Department of Otolaryngology-Head and Neck Surgery, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
BMC Cancer. 2018 Mar 2;18(1):248. doi: 10.1186/s12885-018-4161-8.
As hybrid RNAs, transcription-induced chimeras (TICs) may have tumor-promoting properties, and some specific chimeras have become important diagnostic markers and therapeutic targets for cancer.
We examined 23 paired laryngeal cancer (LC) tissues and adjacent normal mucous membrane tissue samples (ANMMTs). Three of these pairs were used for comparative transcriptomic analysis using high-throughput sequencing. Furthermore, we used real-time polymerase chain reaction (RT-PCR) for further validation in 20 samples. The Kaplan-Meier method and Cox regression model were used for the survival analysis.
We identified 87 tumor-related TICs and found that COL7A1-UCN2 had the highest frequency in LC tissues (13/23; 56.5%), whereas none of the ANMMTs were positive (0/23; p < 0.0001). COL7A1-UCN2, generated via alternative splicing in LC tissue cancer cells, had disrupted coding regions, but it down-regulated the mRNA expression of COL7A1 and UCN2. Both COL7A1 and UCN2 were down-expressed in LC tissues as compared to their paired ANMMTs. The COL7A1:β-actin ratio in COL7A1-UCN2-positive LC samples was significantly lower than that in COL7A1-UCN2-negative samples (p = 0.019). Likewise, the UCN2:β-actin ratio was also decreased (p = 0.21). Furthermore, COL7A1-UCN2 positivity was significantly associated with the overall survival of LC patients (p = 0.032; HR, 13.2 [95%CI, 1.2-149.5]).
LC cells were enriched in the recurrent chimera COL7A1-UCN2, which potentially affected cancer stem cell transition, promoted epithelial-mesenchymal transition in LC, and resulted in poorer prognoses.
转录诱导嵌合体（TICs）作为杂交 RNA，可能具有促进肿瘤的特性，某些特定的嵌合体已成为癌症的重要诊断标志物和治疗靶点。
我们检查了 23 对喉癌（LC）组织和相邻正常黏膜组织样本（ANMMTs）。其中 3 对用于使用高通量测序进行比较转录组分析。此外，我们在 20 个样本中使用实时聚合酶链反应（RT-PCR）进行进一步验证。使用 Kaplan-Meier 方法和 Cox 回归模型进行生存分析。
我们鉴定了 87 个与肿瘤相关的 TICs，发现 COL7A1-UCN2 在 LC 组织中频率最高（13/23；56.5%），而在任何 ANMMTs 中均未检测到（0/23；p<0.0001）。COL7A1-UCN2 通过 LC 组织癌细胞中的选择性剪接产生，具有破坏的编码区，但它下调了 COL7A1 和 UCN2 的 mRNA 表达。与配对的 ANMMTs 相比，COL7A1 和 UCN2 在 LC 组织中均下调表达。COL7A1-UCN2 阳性 LC 样本中的 COL7A1:β-肌动蛋白比值明显低于 COL7A1-UCN2 阴性样本（p=0.019）。同样，UCN2:β-肌动蛋白比值也降低（p=0.21）。此外，COL7A1-UCN2 阳性与 LC 患者的总生存率显著相关（p=0.032；HR，13.2[95%CI，1.2-149.5]）。
LC 细胞富含潜在影响癌症干细胞转化的复发性嵌合体 COL7A1-UCN2，促进 LC 中的上皮-间充质转化，并导致预后较差。
