By including 8 studies which involved 2249 participants, our results showed a significant association between higher SII and poorer OS, DFS/RFS and CSS in patients with BTC. In addition, subgroup analyses showed that a higher SII was a significant factor of poorer OS for patients with ECCA, GBC and ICCA, but not in patients with AOV Ca and mixed type ones. On stratification by treatment method, the results showed that higher SII was a significant factor of poorer OS for patients with surg and patients with mixed treatment, but not in patients with no-surg. Furthermore, higher SII predicted poorer OS in patient with BTC, regardless of cut-off values < 600 or ≥ 600, sample size < 200 or ≥ 200, analysis methods univariate or multivariate.
The prognostic effect of SII has also been studied in other cancers in meta-analysis. A recent meta-analysis—from 9 studies involving 2441 patients—showed that higher SII could predict worse survival outcomes in patients with non-small cell lung cancer. Another study also showed that higher SII was associated with poorer OS in patients with hepatocellular carcinoma. A comprehensive meta-analysis of 8 studies involving 2642 patients showed that in breast cancer patients, higher SII was associated with poorer OS and some clinicopathological factors . In our meta-analysis, the pooled results showed that higher SII was predictive of poorer OS, which is consistent with previous studies on other cancers. However, due to the lack of data, we did not analyze the correlation between SII and clinical factors in BTC patients.
Relevant studies have shown that the inflammatory cell is one of the main characteristics of tumor and plays a crucial role in tumor growth, progression, and metastasis. Moreover, deletion or inhibition of inflammatory cytokines inhibits development of experimental cancer[25, 26]. SII, as a combination of NLR and PLR, can fully reflect the balance between immunity and inflammation. High SII is caused by thrombocytopenia, neutropenia and lymphocytopenia, suggesting an increase in inflammatory state and a decrease in immune system response. Some evidence suggested that neutrophilia and thrombocythemia were associated with pro-cancer effects[27–30]. In addition to the above reasons, BTC patients with higher SII may have a poorer survival due to the micro-metastasis. Such as patients with pancreatic cancer, platelets conduce to the adhesion of tumor cells to escape host immune surveillance[31–33]. On the contrary, lymphocytes play a vital role in tumor defense. Lymphocytopenia indicates that the immune surveillance system is ineffective and has been reported to be associated with poor survival in some malignant tumors[34–36]. SII can be detected by routine blood test, and the cost is low, so it can help clinicians to predict the prognosis of patients better and easier for reasonable systematic treatment strategies.
There are also some limitations in this study. First of all, there was some heterogeneity in these included articles, and we used subgroup analysis and so on, but still failed to explore all the heterogeneity; Secondly, fewer studies were included, and fewer studies were included in subgroup analysis, which affected the accuracy of the results. Third, there was still no unified standard for the optimal demarcation value of SII, and it was easily affected by patients' own conditions, such as infection, chemotherapy and so on.
In summary, the prognostic value of SII on BTC was analyzed by meta for the first time, and current evidence suggested that SII could serve as a useful prognostic indicator in BTC. However, limited by the quantity and quality of included studies, the above conclusions need to be further verified by more high-quality studies.