Skip to content
DraconiticResearch
Search Sources API
220,795 studies31 sourcesUpdated 27 min ago
Peer-reviewedCC BY-NC-ND 4.0BMC Cancer

Integrative genomic and biophysics analysis of MAPK1 rs1057519911 in cervical cancer: genetic association and therapeutic implications

  • Neelma Hassan1
  • Asad Ullah2
  • Najeeb Ulah Khan1
  • Zainab Jan3
  • Waqas Ahmad1
  • Gadah Albasher4
  • Nouf Al Sultan5
5 affiliations
  1. 1Institute of Biotechnology & Genetic Engineering, The University of Agriculture, Peshawar, KPK 25130 Pakistan
  2. 2Department of Health and Biological Sciences, Abasyn University, Peshawar, KPK 25000 Pakistan
  3. 3Department of Radiation Oncology, Institute of Radiotherapy and Nuclear Medicine, Peshawar, KPK 25120 Pakistan
  4. 4Department of Zoology, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia
  5. 5Department of Medicine, College of Medicine, Nottingham University, Nottingham, UK
Read full textDOICite

Abstract

Human papillomavirus (HPV) infection-related cervical cancer is mostly connected with dysregulated MAPK1 signaling, where genetic variations may alter protein function and affect treatment responses. This study examined the potential treatment implications of the oncogenic missense mutation rs1057519911 in the Mitogen-Activated Protein Kinase-1 (MAPK1) gene in relation to cervical cancer susceptibility. The Tetra-ARMS PCR method was used to genotype 300 participants, comprising 100 HPV-positive patients, 100 HPV-negative patients, and 100 healthy controls. The CT and TT genotypes of MAPK1 rs1057519911 were significantly linked with increased odds of cervical disease, mainly in HPV-positive patients (CT: OR = 15.77, 95% CI: 6.80-36.54; TT: OR = 180.95, 95% CI: 37.99–861.93; both P < 0.001). The T allele was also significantly linked with HPV-negative (OR = 8.73, 95% CI: 5.28–14.44) and HPV-positive disease (OR = 15.22, 95% CI: 9.10-25.46; both P < 0.001), supporting an association between the MAPK1 rs1057519911 variant and cervical disease, mostly HPV-positive disease. The rs1057519911 variant results in an E322K amino acid mutation in MAPK1, prompting further structural and dynamic analyses to evaluate its impact on inhibitor binding. Molecular docking analysis of literature-reported MAPK1 inhibitors against both the wild-type and E322K mutant proteins identified SCH772984 as the highest-affinity ligand for the mutant protein, showing a binding affinity of -9.7 kcal/mol compared with − 8.8 kcal/mol for the wild-type protein. Following 50 ns molecular dynamics simulations and post-MD analyses such as RMSD, RMSF, β-factor, radius of gyration, SASA, and dynamic cross-correlation, the findings showed that the mutant complex was more stable. Binding free energy calculations showed more favorable binding of SCH772984 to the MAPK1 E322K variant, with net binding energies of -73.18 kcal/mol (MM-GBSA) and − 76.72 kcal/mol (MM-PBSA), compared with − 66.22 and − 61.83 kcal/mol, respectively, for wild-type MAPK1. These results provide the first evidence linking MAPK1 rs1057519911 to cervical cancer susceptibility in the Khyber Pakhtunkhwa population and identify SCH772984 as a promising drug candidate for targeted therapy in HPV-associated cervical cancer.

Graphical abstract:

Related

  1. Exerkines in Cardiovascular–Kidney–Metabolic Syndrome: An Integrative Framework for Mechanisms and Therapeutic Implications—A Narrative Review
    Hongyan Fan, Changlin Zhai, Chaojie He +3
    Reviews in cardiovascular medicinePeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  2. STAG2 PROTEIN EXPRESSION IN ADOLESCENT, YOUNG ADULT, AND ELDER PATIENTS WITH MYELODYSPLASTIC NEOPLASMS: ASSOCIATION WITH CYTOGENETIC ALTERATIONS AND THERAPEUTIC IMPLICATIONS
    Beatriz FERREIRA DA SILVA, Nina CARROSSINI BASTOS, Tatiana FONSECA ALVARENGA +6
    Hematology, Transfusion and Cell TherapyPeer-reviewedCC BYFull textEndocrinology & metabolismDOAJ
  3. Argentine Tango as an Integrative Therapeutic Approach: Bridging Dance Therapy and Melotherapy.
    Csongor Kicsi
    Journal of functional morphology and kinesiologyPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  4. Reducing Noise and Alarm Burden in Adult Intensive Care Units: An Integrative Review of Interventions and Implications for Nursing Management
    Wei Jun Dan Ong, Michael Camba Vidanes, Woon Hean Keenan Chong +4
    Journal of Nursing ManagementPeer-reviewedCC BY 4.0Full textSurgery & anaesthesiaPMC
  5. Integrative in vitro, in vivo, and in silico investigation with mineral profiling of Combretum indicum: A multi-target therapeutic candidate exhibiting antioxidant, thrombolytic, anti-inflammatory, anti-arthritic, analgesic, cytotoxic, and anthelmintic activities
    Zobayed Islam, Hridoy Chowdhury, Sujan Kanti Das +3
    PLOS OnePeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationImmunologyPLOS

Cite

BibTeXRIS
BibTeX
@article{hassan2026integrative,
  title = {{Integrative genomic and biophysics analysis of MAPK1 rs1057519911 in cervical cancer: genetic association and therapeutic implications}},
  author = {Neelma Hassan and Asad Ullah and Najeeb Ulah Khan and Zainab Jan and Waqas Ahmad and Gadah Albasher and Nouf Al Sultan},
  journal = {BMC Cancer},
  year = {2026},
  month = sep,
  doi = {10.1186/s12885-026-16946-8},
  url = {https://doi.org/10.1186/s12885-026-16946-8},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Integrative genomic and biophysics analysis of MAPK1 rs1057519911 in cervical cancer: genetic association and therapeutic implications
AU  - Neelma Hassan
AU  - Asad Ullah
AU  - Najeeb Ulah Khan
AU  - Zainab Jan
AU  - Waqas Ahmad
AU  - Gadah Albasher
AU  - Nouf Al Sultan
PY  - 2026
DA  - 2026/09/18
JO  - BMC Cancer
DO  - 10.1186/s12885-026-16946-8
UR  - https://doi.org/10.1186/s12885-026-16946-8
AB  - Human papillomavirus (HPV) infection-related cervical cancer is mostly connected with dysregulated MAPK1 signaling, where genetic variations may alter protein function and affect treatment responses. This study examined the potential treatment implications of the oncogenic missense mutation rs1057519911 in the Mitogen-Activated Protein Kinase-1 (MAPK1) gene in relation to cervical cancer susceptibility. The Tetra-ARMS PCR method was used to genotype 300 participants, comprising 100 HPV-positive patients, 100 HPV-negative patients, and 100 healthy controls. The CT and TT genotypes of MAPK1 rs1057519911 were significantly linked with increased odds of cervical disease, mainly in HPV-positive patients (CT: OR = 15.77, 95% CI: 6.80-36.54; TT: OR = 180.95, 95% CI: 37.99–861.93; both P < 0.001). The T allele was also significantly linked with HPV-negative (OR = 8.73, 95% CI: 5.28–14.44) and HPV-positive disease (OR = 15.22, 95% CI: 9.10-25.46; both P < 0.001), supporting an association between the MAPK1 rs1057519911 variant and cervical disease, mostly HPV-positive disease. The rs1057519911 variant results in an E322K amino acid mutation in MAPK1, prompting further structural and dynamic analyses to evaluate its impact on inhibitor binding. Molecular docking analysis of literature-reported MAPK1 inhibitors against both the wild-type and E322K mutant proteins identified SCH772984 as the highest-affinity ligand for the mutant protein, showing a binding affinity of -9.7 kcal/mol compared with − 8.8 kcal/mol for the wild-type protein. Following 50 ns molecular dynamics simulations and post-MD analyses such as RMSD, RMSF, β-factor, radius of gyration, SASA, and dynamic cross-correlation, the findings showed that the mutant complex was more stable. Binding free energy calculations showed more favorable binding of SCH772984 to the MAPK1 E322K variant, with net binding energies of -73.18 kcal/mol (MM-GBSA) and − 76.72 kcal/mol (MM-PBSA), compared with − 66.22 and − 61.83 kcal/mol, respectively, for wild-type MAPK1. These results provide the first evidence linking MAPK1 rs1057519911 to cervical cancer susceptibility in the Khyber Pakhtunkhwa population and identify SCH772984 as a promising drug candidate for targeted therapy in HPV-associated cervical cancer.  Graphical abstract:
SN  - 1471-2407
ER  -