Decreased expression of autophagy protein LC3 and sternness (CD44+/CD24-/low) indicate poor prognosis in triple-negative breast cancer
Decreased expression of autophagy protein LC3 and sternness (CD44+/CD24-/low) indicate poor prognosis in triple-negative breast cancer
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DOI：
10.1016/j.humpath.2015.09.034
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发表时间：
2016-02-01
期刊：
影响因子：
3.3
通讯作者：
Kwan, Aij-Lie
中科院分区：
文献类型：
--
作者：
Chang, Shu-Jyuan;Ou-Yang, Fu;Kwan, Aij-Lie
本研究评估了自噬蛋白轻链3（LC 3）表达的预后价值以及LC 3和干细胞标志物CD 44 +/CD 24-/low共表达在三阴性乳腺癌（TNBC）中的预后价值。采用免疫组化法检测67例TNBC患者肿瘤组织中LC 3和LC 3/CD 44 +/CD 24-/low免疫表型。LC 3阳性表达30例（44.78%）。在单变量（P=.0006）和多变量（P=.0153）分析中，LC 3表型与总生存期呈显着负相关。在67例TNBC患者中，24例（35.82%）观察到LC 3-/CD 44 +/CD 24-/low表型。根据Kaplan-Meier分析，具有LC 3-/CD 44 +/CD 24-/低表型的肿瘤的预后显著更差（P = 0.0280）。多因素分析显示LC 3-/CD 44 +/CD 24-/low表型是影响总生存率的独立预后指标。这些结果表明LC 3抑制成熟肿瘤细胞和癌症干细胞（CSC）中的TNBC。总之，这项研究表明，CSC与TNBC中自噬的进展有关。在INBC的进展和发展过程中，CSC/祖细胞的自噬较低。LC 3-/CD 44 +/CD 24-/低免疫表型表明与不良预后相关的高度侵袭性TNBC亚组。本研究调查了LC 3缺陷可能抑制成熟肿瘤细胞和CSC中的TNBC。因此，合理的推断是诱导自噬可能是TNBC的有效治疗策略。(C)2015 Elsevier Inc. All rights reserved.
This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and sternness markers CD44+/CD24-/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24-/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3 was expressed in 30 (44.78%) cases. The LC3 phenotype revealed a significant negative association with overall survival in both univariate (P=.0006) and multivariate (P=.0153) analyses. LC3-/CD44+/CD24-/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3-/CD44+/CD24-/low phenotype (P =.0280). Multivariate analysis indicated that LC3-/CD44+/CD24-/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of INBC, autophagy of CSCs/progenitor cells is low. LC3-/CD44+/CD24-/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC. (C) 2015 Elsevier Inc. All rights reserved.