Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1451
Peer-review started: January 26, 2018
First decision: February 10, 2018
Revised: March 7, 2018
Accepted: March 10, 2018
Article in press: March 10, 2018
Published online: April 7, 2018
Gallbladder cancer is a rare hepatobiliary tumor with a relatively low incidence. Due to the lack of significant specific symptoms at the early stage, the prognosis of gallbladder cancer is poor and can be fatal. Therefore, determining a convenient and cost-effective prognostic biomarker is urgently required for patients with gallbladder cancer. Elevated fibrinogen has been demonstrated to be associated with poor prognosis in multiple malignancies, while CA199 is considered a widely accepted diagnostic and prognostic marker of gallbladder cancer. There have been very few studies on the role of fibrinogen in the prognosis of patients with gallbladder cancer. To date, studies on the combined use of fibrinogen and CA199 to predict the prognosis of patients with gallbladder cancer have not been conducted. The combined use of fibrinogen and CA199 avoids inconsistencies caused by the use of a single indicator and enhances predictive efficacy.
The main aim of this study was to validate and identify a convenient and inexpensive combination of biomarkers with a higher prognostic value for patients with gallbladder cancer. From our research, we found that the combination of preoperative plasma fibrinogen and CA199 was a more efficient prognostic factor than either parameter alone in patients with gallbladder cancer. Due to this finding, we can screen potential high-risk candidates for gallbladder cancer and provide prognostic guidance for surgical patients with gallbladder cancer. In addition, this study also provides clinical evidence and preconditions for the future study of how fibrinogen promotes the proliferation and metastasis of malignant tumor cells.
The main objective of this study was to identify a convenient and more efficient prognostic biomarker for gallbladder cancer patients. From this study, we found that both elevated fibrinogen and elevated CA199 were independent risk factors for gallbladder cancer patients. Furthermore, the combination of preoperative plasma fibrinogen and CA199 was a more efficient prognostic factor than either parameter alone in patients with gallbladder cancer. These findings not only provide a further example which proves the relationship between hemostasis and tumor, but also provide powerful clinical evidence for related basic research in the future.
We used an Excel table to organize research-related clinical data, and imported these variables into SPSS 24.0 statistical software. We then assigned the different types of variables appropriately. We determined the optimal cut-off values for fibrinogen and CA199 by plotting ROC curves, and then determined the association of fibrinogen and CA199 with other clinicopathological variables using the R × C table. Finally, univariate and multivariate analyses were performed to determine the independent prognostic factors in patients with gallbladder cancer.
Given the different HRs of the two parameters (CA199: 1.842, plasma fibrinogen: 1.711), one methodological innovation of this study was that we assigned different scores to elevated plasma fibrinogen levels and elevated CA199 levels, instead of assigning the same score as in the previous scoring system. This scoring approach further differentiates the difference in the prognostic efficiency between plasma fibrinogen and CA199, rather than simply assigning each parameter with 1 point. Based on the overall survival curve (Figure 3) and the ROC curve (Figure 4) in the text, we observed that the new scoring system effectively improved the prognostic accuracy of the biomarkers.
Our study demonstrated that the best cut-off values for pretreatment fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively, in patients with gallbladder cancer. After single factor and multivariate analysis, it was shown that elevated pretreatment fibrinogen, elevated pretreatment CA199, resection margin and TNM stage were independent risk factors for gallbladder cancer patients. When the elevated pretreatment fibrinogen and elevated pretreatment CA199 were combined with different assigned scores according to their different HRs, the prognostic accuracy and power was significantly improved (the AUROC increased to 0.765, a relatively high value). These research findings confirm the relationship between hemostatic factors and cancer, in this case gallbladder cancer. How does the hemostatic factor fibrinogen influence the development, growth, and metastasis of gallbladder cancer cells? The underlying mechanism is still unknown, and further studies are required to identify and confirm the mechanism involved.
In the present study, we found that the combination of preoperative plasma fibrinogen and CA199 is a more efficient prognostic factor than either parameter alone in patients with gallbladder cancer. We proposed that the combination of hemostatic factor and specific oncology markers can better predict the prognosis of gallbladder cancer, as hemostatic and oncology markers can compensate for each other’s inconsistency in predicting tumor prognosis and thus enhance overall prognostic efficacy. Fibrinogen is associated with the development, growth, and metastasis of cancer cells, and CA199 is a product of tumor cell growth and metabolism. However, from our study findings, we observed that they had different prognostic efficacy (as they had different HRs) in gallbladder cancer patients; therefore, we assigned different scores to them which differed from the previous traditional scoring system. Using this new method, the prognostic efficacy of these two prognostic biomarkers combined was significantly improved, and this combination was used to screen potential high-risk gallbladder cancer candidates, identify appropriate surgical patients, and adopt the best follow-up strategy.
In this study, we found that the combination of a hemostatic factor and oncology factor could compensate for each other’s inconsistency in predicting tumor prognosis and improve the overall prognostic efficacy. The combination of these factors was more efficient than either parameter alone in predicting the prognosis of gallbladder cancer patients. These factors are inexpensive, easy-to-use and highly accurate for determining the prognosis of gallbladder cancer patients. Further large-scale, well-designed and prospective studies to verify the findings and conclusions of this investigation are required.