Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
Cells. 2022 Jun 16;11(12):1944. doi: 10.3390/cells11121944.
Long-Interspersed Nuclear Element (L1) retrotransposons are silenced in healthy tissues but unrepressed in cancer. Even if L1 reactivation has been associated with reduced overall survival in breast cancer (BC) patients, a comprehensive correlation with clinicopathological features is still missing.
Using quantitative, reverse-transcription PCR, we assessed L1 mRNA expression in 12 BC cells, 210 BC patients and in 47 normal mammary tissues. L1 expression was then correlated with molecular and clinicopathological data.
We identified a tumor-exclusive expression of L1s, absent in normal mammary cells and tissues. A positive correlation between L1 expression and tumor dedifferentiation, lymph-node involvement and increased immune infiltration was detected. Molecular subtyping highlighted an enrichment of L1s in basal-like cells and cancers. By exploring disease-free survival, we identified L1 overexpression as an independent biomarker for patients with a high risk of recurrence in hormone-receptor-negative BCs.
Overall, L1 reactivation identified BCs with aggressive features and patients with a worse clinical fate.
长散布核元件（L1）反转录转座子在健康组织中被沉默，但在癌症中未被抑制。尽管 L1 的重新激活与乳腺癌（BC）患者的总生存率降低有关，但与临床病理特征的全面相关性仍然缺失。
我们使用定量逆转录 PCR 评估了 12 个 BC 细胞系、210 个 BC 患者和 47 个正常乳腺组织中的 L1 mRNA 表达。然后，将 L1 表达与分子和临床病理数据相关联。
我们发现 L1 在正常乳腺细胞和组织中不存在肿瘤特异性表达。检测到 L1 表达与肿瘤去分化、淋巴结受累和免疫浸润增加之间存在正相关。分子亚型分析突出显示 L1 在基底样细胞和癌症中富集。通过探索无病生存，我们发现 L1 过表达是激素受体阴性 BC 中复发风险较高的患者的独立生物标志物。
总的来说，L1 的重新激活鉴定出了具有侵袭性特征的 BC 患者和临床预后较差的患者。
