Transcriptional Expressions of CXCL9/10/12/13 as Prognosis Factors in Breast Cancer

Abstract

CXCLs play critical roles in antitumor immunity by activating tumor-specific immune responses and stimulating tumor proliferation, thus affecting patient outcomes. However, the expression and prognostic values of CXCLs in breast cancer have not been well clarified. The aim of this study was to investigate the impact of CXCLs transcriptional expression on breast cancer patients. Oncomine database, GEPIA (Gene Expression Profiling Interactive Analysis), UALCAN, Kaplan–Meier Plotter, TIMER (Tumor Immune Estimation Resource), and DAVID were used in our study. The transcriptional levels of CXCL9/10/11/13 in breast cancer tissues were significantly elevated while the transcriptional levels of CXCL1/2/3/12 were decreased based on intersections of Oncomine database and GEPIA. Among them, breast cancer patients with high transcriptional levels of CXCL2/9/10/12/13 and low transcriptional level of CXCL3 were associated with a better prognosis. We also found that most of CXCLs expressions are significantly correlated with known prognostic factors, such as patient’s age, major subclasses, individual cancer stages, and nodal metastasis status. In addition, the expression of CXCL9/10/12/13 was also indicated to be correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). The functions of differentially expressed CXCLs are primarily related to the immune response and cytokine-cytokine receptor interactions. Our results may provide novel evidence of new prognostic or predictive biomarkers for breast cancer patients.

Blockade of αvβ8 integrin synergizes with checkpoint inhibition to enhance anti-tumor immunity through Cxcl9-dependent augmentation of CD8+ T cell cytotoxicity

“…Our findings are in line with previous studies which have shown that increased Ifn expression, Ifn signaling, and activity of the Cxcl9/10-Cxcr3 chemokine axis are associated with improved prognosis for a variety of solid tumors. [23][24][25][26][27] Ifn expression in the TME has been described to enhance tumor cell killing through differentiation and activation of CD8+ T cells, rescue of exhausted CD8+ T cells, and upregulation of MHC class II in various immune cell populations. 27,28 Meta-analysis studies of patient data consistently correlate Ifn gene signatures with better prognoses, 24,29 and loss of Ifn appears to correlate with resistance to checkpoint inhibition therapy.…”

The Prognostic Value of the m6A Score in Multiple Myeloma Based on Machine Learning

“…HMGB1 is one of the damage-associated molecular patterns (DAMP) and plays a multifunctional role in inflammation and the development of cancer (such as colorectal cancer) [32,33]. It has been reported that CXCL9 is associated with the infiltration of immune cells and affects the prognosis of breast cancer patients [34]. HAVCR2 inhibitors have been proven to have certain tumor-suppressive effects in various preclinical tumor models [35].…”

Chemokines in the Landscape of Cancer Immunotherapy: How They and Their Receptors Can Be Used to Turn Cold Tumors into Hot Ones?

“…ER-Negative Breast Cancer patients also showed a good prognosis associated with immune cells infiltration in suggesting CXCL9 as a potential biomarker for the prognosis of this disease [ 224 ]. Another recent study also reported that in breast cancer high expression of CXCL9 and CXCL10 is associated with a good prognosis [ 225 ].…”

“…CXCL10 is largely produced by monocytic cells, endothelial cells, and fibroblasts whereas CXCL9 is also largely produced by CD103 + dendritic cells within the TME [ 198 ]. Importantly, CXCL10 and CXCL9 are highly expressed by human cancer cells, and this expression is correlated with a good prognosis [ 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 ].…”