In this study, we attempted to determine preoperative indicators to stage OC to help attain ODS, reduce surgical complications and economic burden, and better evaluate the prognosis of OC patients. Multivariate logistic regression analysis showed that LMR was significantly associated with stage of OC (Table 3): the lower the LMR, the higher the stage, and the worse the prognosis, which was consistent with the conclusion of previous research . Our study also showed that serum CA125 was associated with stage of OC (Table 3); however, the specificity was lower than LMR (Figs. 1a, 1b). To better analyze the factors associated with OC staging, we recommended COLC to improve the accuracy, which achieved a higher AUC and specificity than LMR or CA125, indicating that COLC might have a higher specificity associated with OC staging.
Our study also showed that ascites was associated with stage of OC (Table 3), one probable mechanisms is that constitutive expression of STAT3 in malignant ascites plays a role in ovarian tumor progression and metastasis. Besides, Matt et al (2019) showed that ascites might be associated with CA125 by regulating MUC16 expression at a posttranscriptional level through an Akt-dependent pathway, accordingly, we matched samples with presence or absence of malignant ascites, and the results showed that both LMR and CA125 were significantly associated with OC staging for presence or absence of malignant ascites (Table 4).
LMR and CA125 are calculated directly or computed from blood and can be easily measured, in addition to being practical and inexpensive metrics. At present, several studies have been conducted with respect to the application of LMR and CA125 in OC. LMR and CA125 could likely serve as clinically useful indicators of metastasis and survival in OC patients [4, 7, 12]. CA125 also was reported as a risk factor in the diagnosis of OC . However, few studies have been conducted with respect to the magnitude of LMR an CA125 on staging OC. Our study preliminarily showed that LMR, CA125, and COLC might be risk factors for OC staging.
The mechanisms underlying the capacity of LMR in OC have not yet been elaborated. We tried to explain the possible mechanisms. First, the association between lymphocytes and malignancies has been well established. Tumor infiltrating lymphocytes in OC can prevent cancer cells from spreading and metastasis by establishing a defense barrier . The decrease of peripheral blood lymphocyte count may lead to weak and insufficient tumor immune response, thereby promoting tumor progression and metastasis  and resulting in rapid disease progression and late surgical pathological stage in OC patients. Second, inflammation can make monocytes migrate from the bone marrow into peripheral blood . After being recruited into tumor tissue, monocytes can differentiate into tumor-associated macrophages (TAMs) . TAMs can not only play an immunosuppressive role in a variety of tumor microenvironments, including OC, but can also promote tumor cell infiltration, growth and neovascularization, and metastasis [17, 18]. Therefore, to an extent, peripheral blood mononuclear cell counts can reflect the formation or existence of TAMs. Besides, the LMR often represents the relative decrease of lymphocyte count and (or) the relative increase of monocyte count, which can reflect the balance of anti-tumor immunity and pro-tumor inflammatory response : low-level LMR often represents the dominant role of pro-tumor inflammatory response, indicating a high level of malignancy and rapid progress in OC. Further, in this case, the possibility of advanced stage OC that is difficult to treat with relatively poor prognosis is higher; on the contrary, high-level LMR indicates that the anti-tumor immune system of patients with OC is more active, indicating that the disease progression of OC is slow, with the possibility of early stage OC and relatively better prognosis.
Rising and falling levels of serum CA125 correlate with the progression and regression of high-grade serous ovarian carcinomas , making CA125 a possible factor for OC staging. However, some researchers have also suggested that because of its low specificity and the observed increased levels in different physiological situations, CA125 is not considered as a very good differentiating biomarker for ovarian tumors . Therefore, we recommended the combination of CA125 and LMR (COLC) to stage OC. Our results showed that the AUC and specificity of COLC were higher than those of LMR or CA125 to stage OC (Fig. 1), implying that COLC might improve the accuracy in staging OC and provide guidelines for selection of treatment. As a new biomarker, COLC might play a role in immune surveillance and provide novel approaches and strategies for treatment of OC.
To our knowledge, this is the first study to evaluate the relationship among LMR, CA125, COLC, and stage of OC. However, our study also has some limitations. Firstly, the retrospective design meant that we cannot conclusively state that LMR, CA125, and COLC are risk factors for advanced stage of OC. However, our study provides a potential clinical strategy for staging advanced OC. Secondly, the potential bias in testing serum CA125 and peripheral blood level cannot be completely eliminated. Nonetheless, we believe that the influence of LMR and CA125 level on the risk of advanced stage of OC will be of interest to clinicians to improve the accuracy in preoperative staging and make clinical strategies. Moreover, LMR is an inflammatory marker that could be affected by autoimmune status and other diseases; hence, we allowed a 30-min interval for blood collection to exclude any possible treatment or drug interference in the results.