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Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer

  • Authors:
    • Erick De La Cruz‑Hernández
    • Gabriela Carolina Morales‑Sandoval
    • Marcela Lizano
    • Alejandro Avilés‑Salas
    • Leonardo Josué Castro‑Muñoz
    • Adela Carrillo‑García
    • Maria Del Pilar Ramos‑Godinez
    • Jaime Alberto Coronel‑Martinez
    • Adriana Contreras‑Paredes
  • View Affiliations / Copyright

    Affiliations: Laboratorio de Investigación en Enfermedades Metabólicas e Infecciosas, División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Tabasco 86650, México, Biomedicina Molecular, Instituto Politécnico Nacional, Ciudad de México 07738, México, Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Ciudad de México 14080, México, Departamento de Patología Quirúrgica, Instituto Nacional de Cancerología, Ciudad de México 14080, México, The Wistar Institute, Philadelphia, PA 19104, USA, Subdirección de Investigación Clínica, Instituto Nacional de Cancerología, Ciudad de México 14080, México
    Copyright: © De La Cruz‑Hernández et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 105
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    Published online on: January 12, 2026
       https://doi.org/10.3892/ol.2026.15458
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Abstract

The prognosis of patients with locally advanced cervical cancer (LACC) is often poor due to high treatment resistance. The present study aimed to investigate the association between the levels and localization of SET domain‑containing protein 2 (SETD2) and glioma‑associated oncogene homolog 1 (GLI1) proteins, which are implicated in CC, and their association with clinical outcomes in patients with LACC. In total, 84 patients with LACC diagnosed at Instituto Nacional de Cancerología (México City, México) between January 2016 and December 2018 were analyzed. Immunohistochemical staining was performed to evaluate the expression and localization of SETD2 and GLI1 proteins and immunoreactivity score (IS) was calculated. The association between IS and protein localization and clinicopathological factors and clinical outcomes was examined using the log‑rank test and Cox regression model to investigate the disease‑free survival (DFS) and overall survival (OS). The median age of the cohort was 46 years (range, 25‑81 years). Analysis of SETD2 and IS values according to the sociodemographic and histopathological characteristics of the patients demonstrated that increased nuclear GLI1 (nGLI1) levels were significantly associated with a history of hormonal contraceptive use (P=0.029). Patients with nGLI1 IS >6 exhibited significantly worse OS (P=0.004) and DFS rates (P=0.013) compared with those with nGLI1 (IS <6). The univariate analysis revealed that lower OS was associated with nGLI IS >6 [hazard ratio (HR), 1.50; 95% CI, 1.44‑14.13; P=0.010] and ncGLI1 IS <6 (HR, 1.86; 95% CI, 1.42‑29.5; P=0.016), whereas a lower probability of DFS was significantly correlated with nGLI IS >6 (HR, 1.53; 95% CI, 1.23‑17.49; P=0.023). The present study results demonstrated the utility of IS in evaluating the prognostic impact of SETD2 and GLI1 expression in patients with LACC.

View Figures

Figure 1

Association between GLI1 and SETD2 IS
values according to subcellular localization The linear association
between GLI1 and SETD2 expression was evaluated according to (A)
nuclear and (B) nuclear/cytoplasmic localization of GLI1. GLI1,
glioma-associated oncogene homolog 1; SETD2, SET domain-containing
protein 2; IS, immunoreactivity score; AU, arbitrary unit.

Figure 2

(A) Overall and (B) disease-free
survival in patients with locally advanced cervical cancer
according to nGLI1, ncGLI1 and nSETD2 IS values. Expression levels
were categorized according to the IS value (IS >6 represents
moderate or intense immunoreactivity in >50% area). P-values are
provided by the log-rank (Mantel-Cox) test. Numbers in parentheses
indicate the total number of patients/events. GLI1,
glioma-associated oncogene homolog 1; SETD2, SET domain-containing
protein 2; IS, immunoreactivity score; nc, nuclear and
cytoplasmic.
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Copy and paste a formatted citation
Spandidos Publications style
De La Cruz‑Hernández E, Morales‑Sandoval GC, Lizano M, Avilés‑Salas A, Castro‑Muñoz LJ, Carrillo‑García A, Del Pilar Ramos‑Godinez M, Coronel‑Martinez JA and Contreras‑Paredes A: <p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>. Oncol Lett 31: 105, 2026.
APA
De La Cruz‑Hernández, E., Morales‑Sandoval, G.C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L.J., Carrillo‑García, A. ... Contreras‑Paredes, A. (2026). <p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>. Oncology Letters, 31, 105. https://doi.org/10.3892/ol.2026.15458
MLA
De La Cruz‑Hernández, E., Morales‑Sandoval, G. C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L. J., Carrillo‑García, A., Del Pilar Ramos‑Godinez, M., Coronel‑Martinez, J. A., Contreras‑Paredes, A."<p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>". Oncology Letters 31.3 (2026): 105.
Chicago
De La Cruz‑Hernández, E., Morales‑Sandoval, G. C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L. J., Carrillo‑García, A., Del Pilar Ramos‑Godinez, M., Coronel‑Martinez, J. A., Contreras‑Paredes, A."<p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>". Oncology Letters 31, no. 3 (2026): 105. https://doi.org/10.3892/ol.2026.15458
Copy and paste a formatted citation
x
Spandidos Publications style
De La Cruz‑Hernández E, Morales‑Sandoval GC, Lizano M, Avilés‑Salas A, Castro‑Muñoz LJ, Carrillo‑García A, Del Pilar Ramos‑Godinez M, Coronel‑Martinez JA and Contreras‑Paredes A: <p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>. Oncol Lett 31: 105, 2026.
APA
De La Cruz‑Hernández, E., Morales‑Sandoval, G.C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L.J., Carrillo‑García, A. ... Contreras‑Paredes, A. (2026). <p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>. Oncology Letters, 31, 105. https://doi.org/10.3892/ol.2026.15458
MLA
De La Cruz‑Hernández, E., Morales‑Sandoval, G. C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L. J., Carrillo‑García, A., Del Pilar Ramos‑Godinez, M., Coronel‑Martinez, J. A., Contreras‑Paredes, A."<p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>". Oncology Letters 31.3 (2026): 105.
Chicago
De La Cruz‑Hernández, E., Morales‑Sandoval, G. C., Lizano, M., Avilés‑Salas, A., Castro‑Muñoz, L. J., Carrillo‑García, A., Del Pilar Ramos‑Godinez, M., Coronel‑Martinez, J. A., Contreras‑Paredes, A."<p>Prognostic value of glioma‑associated oncogene homolog 1 and SET domain‑containing protein 2 immunohistochemical scores in locally advanced cervical cancer</p>". Oncology Letters 31, no. 3 (2026): 105. https://doi.org/10.3892/ol.2026.15458
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