GC is one of tumors of digestive tract with high morbidity and mortality, which is characterized by strong invasiveness, high recurrence and metastasis rate and poor survival [15,16,17]. Although the progression of surgical technology, radiotherapy, chemotherapy and other diagnostic and therapeutic technologies have significantly improved the prognosis of GC patients, the mortality rate is still high [18, 19]. At present, great progression has been made in understanding the pathogenesis of GC from the perspective of biology and genomics, which makes the targeted therapy of advanced GC enter clinical research and practice. Previously, researchers identified the SDF2 gene on human chromosome 17 qll.2 through in situ hybridization [20]. In addition, there is some evidence that SDF2 is involved in occurrence and development of malignant tumors. However, the expression and role of SDF2 in GC has not been reported. In our results, for the first time, we found: (1) SDF2 is high expression in GC tissues. (2) High expression of SDF2 is associated with Borrmann classification, depth of tumor invasion, positive lymph node metastasis and TNM stage of GC patients. (3) GC patients with high expression of SDF2 have significantly poor OS.
Previous studies have revealed that different expressions of SDF2 in several malignant tumors and is related to the prognosis of different tumors. For example, Vendrell et al. analyzed genomics and transcriptomics data in a series of Dukes B and C colorectal carcinomas, and 68 genes were identified, including low expression of SDF2 [11]. Takahashi et al. revealed that the SDF2 expression was up-regulated in oxaliplatin-resistant GC cells [21]. In our study, we found the different levels of SDF2 expression in GC tissue and normal gastric tissue through bioinformatics analysis. Furthermore, our results confirmed that the expression of SDF2 in GC tissue was higher than that in normal gastric tissue by western blot and immunohistochemistry.
SDF2 is one of the resident proteins of endoplasmic reticulum. It is reported that chronic ER stress is involved in cancer, diabetes and degenerative disease [22]. Moreover, Schott et al. demonstrated that SDF2 protein can be up-regulated by ER stress [13]. Further understand the mechanism of SDF2 in ER stress may help to identify its possible downstream targets in cancer [23]. Although the level of SDF2 expression has been detected in several types of tumors, there is no data to detect its clinicopathological significance of GC patients. Based on the data of 94 patients with GC, we found that the SDF2 expression was related with Borrmann classification, tumor invasion, positive lymph node metastasis and TNM stage. However, the expression of SDF2 was not related with gender, age, tumor size, histological differentiation. Furthermore, In the TCGA samples, the relationship between SDF2 expression and age, gender, tumor grade, lymph node metastasis, cancer stage of GC patients was analyzed, and the age was analyzed by age stratification. The results were consistent with the conclusions of our clinical data. These results indicated that SDF2 may be involved in the tumor malignant biological behavior, especially metastasis. These differences may be partly due to limitations of sample size. Therefore, this needs to be further studied in involving more patients with GC.
In recent years, many scholars began to explore the expression and role of SDF2 in tumors. Kang et al. demonstrated that different levels of SDF2 expression in breast cancer patients, and its upregulation was associated with better clinical outcomes [24]. In colorectal cancer, it has been reported that SDF2 expression is down-regulated, and the low expression of SDF2 may be associated with low survival rate [11]. Recent study has shown that the inhibition of SDF2 leads to the enhancement of Oxaliplatin-induced anti-proliferation and apoptosis, and SDF2 may be a new therapeutic target of Oxaliplatin-resistant GC cells [21]. At present, there is no study to detect the relationship between SDF2 expression and prognosis of GC patients. Consistent with the prognosis predicted by GEPIA database, our study showed that the OS of GC patients with SDF2 high expression was significantly poorer than that of GC patients with SDF2 low expression, and SDF2 expression may be an independent predictor of poor OS of GC patients.
In our research, several shortcomings cannot be ignored. First, it was a single center retrospective study, and the sample of included GC patients was relatively small. A multicenter study including large sample of GC patients is needed to detect the significance of SDF2 expression in GC patients. Second, we used immunohistochemistry to explore the SDF2 expression in GC tissue, and IRS method is a semi-quantitative score in each region which could not be representative of the whole region of GC tissue. Therefore, the heterogeneity in our study could not be ignored.
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