Predict the Progression of Cervical Intraepithelial Neoplasia by a Novel Marker Folate Combine with FR alpha, p16 and Ki-67

Purpose: To study the expression of serum folate and red blood cell (RBC) folate, folate receptor alpha (FR alpha), p(16INK4a) (p16), and Ki-67 at different levels of cervical intraepithelial neoplasia (CIN) and then analyze their role in the progression of CIN and their value as an early warning indicator of CIN progression. Patients and methods: We randomly collected the data of patients at the Department of Gynecology in Guangxi Medical University Affiliated Cancer Hospital from January 2016 to December 2018: Normal controls (149 cases), CIN1 (150 cases), CIN2 (100 cases), and CIN3 (101 cases). [Ethical approval by Ethics Committee of the Second Hospital of Shanxi Medical University. (2013) No. (001-1)]. The expression of serum folate and RBC folate was detected by the chemiluminescence method, while the expression of FR alpha, p16, and Ki-67 was detected by Streptavidin-Perosidase (SP) immunohistochemistry. Results: There was no statistically significant difference in serum folate levels between different grades of CIN (P=0.784), but the RBC folate levels were statistically significant (P=0.015), and there was a negative correlation between RBC folate levels and CIN lesion grades (P<0.05). The FR alpha, p16, and Ki-67 levels in the CIN group were significantly different from those in the normal control group (P <0.01), and a positive correlation was found (P <0.01); FR alpha positivity (P=0.000), Ki-67 positivity (P=0.000), and low-level RBC folate (P=0.000) were independent risk factors for the progression of CIN; these indicators were combined to establish a random forest (RF) model in which the Ki-67+FR alpha model was used as the early warning model of CIN progression. Conclusion: RBC folate, FR alpha, p16, and Ki-67 can be used as valuable clinical test indicators for predicting the progression of CIN; the combined detection model of Ki-67+FR alpha can be used as an early warning model for predicting the progression of CIN.