CXCL5 as a potential novel prognostic factor in early stage non-small cell lung cancer: results of a study of expression levels of 23 genes

Abstract

As the current staging system is imprecise for estimating prognosis of early stage non-small cell lung cancer (NSCLC), it is important to identify other methods for selecting high-risk patients after failed surgical treatment. The aim of the study was to evaluate the expression of 23 genes as putative prognostic markers in early stage NSCLC. The study was performed on 109 pairs of tumor and matched unaffected lung tissue surgical specimens taken from stage I and II NSCLC patients. We evaluated the mRNA level of 23 genes using the real-time PCR method. The difference in the expression between the tumor and normal tissue for each gene was analyzed using a general linear model. The influence of gene expression on survival was analyzed by using the proportional hazards model. Eighteen out of the 23 genes showed statistically significant differences in expression between the tumor and non-tumor tissue. For 12 genes (ITGB1, ITGB3, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, CXCR3, CXCR4, TNF, CHKA, AGFG1, and CTC1), the expression was lower, and for six genes (ITGA5, IL8, IL6, CXCL2, CXCL3, and CXCL12), it was higher in the tumor tissue as compared to the matched normal tissue. Expression changes were more pronounced in squamous cell carcinomas than in adenocarcinomas or large cell carcinomas. Of all the analyzed genes, only CXCL5 was found to statistically significantly (p = 0.04) influence both overall and disease-free survival. Among the 23 genes previously suggested to be relevant for early staged NSCLC patients’ postoperative outcome, only CXCL5 showed a statistically significant prognostic effect.

Myeloid-Derived Suppressor Cell Subset Accumulation in Renal Cell Carcinoma Parenchyma Is Associated with Intratumoral Expression of IL1β, IL8, CXCL5, and Mip-1α

“…The correlation of I-MDSC with IL-8 and CXCL5 is especially interesting, given that little is known about the factors that draw I-MDSC into the tumor parenchyma. Interestingly, CXCL5 expression has been associated with decreased survival in a number of human tumors (55), and IL-8 levels were recently shown to correlate with PFS and OS in mRCC (54) (for CXCL-5, these were studies on tumor parenchyma, whereas with IL-8 this was a study on circulating protein).…”

DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling

“…On the other hand, high expression of CXCL5 predicts worse prognosis for both RFS and OS. In deed, recent studies analyzed the effect of 18 out of the 23 differently expressed genes between the tumor and normal tissues on overall survival, only CXCL5 had significantly influence on overall and disease-free survival [36]. …”

CXCL9: evidence and contradictions for its role in tumor progression

“…Metodieva et al also showed a high expression level of CXCL9 in 12 NSCLC patients [37]. However, a study by Kowalczuk et al also showed that CXCL9 expression was low in 109 NSCLC tumor tissues, but it could not influence both overall and disease-free survival [38]. In addition, other studies have also demonstrated that Egr-1 deficiency [22], IL-7 [39], CCL21 [40], and myeloid-derived suppressor cells depletion [41] reduced tumor burden by upregulating CXCL9 and CXCL10 expression, which played an anti-angiogenic role and attracted tumor macrophages, CD4 and CD8+ T lymphocytes, and NK cells.…”