Compared with non metastatic tumor cells, TTR is highly expressed in metastatic tumor cells and is considered to cause metastasis by regulating the transport of tumor cells, resulting in poor prognosis [17]. However, the role of TTR in the occurrence and development of lung cancer is not clear. Therefore, we investigated the expression of TTR in lung cancer and its relationship with clinicopathology. Our study showed that the TTR level in cancer tissues was significantly higher than that in paracancerous lung tissues. In addition, we also found that the expression of TTR was related to TNM stage and lymph node metastasis, suggesting that TTR was involved in the occurrence and development of tumor. In prostate cancer, overexpression of TTR was found to be related to tumor grade and stage [18]. Kaplan Meier analysis further showed that OS and DFS in patients with high TTR were significantly longer than those in patients with low TTR. This is consistent with the previous results that the abnormal expression of TTR is associated with poor clinical prognosis in lung cancer and gastrointestinal cancers [19, 20]. Meanwhile, subgroup analysis showed that in patients with stage I and II lung cancer, OS and DFS of patients with high TTR were significantly longer than those with low TTR, indicating that TTR also has a value prognosis for early lung cancer.
At present, the prognosis of lung cancer depends on TNM stage. However, TNM stage is not always able to predict the prognosis of patients, so there is an urgent need for other clinical prognostic indicators to assist and supplement TNM stage. In addition, the identification of new biomarkers predicting the prognosis of lung cancer patients is helpful to the selection of treatment options and the improvement of survival rate. This study showed that the low expression of TTR in lung cancer is related to the poor prognosis of lung cancer. Univariate and multivariate Cox proportional hazards regression analysis further showed that expression of TTR was an independent risk factor for poor prognosis in patients with lung cancer. Therefore, TTR can be used as a new prognostic index of lung cancer.
After analyzing the serum of the patients with pancreatic cancer and the normal control group by the surface-enhanced laser desorption-ionization time of flight mass spectrometry analysis, it was found that the serum TTR level of the patients with pancreatic cancer was significantly lower than that of the normal control group [21]. The expression of TTR in the serum of patients with lung cancer was significantly lower than that of healthy controls, but higher than that of patients with benign lung diseases. The TTR level measured by enzyme-linked immunosorbent assay and surface-enhanced laser desorption ionization analysis was consistent with the previous results [22]. In this study, the results showed that the serum TTR level of lung cancer patients was lower than that of the controls, and the higher the stage, the lower the level. In addition, we also investigated the relationship between circulating TTR and tissue expression in tumor samples. We found that the expression of TTR was positively correlated with the level of serum TTR, indicating that serum TTR originated partially from tumor cells.
It is reported that TTR plays a role of tumor inhibitor in the occurrence and development of malignant tumors, but its mechanism in the occurrence and development of malignant tumors is not clear [23, 24]. Considering that TTR may affect the activity of the rate limiting enzyme indoleamine 2, 3-dioxygenase. It can consume tryptophan to produce kynurenine after enhancement, and kynurenine inhibits T cell activity, so as to produce immune tolerance and promote the occurrence and development of tumors [25].