Although the current pathological diagnosis of gliomas grading was the gold standard, it needed to be confirmed after surgery. For the diagnosis of HGGs grading, we need a method of preoperative prediction to guide surgical strategies and treatment more accurately. Previous studies had indicated that inflammation, including NLR, PLR, LMR, FIB, ALB, AGR and PNI had the predictive and diagnostic value for the grading and prognosis of gliomas8, 10–12. Our research mainly analyzed the diagnostic value of preoperative hematological indicators related to inflammation, coagulation and nutrition in the classification and IDH molecular subtypes of HGGs. In addition, we explored their correlation with age, gender, pEPI, pKPS in different grade of HGGs. Furthermore, we evaluated their levels in IDH molecular subtypes of HGGs and different grade of HGGs.
The results of this study showed that the higher grade gliomas had higher levels of NLR, MLR, FIB, ALB and GLOB, and lower levels of PLR, AGR and PNI, respectively, This result was consistent with the previous related studies11, 13, and declared more severe inflammation and worse nutritional status were present in higher grade gliomas. However, they were not statistically significant in the different grade of HGGs except FIB, which was contrary to these researches11, 13. The possible reason for this was that there were too few G3 gliomas included in this study. Only the levels of NLR and FIB were associated with IDH mutation groups, indicating that there was a link between inflammation and coagulation14. Furthermore, we further analyzed the relationship between hematological indicators and IDH mutation subgroups, and found that only FIB had a significant difference between G4 IDH-wt and G3 IDH-mut or G4 IDH-mut. Previous study had shown that the immune response of the tumor microenvironment was more susceptible to the modulation of IDH mutation status in lower-grade gliomas15. This result suggested that there may be a connection between systemic and local inflammation and coagulation and immune regulation.
In our study, the levels of FIB and GLOB were positively correlated with age, and the levels of ALB, AGR and PNI were negatively correlated in the HGGs classification. However, the inflammation indicators were oppositely correlated in the HGGs grading groups. The reason for this result was the levels of FIB may reflect the critical function of FIB in an inflammatory tumor microenvironment that favors tumor progression6. When comparing hematological indicators in gender, we found that NLR and FIB had higher levels in men. Moreover, the level of PNI had the same result, consistent with the previous study16. Different from other research results13, 17, the levels of PLR in our research were opposite in this comparison. There was no significant difference in the levels of hematological indicators in the pKPS and pEPI subgroups.
In the analysis of the diagnostic value of hematological indicators, single and combined indicators were explored, respectively. The level of FIB had the highest diagnostic value among the 8 hematological indicators in distinguishing GBM and G4 IDH-wt from HGGs. Our results were different from studies that found that NLR was the best diagnostic indicator, and they studied the ability of hematological indicators in distinguish GBM and G4 IDH-wt from different diseases and three grade of gliomas11, 13. In addition, as for combined indicators, age + PNI had the highest diagnostic value in the research of Wang et el13, however, the best combined diagnostic index was NLR + MLR in the study of Zheng et el11. The difference from them was that our research distinguished GBM and G4 IDH-wt from HGGs, and age + FIB had the highest diagnostic value among all the combined indicators. It was worth noting that grade Ⅰ and grade Ⅱ gliomas were included in their study, respectively.
This mechanism was temporarily unclear between hematological indicators and the grade of gliomas. Previous studies had declared that immune suppression induced by neutrophils may promote the progression of glioma, and some T lymphocyte subsets may inhibit it by inducing cytotoxic cell death and cytokine production18, 19. Shao et el confirmed that platelet activation contributes to tumor angiogenesis, destroys extracellular matrix and releases adhesion molecules to promote cancer cell proliferation and metastasis, thus proving the importance of platelet activation in tumorigenesis20. The correlation between nutritional indicators and cancer may be related to the antioxidant effect of albumin on carcinogens such as nitrosamines and aflatoxins, and the levels of GLOB may be related to the progression and metastasis of certain cancers21, 22. Moreover, albumin reflected the state of systemic inflammation by down-regulating tumor necrosis factor alpha and interleukin 623. Plasma fibrinogen was an important factor in inflammation and cancer expression, and had been demonstrated in vitro studies playing an important role in tumor cell proliferation, epithelial-mesenchymal transition, invasion, angiogenesis and hematological dissemination of tumor cells24–26.
Our current research has some limitations. Firstly, this study may have a selection bias because it is a single center and retrospective analysis. Secondly, the sample size of the study included in this study was small, especially G3 gliomas, and grade Ⅰ and grade Ⅱ gliomas were not included. In addition, we did not have data for O6-methylguanine-DNA methyltransferase (MGMT) methylation status and telomerase reverse transcriptase (TERT) promoter status, both of which play an important role in patients with gliomas27. Therefore, multi-center prospective studies, further molecular pathology experimental analyses, large sample researches of HGGs are required.