Roychoudhury S. KRAS mutation subtypes and their association with other driver mutations in oncogenic pathways. Cells. 2024;13(14):1221. doi: 10.3390/cells13141221
- Nuytinck L, Tükel T, Kayserili H, Yüksel Apak M, De Paepe A. Glycine to tryptophan substitution in type I collagen in a patient with OI type III: A unique collagen mutation. J Med Genet. 2000;37(5):371-375. doi: 10.1136/jmg.37.5.371
- Hasbullah HH, Sulong S, Che Jalil NA, Abdul Aziz AA, Musa N, Musa M. KRAS mutational profiles among colorectal cancer patients in the East Coast of Peninsular Malaysia. Diagnostics. 2023;13(5):822. doi: 10.3390/diagnostics13050822
- Janakiraman M, Vakiani E, Zeng Z, et al. Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res. 2010;70(14):5901-5911. doi: 10.1158/0008-5472.CAN-10-0192
- Edkins S, O’Meara S, Parker A, et al. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther. 2006;5(8):928-932. doi: 10.4161/cbt.5.8.3251