Department of Gynecological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Cancer Med. 2024 Jun;13(11):e7389. doi: 10.1002/cam4.7389.
Ion channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non-coding RNA genes are widely involved in ion channel-related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored.
Thirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer-specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion-channel-related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated.
To comprehensively identify cervical cancer-specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel- and tumorigenesis-related (ICTR-) lncRNAs were identified. Based on nine ICTR-lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR-lncRNAs signature scores.
We provided a thorough landscape of cervical cancer-specific lncRNAs. Through integrative analyses, we identified ion-channel-related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.
离子通道在宫颈癌的发生和进展中起着重要作用。许多长非编码 RNA 基因广泛参与离子通道相关信号调节。然而，lncRNAs 与宫颈癌预后的关联及其潜在的临床应用仍未得到充分探索。
本研究纳入了 13 名宫颈癌患者。对患者手术切除的新鲜肿瘤组织和相邻正常组织进行全转录组（涉及 mRNA 和 lncRNA）测序。通过我们的定制管道获得了全面的宫颈癌特异性 lncRNA 图谱。然后，通过回归算法建立了一个与离子通道相关的 lncRNA 预后评分模型。进一步评估了预测模型的性能及其与临床特征和肿瘤微环境（TME）状态的关联。
为了全面鉴定宫颈癌特异性 lncRNAs，我们对 26 例宫颈癌患者的样本进行了测序，并整合了转录组结果。我们构建了一个定制的分析管道，以提高 lncRNA 鉴定和功能注释的准确性，并在宫颈癌中获得了 18482 个新的 lncRNAs。然后，鉴定出 159 个与离子通道和肿瘤发生相关（ICTR）的 lncRNAs。基于这 9 个 ICTR-lncRNAs，我们还建立了一个预后评分模型，并验证了其在评估宫颈癌患者预后中的准确性和稳健性。此外，对 TME 进行了特征分析，我们发现 B 细胞、激活的 CD8+T 细胞和三级淋巴结构与 ICTR-lncRNAs 特征评分显著相关。
我们提供了宫颈癌特异性 lncRNAs 的全面图谱。通过综合分析，我们鉴定了与离子通道相关的 lncRNAs，并建立了一个预测模型来评估宫颈癌患者的预后。同时，我们还对其与 TME 状态的关联进行了特征分析。本研究提高了我们对 lncRNAs 在宫颈癌中调节离子通道的重要作用的认识。
