Phosphorylated CXCR4 expression has a positive prognostic impact in colorectal cancer

被引：11

作者：

Weixler, B. ^{[1
]}

Renetseder, F. ^{[1
]}

Facile, I. ^{[1
]}

Tosti, N. ^{[2
]}

Cremonesi, E. ^{[3
]}

Tampakis, A. ^{[1
]}

Delko, T. ^{[1
]}

Eppenberger-Castori, S. ^{[2
]}

Tzankov, A. ^{[2
]}

Iezzi, G. ^{[3
]}

Kettelhack, C. ^{[1
]}

Soysal, S. D. ^{[1
]}

von Holzen, U. ^{[4
,5
]}

Spagnoli, G. C. ^{[3
]}

Terracciano, L. ^{[2
]}

Tornillo, L. ^{[2
]}

Droeser, Raoul A. ^{[1
]}

Daster, S. ^{[1
]}

机构：

[1] Univ Hosp Basel, Dept Surg, Basel, Switzerland

[2] Univ Basel, Inst Pathol, Basel, Switzerland

[3] Univ Basel, Dept Biomed, Basel, Switzerland

[4] Indiana Univ Sch Med South Bend, Goshen Ctr Canc Care, Goshen, IN USA

[5] Harper Canc Res Inst, South Bend, IN USA

来源：

CELLULAR ONCOLOGY | 2017年 / 40卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

CXCR4; pCXCR4; Colorectal cancer; Prognostic significance; CRC; CHEMOKINE RECEPTOR CXCR4; CELL LUNG-CANCER; CARCINOMA; RISK; ASSOCIATION; BIOMARKERS; SURVIVAL; TUMORS; AXIS;

D O I：

10.1007/s13402-017-0348-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The CXCL12-CXCR4 chemokine axis plays an important role in cell trafficking as well as in tumor progression. In colorectal cancer (CRC), the chemokine receptor CXCR4 has been shown to be an unfavorable prognostic factor in some studies, however, the role of its activated (phosphorylated) form, pCXCR4, has not yet been evaluated. Here, we aimed to investigate the prognostic value of CXCR4 and pCXCR4 in a large cohort of CRC patients. A tissue microarray (TMA) of 684 patient specimens of primary CRCs was analyzed by immunohistochemistry (IHC) for the expression of CXCR4 and pCXCR4 by tumor cells and tumor-infiltrating immune cells (TICs). The combined high expression of CXCR4 and pCXCR4 showed a favorable 5-year overall survival rate (68%; 95%CI = 59-76%) compared to tumors showing a high expression of CXCR4 only (48%; 95%CI = 41-54%). High expression of pCXCR4 was significantly associated with a favorable prognosis in a test and validation group (p = 0.015 and p = 0.0001). Moreover, we found that CRCs with a high density of pCXCR4+ tumor-infiltrating immune cells (TICs) also showed a favorable prognosis in a test and validation group (p = 0.054 and p = 0.004). Univariate Cox regression analysis for TICs revealed that a high density of pCXCR4+ TICs was a favorable prognostic marker for overall survival (HR = 0.97,95%CI = 0.96-1.00; p = 0.01). In multivariate Cox regression survival analyses a high expression of pCXCR4 in tumor cells lost its association with a better overall survival (HR = 0.99; 95%CI = 0.99-1.00, p = 0.098). Our results show that high densities of CXCR4 and pCXCR4 positive TICs are favorable prognostic factors in CRC.

引用

页码：609 / 619

页数：11

共 43 条

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