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吲哚胺-2,3-双加氧酶和白细胞介素-6与乳腺癌新辅助化疗的肿瘤反应相关。

Indoleamine-2,3-dioxygenase and Interleukin-6 associated with tumor response to neoadjuvant chemotherapy in breast cancer.

作者信息

Li Fangxuan, Wei Lijuan, Li Shixia, Liu Juntian

机构信息

Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.

出版信息

Oncotarget. 2017 Nov 1;8(64):107844-107858. doi: 10.18632/oncotarget.22253. eCollection 2017 Dec 8.

Abstract

PURPOSE

Indoleamine-2,3-dioxygenase (IDO) and Interleukin-6 (IL-6) contribute to poor therapeutic effects, tumor relapse and aggressive tumor growth. IDO and IL-6 incorporate a positive feedback signal loop to maintain IDO and IL-6 constitutive expression and facilitate tumor progression.

RESULTS

IDO expression was associated with IL-6 expression and plasma IL-6 level (0.05). Concentrating on clinicopathological features prior neoadjuvant chemotherapy, both IDO expression and plasma IL-6 level were associated with clinical T stage and N stage (0.05). IL-6 expression was associated with clinical T stage (0.016). The co-expression of IDO/IL-6 was correlated with clinical T, N stage and estrogen receptor (ER) status (<0.05). IDO, IL-6 expression, clinical T stage, pathological T stage, ER status and Luminal type were correlated with clinical response to neoadjuvant chemotherapy (<0.05). Multivariate analysis showed that IDO expression were correlated with clinical response to neoadjuvant chemotherapy (0.034). IL-6 expression and pathological T stage were correlated with pCR (<0.05). In the multivariate analysis, postoperative pathological T stage associated with pCR (0.041). In the prognostic analysis, only clinical T stage was significant correlated with overall survival (=0.003).

MATERIALS AND METHODS

46 breast cancer patients received neoadjuvant chemotherapy enrolled in this study. Immunohistochemistry was applied for evaluating IDO and IL-6 expression in biopsy tissues prior neoadjuvant chemotherapy. Immunofluorescence was applied to observe the co-localization of IDO and IL-6. Serum IL-6 level was examined via ELISA. The associations between IDO, IL-6, Serum IL-6 level and clinicopathological features, response to neoadjuvant chemotherapy were analyzed.

CONCLUSION

IDO and IL-6 expression associated with advanced breast cancer and poor response to neoadjuvant chemotherapy.

摘要

目的

吲哚胺-2,3-双加氧酶(IDO)和白细胞介素-6(IL-6)会导致治疗效果不佳、肿瘤复发以及肿瘤的侵袭性生长。IDO和IL-6形成一个正反馈信号回路,以维持IDO和IL-6的组成型表达并促进肿瘤进展。

结果

IDO表达与IL-6表达及血浆IL-6水平相关(P<0.05)。聚焦于新辅助化疗前的临床病理特征,IDO表达和血浆IL-6水平均与临床T分期和N分期相关(P<0.05)。IL-6表达与临床T分期相关(P=0.016)。IDO/IL-6的共表达与临床T、N分期及雌激素受体(ER)状态相关(P<0.05)。IDO、IL-6表达、临床T分期、病理T分期、ER状态及管腔型与新辅助化疗的临床反应相关(P<0.05)。多因素分析显示,IDO表达与新辅助化疗的临床反应相关(P=0.034)。IL-6表达和病理T分期与病理完全缓解(pCR)相关(P<0.05)。在多因素分析中,术后病理T分期与pCR相关(P=0.041)。在预后分析中,仅临床T分期与总生存期显著相关(P=0.003)。

材料与方法

本研究纳入46例接受新辅助化疗的乳腺癌患者。应用免疫组织化学评估新辅助化疗前活检组织中IDO和IL-6的表达。应用免疫荧光观察IDO和IL-6的共定位。通过酶联免疫吸附测定法检测血清IL-6水平。分析IDO、IL-6、血清IL-6水平与临床病理特征、新辅助化疗反应之间的关联。

结论

IDO和IL-6表达与晚期乳腺癌及新辅助化疗反应不佳相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b4/5746108/9f8ba2ccc67f/oncotarget-08-107844-g001.jpg

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