Although previous studies have investigated the prognostic effects of CXCL1 expression in GC, there is no consensus in published studies due to controversial results. So we conducted the current meta-analysis to explore the prognostic impact of CXCL1 expression on GC patients. This meta-analysis is the first study to assess the prognostic and clinicopathological value of the CXCL1 in GC patients. This study demonstrated that high CXCL1 expression was significantly related to shorter OS in GC when compared with low CXCL1 expression. Further subgroup analysis revealed that elevated CXCL1 expression was found to be associated with a poor OS in Chinese and Japanese patients, but not in Finnish patients. Moreover, the stratification analysis by detection methods showed that elevated CXCL1 expression had a significantly poor OS effect on GC patients by IHC but not by RT-PCR. The meta-analysis also showed that high CXCL1 expression was related to a higher depth of tumor invasion, earlier lymph node metastasis, more advanced clinical stage and not to other clinicopathological features. Therefore, our study manifested CXCL1 expression could serve as a predictive and prognostic marker for GC patients.
A comprehensive analysis of the molecular mechanism of GC is of considerable significance to improve the early diagnosis rate and individualized treatment. Molecular mechanisms of CXCL1’s underlying the regulatory role in tumorigenesis and tumor progression have been widely researched. Numerous studies have shown that CXCL1 could promote the progression of cancer by activating multiple signaling pathways. Yang et al. revealed that high expression of CXCL1 stimulated breast cancer cell metastasis via the ERK/MMP2/9 pathway. Wang et al. discovered CXCL1 promoted breast cancer metastasis via NF-kB/SOX4 activation . Kuo et al. demonstrated CXCL1 increased cancer cell metastasis by decreasing the level of fibulin-1 expression through NF-kB/HDAC1 epigenetic regulation in prostate cancer . Wei et al. focused on the prognostic effects of CXCL1 expression in GC, and they discovered CXCL1 promoted tumor growth through VEGF pathway activation . In addition, it had been reported that lymphatic endothelial cells could produce CXCL1 and Wang et al. showed CXCL1 secreted by tumor-associated lymphatic endothelial cells could promote the lymph node metastasis of GC via activation integrin β1/FAK/AKT signaling . Determining the underlying mechanism is a prerequisite for determining the prognostic significance of CXCL1 expression. Therefore, more basic researches should be conducted to explore the potential mechanism of CXCL1 in cancer prognosis.
In our study, there were some limitations which should be further discussed in the present study. First, there was no consistent the cutoff value for defining high and low CXCL1 expression, which might lead to the bias of the results. Second, we could not obtain partial HR directly from the original papers. Thus, we had to calculate the HRs from the survival curves, which might not be precise enough. Third, All eligible articles were retrospective research in the meta-analysis, which might lead to a degree of bias.
In conclusion, our study revealed that elevated expression level of CXCL1 was significantly associated with poor OS in GC patients. Moreover, the expression level of CXCL1 was associated with clinicopathological features including TNM stage, lymph node metastasis and depth of tumor invasion.