Numerous studies have suggested that inflammatory response plays a pivotal role in development and progression of tumors [6, 23, 24]. This interaction is reportedly mediated by a series of inflammatory cells, which form major cellular components of the tumor microenvironment [25], and either directly or indirectly affect tumor cell proliferation, migration and angiogenesis by releasing various inflammatory mediators [26, 27]. Other studies have implicated peripheral blood inflammatory cell count, including neutrophils, and lymphocytes in prognosis of many tumors [28–31]. SII, a combined marker based on platelet, lymphocyte, and neutrophil counts, was first identified as an independent factor for predicting clinical outcomes of hepatocellular carcinoma patients [32]. Thereafter, its prognostic value was revealed in various tumors, including colorectal, renal cell, esophageal squamous cell, lung, prostate, and gastrointestinal cancers [33–38].
SII is a novel and convenient marker, that is easily accessible and inexpensive, and has recently been shown to be a prognostic marker for pancreatic carcinoma. In the present study, literature review-based analysis of the relationship between SII and prognosis of pancreatic carcinoma patients indicated that patients with higher SII levels have worse prognostic tendency, possibly due to several reasons. Firstly, neutrophils have been proven to promote release of a variety of inflammatory factors, such as vascular epithelial growth factor, neutrophil elastase, interleukin-8, and matrix metalloproteinase-9, which play an important role in promoting the invasion, proliferation, progression, and metastasis of cancer cells, as well as helping these cells to escape immune surveillance [39, 40]. In addition, platelets not only promote adhesion of tumor cells to microvascular endothelium, but also form a defense barrier around circulating tumor cells, helping tumor cells escape the host's immune surveillance [41]. Consequently, they directly promote tumor growth and metastasis by secreting pro-angiogenic factors and platelet-derived growth factors [42]. Conversely, lymphocytes play an important role, defending the body against cancer cells by inducing cell death, inhibiting cell proliferation and migration [5]. Therefore, a reduction in the number of lymphocytes may weaken the antitumor immune response and immune surveillance function, thereby providing a good microenvironment for tumor growth [43, 44]. Based on these mechanisms, presence of high levels of SII, platelets and neutrophils and low levels of lymphocytes, enhances tumor invasion, adhesion, progression, metastasis and weakens antitumor immune response. Thus, an elevated SII is associated with adverse clinical outcomes in tumor patients.
In the present study, we determined SII’s prognostic value in pancreatic carcinoma patients, using a total of 4 published studies comprising 1,749 patients. Pooled results indicated that pancreatic cancer patients with high levels of SII had worse OS rates than those with low SII levels. Furthermore, results from subgroup analyses, applied to explore the prognostic significance of SII in patients with different stages and treatment options, suggested that high SII levels were a potential independent poor prognostic marker for OS in patients with resectable or advanced pancreatic tumors. This trend remained, even when treatment was considered as a stratification factor, regardless of whether the patient has received surgery or mixed treatment. In addition, we also found that a high SII value was associated with CSS in patients with pancreatic tumors, although these results need further validation.
This study had several limitations. Firstly, the four included articles were retrospective cohort studies, and could have inherent defects. Secondly, the total number of included studies and the sample size was relatively small, especially for some subgroup analyses. Therefore, more large-sample studies are needed to further confirm our findings. Thirdly, we did not make stratified comparisons based on other factors, such as age, gender, and pathological type of tumor owing to the paucity of original data from individual studies. Fourthly, the optimal cut-off value of the SII was inconsistent across different studies. Finally, although the funnel plots suggested no evidence of publication bias, this may be inevitable because funnel plots lacked adequate statistical power owing to the small number of studies included. Given these several limitations, our study findings should be treated with caution.
In summary, high SII levels are associated with poor prognosis of OS and CSS in pancreatic carcinoma patients. However, SII is no significantly associated with DFS and RFS. The exact biological mechanisms underlying the observed associations are still poorly understood, although previous studies have implicated the inflammatory response pathway in their regulation. Our findings indicate that SII might be a non-invasive and valuable prognostic marker for pancreatic carcinoma for clinical practice. However, well designed, large-scale, and prospective studies are needed to validate the association between SII levels and the prognostic outcomes of pancreatic carcinoma patients.