Correlation between CXCR4, CXCR5 and CCR7 expression and survival outcomes in patients with clinical T1N0M0 non‐small cell lung cancer

Abstract

Background: Lung cancer is the leading cause of cancer-related death. Even if early detection and treatment have proven to be effective, the survival outcomes are still poor. Methods: Tissue samples and clinicopathological data of 244 patients with clinical T1N0M0 NSCLC were collected. We investigated CXCR4, CXCR5 and CCR7 expression levels using the immunohistochemical method and analyzed their correlations with clinicopathological characteristics and survival outcomes. Results: Elevated expression levels of CXCR4, CXCR5 and CCR7 were found in tumor tissues (P < 0.001). The expression levels were remarkably different in histological type (CXCR4, P = 0.032; CXCR5, P < 0.001; CCR7, P < 0.001) and LVI (CXCR4, P = 0.017; CXCR5, P = 0.030; CCR7, P < 0.001). In addition, CXCR4 and CXCR5 expression were significantly different in tumor differentiation (CXCR4, P < 0.001; CXCR5, P < 0.001). Survival analysis showed that patients with positive CXCR4 expression had a significantly lower five-year DFS (P = 0.007) and a lower five-year OS (P = 0.010). Patients in the CXCR5 positive group had a significantly lower five-year DFS (P = 0.038) and a lower five-year OS (P = 0.220), which were statistically insignificant. However, five-year DFS and five-year OS of patients with positive CCR7 expression were significantly higher (DFS: P < 0.001; OS: P < 0.001). CXCR5 and CCR7 expression were found to be independent prognostic factors through multivariate analysis. Conclusions: Expression levels of CXCR4, CXCR5 and CCR7 were significantly higher in tumor tissues, and expression of CXCR5 and CCR7 were independent prognostic factors for survival. Moreover, all three chemokines were correlated to the survival outcomes of patients with clinical T1N0M0 NSCLC, providing potential prognosticators and therapy targets for lung cancer treatment.

C-C Chemokine Receptor 7 in Cancer

“…Enhanced expression levels of CXCR4, CXCR5 and CCR7 were found in tumor tissues compared to normal tissue. Moreover, 5 year disease-free survival and 5 year overall survival were significantly higher for lung cancer patients with positive expression for all three chemokine receptors compared to controls with CCR7 expression having the highest significance ( p < 0.001 for both survival parameters) [ 220 ]. It is not obvious why these two studies buck the trend and suggest that CCR7 is the good guy; however, a recent bioinformatics study looked at various chemokine receptor expression patterns, including CCR7 expression, in relation to NSCLC stage compared to normal tissue and reported that CCR7 was expressed at all stages with higher expression in early stages that tails off as the tumor progresses [ 221 ].…”

Comprehensive analysis of the immunological implication and prognostic value of CXCR4 in non-small cell lung cancer

“…Previous studies have shown that CXCR4 is highly expressed in NSCLC and is related to the prognosis of patients [ 21 ]; however, the same in both the LUAD and LUSC subgroups has not been shown before. We confirmed the prognostic value of CXCR4 in LUAD and LUSC patients based on an independent cohort—high CXCR4 expression predicts poor patient prognosis.…”

“…However, the potential of CXCR4 as a tumor immune prognostic marker has not been extensively studied, especially in NSCLC. To the best of our knowledge, the prognostic value of CXCR4 in NSCLC has been assessed in small-scale samples [ 21 ] but the relationship between CXCR4 and immune markers has not been established.…”

CXCR5+CD8 T cells: Potential immunotherapy targets or drivers of immune-mediated adverse events?

“…CXCR5 + CD8 T cells correlate with disease-free or overall survival in pancreatic, colon, follicular lymphoma, gastric, high-grade serous ovarian, hepatocellular, and bladder cancers and thus is considered a potential biomarker ( 15 , 17 , 20 , 23 , 25 , 26 ). On the contrary, decreases in disease-free survival in non-small cell lung and salivary adenoid cystic carcinomas are associated with infiltrating CXCR5 + CD8 T cells ( 74 , 75 ). Functional studies beyond correlative data and mRNA expression remains lacking as to how these cells benefit or negate a tumor microenvironment.…”