Esophageal cancer is the sixth most deadly tumor in the world. Although the current treatment methods are constantly improving, the 5-year survival rate of patients is still poor, and postoperative recurrence is the most important factor for the poor prognosis of patients. Therefore, this study aims to explore whether FPR can early predict postoperative recurrence in patients and its prognostic significance for OS and RFS. FPR is the ratio of fibrinogen to platelets, which is more convenient to calculate and can be used to predict the prognosis of gastric cancer. In this study, we combined fibrinogen and platelets, taking the ratio, to explore the predictive significance of postoperative ESCC recurrence, as well as the predictive significance of OS and RFS. We have shown through research that FPR is a good predictor of postoperative ESCC recurrence. Previous studies have shown that fibrinogen has predictive significance for postoperative ESCC metastasis. On this basis, we have studied the predictive value of FPR for ESCC postoperative recurrence. Through our data analysis, FPR has a greater predictive value for postoperative recurrence than any single factor of fibrinogen and platelets. And it shows that FPR is an independent prognostic factor of OS and RFS, while fibrinogen and platelets are not. This study also established a nomogram to predict the disease-free survival of 3, 5 years and 3, 5 years of overall survival after radical esophagectomy for esophageal cancer, and it can be seen that the calibration curve and the simulation curve fit well.
There has been no research on FPR in esophageal squamous cell carcinoma. We know a lot of research on platelets and fibrinogen in tumor metastasis. Tumor metastasis is a multi-system regulation process, in which the blood vasculature plays an important role. Tumor cells fall off from the original site, enter the whole body through the circulatory system, and eventually colonize the target organs, resulting in tumor metastasis. Circulating tumor cells adhere to platelets, leukocytes and endothelial cells to make tumor cells exudate from the vasculature and promote tumor cells to colonize and survive far away . Fibrinogen and platelets are linked to each other and jointly promote the development of tumors. Fibrinogen can promote the adhesion of platelets to tumor cells, and platelets form thrombin so that fibrinogen accumulates around tumor cells, thereby protecting tumor cells from natural killer cytotoxicity . What mechanism does fibrinogen mainly promote tumor progression and metastasis? A lot of research is needed in the future. At present, some studies claim that tumors may be the source of fibrinogen. Fibrinogen, fibrin and its degradation products have Pro-inflammatory activity, they indirectly stimulate the endothelium to secrete von Willebrand factor, leading to platelet activation associated with neoplastic diseases . Fibrinogen is converted into fibrin, and fibrinogen also promotes the formation of new blood vessels, so it can promote tumor growth and metastasis . Fibrinogen levels are elevated in malignant tumors such as gastric cancer, esophageal cancer, breast cancer, lung cancer, colon cancer and ovarian cancer, and high fibrinogen indicates a poor prognosis. In gastric cancer, fibrinogen is associated with disease progression and recurrence . In esophageal cancer, it has been reported that fibrinogen is related to lymph node metastasis and is a biomarker for predicting tumor progression, recurrence and prognosis of esophageal cancer . Thrombocytosis is also closely related to tumor progression. Platelets promote blood clotting associated with cancer. Platelets are recruited to cover the surface of tumor cells, thereby protecting them from immune cell responses and promoting cancer growth and metastasis . There are also reports that cancer cells migrate to the vasculature and interact with platelets, leading to platelet aggregation induced by tumor cells . This shows that tumor cells and platelets have a mutually promoting relationship. Fibrinogen and platelets are elevated in a variety of cancers, such as lung cancer, cervical cancer, stomach cancer, colon cancer, pancreatic cancer, and prostate cancer. In pancreatic cancer, fibrinogen and platelets can predict tumor metastasis .
Our research shows that FPR's AUC (0.620) is better than the other two indicators, but the AUC value is less than 0.8, which is not high enough, and more data in the future are needed for the next step of verification. The limitations of this study include that this is a retrospective study, the data comes from a single organization, the sample size of the data is small, and the sample size needs to be increased to verify the accuracy of the FPR cutoff value and its impact on the prognosis. Secondly, the risk model we evaluated also comes from a single institution, and its applicability is relatively limited, and further multi-institution research is needed. In summary, preoperative FPR is convenient, cheap, and simple to calculate. It can predict postoperative recurrence of ESCC patients better than plasma fibrinogen levels. Patients with high preoperative FPR are more likely to relapse after surgery, and have poor OS and RFS.
Potential limitations of this study include the use of a retrospective design. In order to select a more uniform patient background, we only included patients with esophageal cancer who were likely to be cured by surgery, and excluded patients with esophageal cancer who received neoadjuvant therapy, which may also limit the general application of the results of the study. In addition, larger-scale prospective studies are needed to confirm these preliminary results.