Abstract:

Objective To investigate the diagnostic value of cervical cell DNA ploidy analysis combined with negative costimulatory molecule B7 homolog 4 （B7-H4） and protein kinase Cδ （PKCδ） for cervical cancer. Methods A total of 160 cervical cancer patients diagnosed and treated at Shijiazhuang People's Hospital from January 2018 to January 2022 were selected as the cervical cancer group. Meantime， 160 women who were screened for cervical cancer in our hospital during this period were selected as the control group. According to the examination results， they were divided into normal or inflammatory group （n=52）， low-grade cervical intraepithelial neoplasia （CIN） group （n=68） and high-grade CIN group （n=40）. The automatic cell image analysis system was used to analyze the DNA ploidy of cervical cells. The levels of B7-H4 and PKCδ in serum were determined by enzyme-linked immunosorbent assay. Pearson method was used to analyze the correlation between serum B7-H4 and PKCδ; the diagnostic value of cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ in cervical cancer was evaluated by the receiver operator characteristic （ROC） curve; multivariate logistic regression was used to analyze the risk factors of cervical cancer. Results The numbers of DNA ploidy positive cases of cervical cells in normal or inflammatory group， low-grade CIN group， high-grade CIN group and cervical cancer group were 16 （30.8%）， 27 （39.7%）， 26 （65.0%） and 127 （79.4%）， respectively， with a statistically significant difference （H=55.86， P<0.001）. Further pin-by-pair comparison showed that compared with normal or inflammatory groups， the proportion of DNA ploidy positive in high-grade CIN group and cervical cancer group were higher （both P<0.05）. The proportion of DNA ploidy positive in cervical cancer group was higher than that in low-grade CIN group （P<0.05）. Serum B7-H4 levels in normal or inflammatory group， low-grade CIN group， high-grade CIN group and cervical cancer group were （57.21±10.21）， （79.17±11.34）， （92.73±15.36）， （126.56±20.25） ng/ml， respectively， with a statistically significant difference （F=285.45， P<0.001）. Serum PKCδ levels were （89.34±18.29）， （71.79±15.82）， （53.39±11.84）， （40.23±10.21） ng/ml， respectively， with a statistically significant difference （F=216.28， P<0.001）. Further pin-by-pair comparison showed that serum B7-H4 levels in normal or inflammatory groups， low-grade CIN group， high-grade CIN group and cervical cancer group increased in turn （all P<0.05）. Serum PKCδ levels in normal or inflammatory groups， high-grade CIN group and cervical cancer group were decreased in turn （all P<0.05）. Pearson correlation analysis showed that the serum B7-H4 and PKCδ levels in patients with cervical cancer were negatively correlated （r=-0.47， P<0.001）. ROC curve analysis showed that the area under the curve （AUC） of cervical cell DNA ploidy for cervical cancer diagnosis was 0.82 （95%CI： 0.78-0.86）， and the sensitivity and specificity were 83.9% and 79.9%， respectively. The AUC of serum B7-H4 in the diagnosis of cervical cancer was 0.92 （95%CI： 0.89-0.95）， the sensitivity and specificity were 95.7% and 76.1%， respectively， and the cutoff value was 111.12 ng/ml. The AUC of serum PKCδ for diagnosis of cervical cancer was 0.92 （95%CI： 0.89-0.95）， the sensitivity and specificity were 85.6% and 88.9%， respectively， and the cut-off value was 54.83 ng/ml. The AUC of the combined diagnosis of cervical cancer was 0.99 （95%CI： 0.97-0.99）， and the sensitivity and specificity were 98.3% and 75.9%， respectively. The AUC of the combined diagnosis of cervical cancer was higher than that of DNA ploidy （Z=8.00， P<0.001）， serum B7-H4 （Z=4.34， P<0.001）， and serum PKCδ （Z=4.61， P<0.001） alone. Multivariate logistic regression analysis showed that high level of B7-H4 in serum （OR=2.94，95%CI： 1.78-4.84， P<0.001）， low level of PKCδ （OR=4.33，95%CI： 1.88-10.00， P=0.001） and positive DNA ploidy in cervical cells （OR=5.77，95%CI： 2.38-13.99， P<0.001） were independent risk factors for cervical cancer. Conclusion The positive proportion of DNA ploidy in cervical cells of patients with cervical cancer is increased， the serum B7-H4 level is increased， the PKCδ level is decreased， and cervical cell DNA ploidy analysis combined with serum B7-H4 and PKCδ has a high diagnostic value for cervical cancer.

Key words: Uterine cervical neoplasms, Protein kinase C-delta, Early diagnosis, Cervical cell DNA ploidy, Negative costimulatory molecule B7 homolog 4