Jansson Malin, Lindberg Jessica, Rask Gunilla, Svensson Johan, Billing Ola, Nazemroaya Anoosheh, Berglund Anette, Wärnberg Fredrik, Sund Malin
Department of Surgery and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden.
Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
Front Mol Biosci. 2022 May 25;9:904526. doi: 10.3389/fmolb.2022.904526. eCollection 2022.
Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with and small invasive breast cancers (≤15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated ( = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis ( = 0.002). In an external validation cohort ( = 1,104), high type IV collagen mRNA expression was significantly ( = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.
乳腺癌是全球女性癌症死亡的最常见原因。局限性乳腺癌可通过手术和辅助治疗治愈，但对于早期发生转移的肿瘤，死亡率仍然很高。IV型胶原蛋白是一种基底膜蛋白，这种细胞外基质结构的破坏是癌症侵袭的第一步。IV型胶原蛋白存在于许多癌症的基质中，但其在肿瘤生物学中的作用尚不清楚。在此，分析了IV型胶原蛋白在小乳腺癌基质中的表达，并将其与临床使用的预后生物标志物和患者生存率相关联。这些发现进一步在一个独立的基因表达数据队列中得到验证。纳入了1986年至2004年诊断为小浸润性乳腺癌（≤15毫米）的1379名女性的组织样本。将原发性肿瘤组织收集到组织微阵列中。使用免疫组织化学观察组织中IV型胶原蛋白的表达。从癌症基因组图谱数据库中提取基因表达数据。在1379名女性中，856人患有浸润性乳腺癌，714名患者有IV型胶原蛋白染色结果。在Kaplan-Meier分析中，IV型胶原蛋白高表达与较差的乳腺癌特异性生存率显著相关（P = 0.026）。IV型胶原蛋白表达与临床使用的预后生物标志物无相关性。IV型胶原蛋白高表达与远处转移明显相关（P = 0.002）。在一个外部验证队列（n = 1104）中，IV型胶原蛋白mRNA高表达与较差的总生存率显著相关（P = 0.041），转移组织中IV型胶原蛋白mRNA过表达。原发性肿瘤中的基质IV型胶原蛋白表达与较差的乳腺癌特异性生存率相关，最可能的原因是发生远处转移的风险较高。这种细胞外基质蛋白可能作为一种生物标志物来预测乳腺癌患者未来发生转移疾病的风险。
