Abstract
While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia.
Highlights
While the mortality rates of cervical cancer have been drastically reduced since the introduction of the Pap smear test, it remains one of the leading causes of death in women worldwide [1]
GSE63514 was from the Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED study), and it contained 128 samples [1]
Capture Microdissection System was used to capture the epithelial lining of the cervix from normal healthy control specimens or precancerous and invasive cancerous cell masses from cervical lesions
Summary
While the mortality rates of cervical cancer have been drastically reduced since the introduction of the Pap smear test, it remains one of the leading causes of death in women worldwide [1]. Intracellular entropy can predict the development of cervical intraepithelial neoplasia resulting in progression of the lesion to cervical dysplasia, carcinoma in situ and invasive cancer. Cervical lesions are classified into cervical intraepithelial neoplasia (CIN) 1, 2 and 3 based on its relationship with the prognosis. CIN 3 includes severe dysplasia and carcinoma in situ, and management involves treatment because it is highly likely to develop into invasive cancer. Conization, which is one of the most common treatments for cervical lesions, increases the risks of postoperative complications and pregnancy complications, such as abortion and preterm labor [4, 5]. The treatment decision should be carefully made On this topic, many studies have been performed to appropriately evaluate the risk of developing cervical lesions [2, 3, 6]. Detection of high-risk HPV has a high negative predictive value, its positive predictive value should be discussed because of the aforementioned transient infection
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