The etiological diagnosis of pleural effusion is a clinical problem, and the traditional methods have been proved to be insufficient [15, 16]. Traditional pleural fluid cytology has been used to detect tumor cells in pleural fluid. However, sensitivity varies from 30–60% and the additional sensitivity provided by blindly obtained pleural needle biopsy specimens is minimal [17]. Although thoracoscopy is more sensitive to malignant cases, they are expensive and not available in all medical centres [18]. In recent years, with the development of tumor molecular biology, tumor markers have been widely used in the diagnosis of pleural effusion. We investigated TuM2-PK in the serum and pleural effusion of patients with pleural effusion caused by benign disease or lung cancer.
PK has four isozymes: L-type, R-type, M1 type and M2 type. M2 type is mainly expressed in lung, distal convoluted tubules of normal kidney, embryo and or proliferative tissues. There are many reasons for the abnormal expression of TuM2-PK in malignant tumors. It has been confirmed that, on the one hand, due to the phosphorylation of M2-PK tyrosine site, the tetramer is dissociated into dimer, and M2-PK is preferentially expressed in tumor cells in the form of dimer with low affinity for phosphorylated pyruvate. TuM2-PK has very low affinity for phosphoenolpyruvate, resulting in the accumulation of phosphoenols and significantly reducing the degradation of fructose 1, 6-diphosphate to pyruvate, And DNA synthesis increased. In addition, abnormal energy metabolism in malignant tumors is also one of the main reasons for the increase of TuM2-PK. Previous studies have shown that TuM2-PK can be detected in body fluids, which may be due to the release of TuM2-PK during tumor necrosis or metastasis [19]. It has been reported that TuM2-PK was significantly increased in MPE, which can be used as an index to distinguish BPE and MPE [20]. The results showed that the levels of TuM2-PK in pleural effusion and serum of patients with MPE were significantly higher than those of patients with BPE, and increased most significantly in SCLC, which was significantly higher than those of lung ADC and SCC, while the levels of TuM2-PK in pleural effusion and serum of patients with ADC were also higher than those of patients with SCC, Therefore, TuM2-PK plays a certain role in the typing and diagnosis of lung cancer. We found that the expression level of TuM2-PK in pleural effusion of patients with MPE was significantly higher than that in serum. Therefore, it is considered that TuM2-PK plays an important role in the accumulation of pleural effusion. Detection of TuM2-PK level is important for differential diagnosis of BPE and MPE.
CEA is a glycoprotein, which mainly exists in the intestine, liver and pancreas of the fetus before 6 months of pregnancy. Due to the large molecular weight of CEA, it synthesized and released by pleural metastasis to pleural effusion is not easy to enter human blood circulation, so it rises earlier in pleural effusion and its level is also significantly higher than that in serum. CEA has been widely used in the diagnosis of a variety of tumors. The concentration of CEA increases in the serum of 30% ~ 80% of lung cancer patients. The degree of increase is directly related to the number of cancer cells, and the positive rate for the diagnosis of lung ADC is the highest [21]. The results also confirmed that the CEA concentration and positive rate of lung ADC were significantly higher than those of SCC and SCLC, which was consistent with the literature report. There are also many reports on the use of CEA in the differential diagnosis of pleural effusion [22, 23]. The results of this study demonstrated that the CEA levels of serum and pleural effusion in MPE were significantly higher than those in BPE, which was basically consistent with the report [10–14].
We detected TuM2-PK and CEA in serum and pleural effusion of patients with MPE alone and in combination. It was found that the sensitivity and specificity of a single detection index in the diagnosis of MPE were less than 80%. Combined detection could increase the sensitivity and specificity. Therefore, the combined detection of TuM2-PK and CEA in serum and pleural effusion is helpful to the differential diagnosis of MPE and BPE, and combined detection is helpful to the pathological classification and clinical diagnosis of pleural effusion.
Our findings demonstrate that determining serum and pleural effusion levels of the markers TuM2-PK and CEA is useful in differentiating between MPE and BPE. In comparison with either single determination of concentration in serum or pleural effusion, the combined detection of two markers was important in the diagnosis of lung cancer. In clinical practice, when the cytopathological examination of pleural effusion is negative, the simultaneous detection of TuM2-PK and CEA levels in serum and pleural effusion may help clinicians decide whether to obtain cytological or histological specimens by invasive methods to investigate the possible diagnosis of malignant tumors.