Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study
BackgroundHepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is commonly treated with doxorubicin (DOX). However, its effectiveness varies significantly among patients.AimThe present study aimed to identify potential genetic variants affecting the response of HCC patients t...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604473/full |
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| author | Sireen Abdul Rahim Shilbayeh Naglaa F. Khedr Mohammad A. Alshabeeb Abdulmonem Ali Alsaleh Abdalrhman Hamdan Alanizi Omnia A. Abd El-Baset Rehab H. Werida |
| author_facet | Sireen Abdul Rahim Shilbayeh Naglaa F. Khedr Mohammad A. Alshabeeb Abdulmonem Ali Alsaleh Abdalrhman Hamdan Alanizi Omnia A. Abd El-Baset Rehab H. Werida |
| author_sort | Sireen Abdul Rahim Shilbayeh |
| collection | DOAJ |
| description | BackgroundHepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is commonly treated with doxorubicin (DOX). However, its effectiveness varies significantly among patients.AimThe present study aimed to identify potential genetic variants affecting the response of HCC patients to DOX.Methods78 patients with HCC who received DOX via transarterial chemoembolization (TACE) technology were selected. DNA was extracted from blood for genome-wide genotyping using the Applied Biosystems™ Axiom™ Precision Medicine Diversity Research™ Array. Genetic data were analysed using Axiom™ Analysis Suite software v5.2.ResultsSix hits in five genes [AK3 (rs378117), TRPM3 (rs1329774 and rs4745058), CDH4 (rs2427043), LINC00504 (rs76228864), and GRIN2D (rs76754767)] were associated with a risk of tumour progression, whereas variants in HPGD (rs45593131) and RC3H2 (rs2792999) were suggested as protective factors. rs8038528 in the PCSK6 gene was categorized as a low-response variant associated with an unsatisfactory reduction in α-fetoprotein (AFP) levels after DOX chemotherapy (P = 6.82 × 10−5). In contrast, three SNPs (rs1998853, rs12440990, and rs4774596) located within two genes (NPAS3 and DMXL2) were identified as predictors of good response rates to the treatment, as AFP levels were reduced by ≥ 20%. Death incidents showed associations with five SNPs that reached p ≤ 5.0 × 10−8; four of these are located within the DENND1B, LOC107986086, TMEM169, and RNF152 genes.ConclusionThese findings support the incorporation of pharmacogenomic testing into clinical practice for HCC therapy, paving the way for customized treatment methods that may improve therapeutic efficacy and patient outcomes. Future research is needed to replicate these genetic connections. |
| format | Article |
| id | doaj-art-cd1e851fea8549ceabbaee6563976c89 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-cd1e851fea8549ceabbaee6563976c892025-08-20T03:07:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16044731604473Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association studySireen Abdul Rahim Shilbayeh0Naglaa F. Khedr1Mohammad A. Alshabeeb2Abdulmonem Ali Alsaleh3Abdalrhman Hamdan Alanizi4Omnia A. Abd El-Baset5Rehab H. Werida6Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi ArabiaBiochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, EgyptPharmaceutical Analysis Center, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaBlood and Cancer Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi ArabiaDepartment of Pharmaceutical Care Services, Medical Affairs, King Abdullah Bin Abdulaziz University Hospital, Riyadh, Saudi ArabiaClinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, EgyptDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, EgyptBackgroundHepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is commonly treated with doxorubicin (DOX). However, its effectiveness varies significantly among patients.AimThe present study aimed to identify potential genetic variants affecting the response of HCC patients to DOX.Methods78 patients with HCC who received DOX via transarterial chemoembolization (TACE) technology were selected. DNA was extracted from blood for genome-wide genotyping using the Applied Biosystems™ Axiom™ Precision Medicine Diversity Research™ Array. Genetic data were analysed using Axiom™ Analysis Suite software v5.2.ResultsSix hits in five genes [AK3 (rs378117), TRPM3 (rs1329774 and rs4745058), CDH4 (rs2427043), LINC00504 (rs76228864), and GRIN2D (rs76754767)] were associated with a risk of tumour progression, whereas variants in HPGD (rs45593131) and RC3H2 (rs2792999) were suggested as protective factors. rs8038528 in the PCSK6 gene was categorized as a low-response variant associated with an unsatisfactory reduction in α-fetoprotein (AFP) levels after DOX chemotherapy (P = 6.82 × 10−5). In contrast, three SNPs (rs1998853, rs12440990, and rs4774596) located within two genes (NPAS3 and DMXL2) were identified as predictors of good response rates to the treatment, as AFP levels were reduced by ≥ 20%. Death incidents showed associations with five SNPs that reached p ≤ 5.0 × 10−8; four of these are located within the DENND1B, LOC107986086, TMEM169, and RNF152 genes.ConclusionThese findings support the incorporation of pharmacogenomic testing into clinical practice for HCC therapy, paving the way for customized treatment methods that may improve therapeutic efficacy and patient outcomes. Future research is needed to replicate these genetic connections.https://www.frontiersin.org/articles/10.3389/fphar.2025.1604473/fullgenome-wide association studyhepatocellular carcinomadoxorubicintransarterial chemoembolizationarray genotyping |
| spellingShingle | Sireen Abdul Rahim Shilbayeh Naglaa F. Khedr Mohammad A. Alshabeeb Abdulmonem Ali Alsaleh Abdalrhman Hamdan Alanizi Omnia A. Abd El-Baset Rehab H. Werida Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study Frontiers in Pharmacology genome-wide association study hepatocellular carcinoma doxorubicin transarterial chemoembolization array genotyping |
| title | Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study |
| title_full | Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study |
| title_fullStr | Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study |
| title_full_unstemmed | Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study |
| title_short | Genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy: a genome-wide association study |
| title_sort | genetic polymorphisms as predictors of the response of hepatocellular carcinoma patients to doxorubicin chemotherapy a genome wide association study |
| topic | genome-wide association study hepatocellular carcinoma doxorubicin transarterial chemoembolization array genotyping |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604473/full |
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