IGF1R gene expression as a predictive marker of response to ionizing radiation for patients with locally advanced HPV16-positive cervical cancer.
OBJECTIVE
The aim of this study was to evaluate the predictive utility of Insulin-like growth factor-1 receptor (IGF1R), IGF1, IGF2, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and of hemoglobin levels for tumor response to exclusive radiotherapy, in patients with locally advanced Human papillomavirus (HPV) 16-positive cervical cancer.


METHODS
From 102 patients treated at our institutes, 38 patients with histologically-proven HPV16-positive cervical cancer were included in this prospective case-controlled study. All patients underwent exclusive radiotherapy-only. Complete response was defined as an absence of residual disease at clinical examination and radiological imaging, three months after the completion of treatment. Gene expression levels, assessed before radiotherapy, were compared between responders and non-responders. Controls consisted of normal cervical tissue samples from 30 patients with non-oncological indications.


RESULTS
Twenty patients (52.6%) showed a complete response. Gene expressions of IGF1R (34%), IGF2 (24%), and GAPDH (median=3.26 versus 2.12) were increased in cancer patients, in comparison with the control group. Higher levels of expression of GAPDH were observed in patients co-expressing IGF2 and IGF1R, who had a hemoglobin level ≤ 11 g/dl (p=0.05). Clinical characteristics in the responder and in the non-responder groups were similar. In bi-variate and multi-variate analyses, IGF1R expression was the only factor predictive of response to radiotherapy (p=0.018). Accordingly, patients with IGF1R expression had a 28.6-fold greater risk of treatment failure.


CONCLUSIONS
In our study, IGF1R was a strong predictive marker of lack of response to radiotherapy. Larger prospective trials are needed to validate IGF1R as a biomarker of radiation response for patients with HPV16-positive cervical cancer.
Research on Cancer Biology, National Cancer Institute, Bogotá, Colombia. pmoreno@cancer.gov.co
Pablo
P
Moreno-Acosta
Oscar
O
Gamboa
Myriam
M
Sanchez de Gomez
Ricardo
R
Cendales
German Dario
GD
Diaz
Alfredo
A
Romero
Joseph
J
Balart Serra
Zoila
Z
Conrado
Antonin
A
Levy
Cyrus
C
Chargari
Nicolas
N
Magné
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D015870:Gene Expression; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000096:biosynthesis; D006454:Hemoglobins / Q000032:analysis; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000532:radiotherapy*; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D059467:Transcriptome; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
D014408:Biomarkers, Tumor; D006454:Hemoglobins; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D017526:Receptor, IGF Type 1