Combined use of CA125, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for the diagnosis of borderline and malignant epithelial ovarian tumors

CA125, NLR and PLR showed significant differences among benign, borderline and malignant EOTs

A total of 284 patients were included in this study. The basic laboratory parameters of all included patients were briefly presented in Table 1. The mean ages of the patients diagnosed as benign, borderline and malignant EOTs were (48.33 ± 15.84), (47.77 ± 18.88) and (47.6 ± 20.62) years, respectively (P = 0.629). As shown in Table 1, the expression of CA125 showed significant differences among benign, borderline and malignant EOTs (P < 0.001). In addition, it was apparent that inflammatory biomarkers such as neutrophil (N), PLR, NLR and monocyte/lymphocyte ratio (MLR) showed an upward trend from benign to borderline and malignant EOTs (P < 0.001), while lymphocyte (L) showed the opposite trend (P < 0.001), suggesting that they have certain diagnostic value for benign, borderline and malignant EOTs.

Table 1 Laboratory parameters of participants with EOTs

Compared with N, L and platelet (PLT), NLR and PLR provided a more comprehensive reflection of the inflammatory response and showed a significant gradient change, and were selected along with CA125 as indicators for follow-up studies. Considering that there was no significant difference in monocyte (Mo) among the three groups (P = 0.868), and MLR was essentially the reflection of differences in L among the three groups, thus no redundant studies were conducted on MLR. Additionally, human epididymis protein 4 (HE4) was excluded from subsequent studies because the difference of HE4 between borderline and benign EOTs was not statistically significant (P = 0.1268).

Correlation between CA125, NLR, PLR and clinic-pathological characteristics of BEOT and MEOT patients

We further analyzed the correlation between CA125, NLR, PLR and clinic-pathological characteristics of MEOT patients. The results were shown in Table 2. Advanced MEOT (Stage III-IV) group tended to have higher CA125, NLR and PLR than early stage MEOT (Stage I-II) group. Moreover, CA125, NLR and PLR were higher in the lymph node metastasis MEOT group compared with the non-lymph node metastasis MEOT group. However, there were no statistically significant differences in CA125, NLR and PLR among different ages, histological grades and pathological types. These results suggested that higher preoperative CA125, NLR and PLR levels predict a higher probability of advanced MEOT progression and lymph node metastasis. Additionally, we also explored the levels of inflammatory and tumor biomarkers in serous and mucous BEOTs, and no statistically significant differences were found between the two groups (Supplementary data 1).

Table 2 Relationship between laboratory parameters and clinic-pathological characteristics of MEOT patientsEfficiency of single use of CA125, NLR and PLR in diagnosing benign, borderline and malignant EOTs

According to the association of CA125, NLR and PLR with EOTs, ROC curves were made and used to determine the optimal cut-off value and the corresponding sensitivity and specificity (Fig. 1A, B, C). The results were shown in Table 3. The cut-off value of CA125 in distinguishing benign and malignant EOTs was selected according to the commonly used clinical value, namely CA125 = 35 U/ml. When Youden Index reached the maximum, the optimal cut-off values of NLR and PLR for distinguishing benign and malignant EOTs were 1.76 and 114.3. The corresponding sensitivity were 70.31, 79.69 and 84.38%, and the corresponding specificity were 100, 90.97 and 92.9%, respectively. When it came to identify benign and borderline EOTs, the optimal cut-off values of CA125, NLR and PLR were 18.72, 1.244 and 89, respectively. The corresponding sensitivity were 53.97, 87.5 and 92.06%, and the corresponding specificity were 100, 69.87 and 75.48%, respectively. Apart from this, when differentiating borderline and malignant EOTs, the optimal cut-off values of CA125, NLR and PLR were 42.74, 2.687 and 213.6, respectively. The corresponding sensitivity were 67.19, 46.88 and 34.85%, and the corresponding specificity were 77.78, 85.71 and 93.75%, respectively.

Fig. 1figure 1

ROC curves of CA125, NLR and PLR in the diagnosis of benign, borderline and malignant EOTs. A benign vs. malignant B benign vs. borderline. C borderline vs. malignant

Table 3 Cut-off value and diagnostic value of CA125, NLR and PLR in the diagnosis of EOTs

In general, CA125, NLR and PLR could be used to predict and differentiate benign, borderline and malignant EOTs, especially in the differentiation between benign and malignant tumors. However, the ability to simultaneously ensure both sensitivity and specificity in identifying BEOTs was not ideal.

Efficiency of CA125 combined with NLR and/or PLR in diagnosing benign, borderline and malignant EOTs

By constructing multiple Logistic regression model, the diagnostic system of CA125 combined with NLR and/or PLR was evaluated in Table 4. Figure 2A showed the ROC curves of CA125 combined with NLR and/or PLR to identify benign and malignant EOTs. The sensitivity and specificity of CA125 combined with NLR to differentiate benign from malignant EOTs were 90.63 and 99.35%, respectively, while that of CA125 combined with PLR were 90.63 and 98.71%, respectively. In addition, when combining three indicators to identify benign and malignant EOTs, the sensitivity and specificity were 93.75 and 96.77%, respectively. Figure 2B showed the ROC curves of CA125 combined with NLR and/or PLR to identify benign and borderline EOTs. The sensitivity and specificity of CA125 combined with NLR to differentiate benign from borderline EOTs were 71.43 and 93.55%, respectively, while that of CA125 combined with PLR were 80.95 and 91.61%, respectively. In addition, the sensitivity and specificity of the three indicators combined to identify benign and borderline EOTs were 85.71 and 90.97%, respectively. The ROC curves of CA125 combined with NLR and/or PLR to discriminate between borderline and malignant EOTs were shown in Fig. 2C. The sensitivity and specificity of CA125 combined with NLR were 70.31 and 79.37%, respectively, and that of CA125 combined with PLR were 73.44 and 73.02%, respectively. Additionally, the sensitivity and specificity of the three indicators combined were 78.13 and 68.25%, respectively. Overall, CA125 combined with NLR and/or PLR made up for the shortcomings of single use, especially in the identification of BEOTs, ensuring high sensitivity and specificity. According to the sensitivity and specificity as well as differences in AUC, the combination of CA125, NLR and PLR had better application value than CA125 combined with NLR or PLR (Table 4), and was further superior to the application of CA125, NLR and PLR alone (Supplementary data 2).

Table 4 Diagnostic value of CA125 combined with NLR and/or PLR in the diagnosis of EOTsFig. 2figure 2

ROC curves of CA125 combined with NLR and/or PLR in the diagnosis of benign, borderline and malignant EOTs. A benign vs. malignant benign vs. borderline. C borderline vs. malignant

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