We observed a significant subtle positive association between PLR and the DFS of patients (synthesized HR, 1.68; 95% CI, 1.07–2.62; P = 0.023) after pooling the data with heterogeneity (I2 = 69.80%, P = 0.005), indicating that higher PLR values were likely to predict poor DFS (Fig. 2B).
It is the heterogeneity that was significantly apparent in both pooled HR of OS (I2 = 55.8%, P = 0.006) and DFS (I2 = 69.8%, P = 0.005), so we tried to identify the source of heterogeneity in the present study. The subgroup analysis was stratified to evaluate HR of OS and by region (eastern vs western), major therapy (surgery vs non-surgery), respective cut-off value (single vs multiple), sample size (large vs small), and the result of HR (positive vs negative). In multivariate analysis, meta-regression was used to explain the source of the heterogeneity, and the rest subgroup of results showed that region of publication (P = 0.687), therapeutic schedule (P = 0.853), respective cut-off value (P = 0.117), and sample size (P = 0.702) did not obviously contribute to the source of heterogeneity (Table 2). But the result of studies (positive vs negative) might partly explain the source of heterogeneity (P = 0.009). The results are the same with univariate analysis. Given the small number of studies for DFS, the meta-regression analysis was not conducted.
We removed 1 study each time to check the influence of the individual data set to the pooled HRs of OS. The combined HR and its 95% CIs were not obviously affected. The result confirmed the robustness of the outcome of this study (Fig. 3A). However, the combined HR of DFS did not show robustness of the outcome of this study after deleting 1 study each time (Fig. 3B).
A total of 7 studies reported that the correlation between the PLR and tumor differentiation, and the combined data showed that high PLR was related with poor tumor differentiation (OR, 2.12; 95% CI, 1.45–3.08; P < 0.001, Fig. 5A) with no heterogeneity. There were 6 retrieved cohorts about information on PLR and clinical stage, but the pooled estimates did not display that elevated pretreatment PLR tended to be linked with advancing clinical stage (OR, 1.29; 95% CI, 0.86–1.96; P = 0.220; Fig. 5B). The combined estimates (OR, 1.69; 95% CI, 1.20–2.39; P = 0.003; Fig. 5C) indicated that patients with higher PLR showed propensity toward depth of infiltration with no obvious heterogeneity. The synthesized data from 2 research showed that elevated PLR was associated with recurrence of CRC (HR, 2.71; 95% CI, 1.31–5.60; P = 0.005; Fig. 5D).
The systemic inflammatory response plays an important role in the progression of numerous cancers through genetic mutations, genomic instability, and epigenetic modifications, tumor metastasis, and cancer cell proliferation during different stages of tumor development.[8,36] Recent research have shown platelet secreting several angiogenic and tumor growth factors, such as vascular endothelial growth factor and platelet-derived growth factor, which might influence tumor progression, and also release microparticles that help tumor cells escape from the elimination of natural killer.[37,38] On the contrary, lymphocytes are basic components of the adaptive and innate immune system and the cellular basis of immunosurveillance and immunoediting, and CD8+ and CD4+ T-lymphocyte interaction among each other could be proven to induce tumor cell apoptosis in antitumor reaction of the immune system, which has been demonstrated to increase the survival of patients for the efficacy of chemotherapy in CRC patients.[39–41] Taken together, the relative ratio of elevated platelets and decreased lymphocytes predicts the prognosis of patients with CRC. Current opinion on the prognostic role of the PLR in CRC is inconsistent and inconclusive.
In conclusion, the pretreatment PLR is a useful factor to predict the OS in CRC and connected with clinicopathological parameters, not for DFS. These ratios may thus contribute to inform more personalized treatment decisions and predict treatment outcomes.
We acknowledge all clinical researchers of the selected studies and patients related to these studies.
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