Expresión de marcadores hipóxicos y glucolíticos CAIX, GLUT-1, HKII y su relación con la respuesta temprana al tratamiento en carcinoma escamocelular de cuello uterino

Moreno‐Acosta, Pablo; Carrillo, Schyrly; Gamboa, Óscar; Acosta, Yineth; Balart-Serra, Joseph; Magné, Nicolas; Melo-Uribe, Mario Alexander; Romero‐Rojas, Alfredo

doi:10.1016/j.pog.2012.09.005

Cited by 4 publications

(11 citation statements)

References 47 publications

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“…Certain previous studies reportd that GLUT1, CAIX, HKII and Hgb level can be considered as biomarkers, suggesting they can be used as prognostic markers for improved therapeutic management of cervical cancer (1,6). The purpose of the present study was to determine whether baseline expression of GLUT1, CAIX and HKII, as well as pre-and post-treatment Hgb levels are associated with treatment response and survival in cancer patients with locally advanced cervical carcinoma.…”

Section: Introductionmentioning

confidence: 90%

“…The clinicopathological characteristics of the patients, as conditions and parameters considered for the making and reading of the immunohistochemistry to GLUT1, CAIX and HKII, were previously described (1). With regards to the expression of GLUT1, CAIX and HKII, a greater increase was observed for the expression of GLUT-1 (74%), followed by CAIX (41%) and HKII (18%).…”

Section: Methodsmentioning

confidence: 99%

“…Previous experimental and clinical studies have shown that cervical cancer tumors are characterized by a highly hypoxic metabolism (1)(2)(3)(4)(5) and a high rate of glycolysis (2,(6)(7)(8). Additionally, these high hypoxic, glycolytic and acidosis metabolisms are implicated in resistance to treatments, including radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Novel predictive biomarkers for cervical cancer prognosis

Moreno‐Acosta

Carrillo

Gamboa

et al. 2016

Molecular and Clinical Oncology

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Abstract. High hypoxic, glycolytic and acidosis metabolisms characterize cervical cancer tumors and have been described to be involved in chemoradioresistance mechanisms. Based on these observations, the present study assessed four selected novel biomarkers on the prognosis of locally advanced cervical carcinoma. A total of 66 patients with stage IIB/IIIB cervical cancer were retrospectively included. The protein expression levels of glucose transporter 1 (GLUT1), carbonic anhydrase 9 (CAIX) and hexokinase 1 (HKII) were investigated by immunohistochemistry on tumor biopsies, hemoglobin was measured and the disease outcome was monitored. A total of 53 patients (80.3%) presented a complete response. For these patients, the protein expression levels of GLUT1, CAIX and HKII were overexpressed. A significant difference was observed (P= 0.0127) for hemoglobin levels (≤11 g/dl) in responsive compared with non-responsive patients. The expression of GLUT1 is associated with a lower rate of both overall and disease-free survival, with a trend of decreased risk of 1.1x and 1.5x, respectively. Co-expression of GLUT1 and HKII is associated with a decreased trend risk of 1.6x for overall survival. Patients with hemoglobin levels ≤11 g/dl had a 4.3-fold risk (P=0.02) in decreasing both to the rate of overall and disease-free survival. The presence of anemic hypoxia (hemoglobin ≤11 g/dl) and the expression of GLUT1 and/or HKII influence treatment response and are associated with a lower overall and disease-free survival. The present results demonstrated that these biomarkers may be used as predictive markers and suggested that these metabolic pathways can be used as potential novel therapeutic targets.

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Section: Introductionmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel predictive biomarkers for cervical cancer prognosis

Moreno‐Acosta

Carrillo

Gamboa

et al. 2016

Molecular and Clinical Oncology

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“…However, the underlying biological phenomenon and the reasons of its variability from one patient to another are still unknown [6]. Different molecular factors involving tissue oxygenation, oncogene activation, loss of tumor suppressor genes and aberrant molecular signaling pathways (such as IGF-1R α and β, CAIX, GLUT-1, GAPDH, HIF-1 alpha, hTERT, Survivin and HKII proteins expressions) were recently identified in CC [3, 7–12]. Crosstalk between glucose metabolism and hypoxia were suggested, and could be the root of resistance to radiotherapy (RT).…”

Section: Introductionmentioning

confidence: 99%

“…Warburg demonstrated in 1927 that most of cancer cells predominantly produced energy by a high rate of anaerobic glycolysis [13]. Recently, it was suggested that cancer cells widely expressed glucose-carrying membrane proteins (GLUT-1, GLUT-7), increasing neoplastic cells metabolism [7, 13–15]. Thus, GLUT-1 was reported to be overexpressed in 47% of CC cells [7, 16–18].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma

et al. 2017

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BackgroundClinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance.MethodsThe present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and β, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS).ResultsOne hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R β was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01).ConclusionsIGF-1R β overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.

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