Klahan Sukhontip, Wong Henry Sung-Ching, Tu Shih-Hsin, Chou Wan-Hsuan, Zhang Yan-Feng, Ho Thien-Fiew, Liu Chih-Yi, Yih Shih-Ying, Lu Hsing Fang, Chen Sean Chun-Chang, Huang Chi-Cheng, Chang Wei-Chiao
1 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University.
2 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Tumour Biol. 2017 Jun;39(6):1010428317705573. doi: 10.1177/1010428317705573.
Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.
手术是乳腺癌患者最有效的治疗方法。然而,一些患者术后出现复发和远处转移。根据多种预后标志物,高危患者会考虑进行辅助治疗,而淋巴管浸润已成为帮助医生识别远处转移和复发风险的此类预后标志物之一。然而,乳腺癌中淋巴管浸润的机制仍不清楚。本研究旨在揭示可能参与乳腺癌淋巴管浸润的基因和通路。总共在手术期间收集了108份乳腺癌样本,并进行了微阵列分析。使用微阵列的显著性分析和R语言的limma软件包来检测淋巴管浸润阳性和阴性病例之间的差异表达基因。使用Ingenuity Pathway Analysis和注释、可视化与整合发现数据库进行网络和通路分析。在淋巴管浸润阳性患者中总共鉴定出86个差异表达基因,包括37个下调基因和49个上调基因。在这些基因中,TNFSF11、IL6ST和EPAS1在细胞因子-受体相互作用中起重要作用,这是与淋巴管浸润最相关的富集通路。此外,结果还表明细胞外基质成分与肿瘤微环境之间的失衡可能诱导淋巴管浸润。我们的研究评估了淋巴管浸润的潜在机制,这可能进一步有助于评估乳腺癌进展的风险并确定辅助治疗的潜在靶点。