Comprehensive analyses of N6-methyladenosine-related long noncoding RNA profiles with prognosis, chemotherapy response, and immune landscape in small cell lung cancer,Cancer Science

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Comprehensive analyses of N6-methyladenosine-related long noncoding RNA profiles with prognosis, chemotherapy response, and immune landscape in small cell lung cancer
Cancer Science ( IF 4.5 ) Pub Date : 2022-09-01 , DOI: 10.1111/cas.15553
Yuejun Luo _{1,

2} , Zhihui Zhang _{1,

2} , Bo Zheng ₃ , Peng Wu _{1,

2} , Guochao Zhang _{1,

2} , Lide Wang _{1,

2} , Qingpeng Zeng _{1,

2} , Zhaoyang Yang ₃ , Liyan Xue ₃ , Hua Zeng ₃ , Fengwei Tan ₁ , Qi Xue ₁ , Shugeng Gao ₁ , Nan Sun _{1,

2} , Jie He _{1,

2}

Affiliation

Small cell lung cancer (SCLC) is the most devastating subtype of lung cancer with no clinically available prognostic biomarkers. N⁶-methyladenosine (m⁶A) and noncoding RNAs play critical roles in cancer development and treatment response. However, little is known about m⁶A-related long noncoding RNAs (lncRNAs) in SCLC. We used 206 limited-stage SCLC (LS-SCLC) samples from two cohorts to undertake the first and most comprehensive exploration of the m⁶A-related lncRNA profile in SCLC and constructed a relevant prognostic signature. In total, 289 m⁶A-related lncRNAs were screened out. We then built a seven-lncRNA-based signature in the training cohort with 48 RNA sequencing data using univariate and multivariate Cox regression models. The signature was well validated in an independent cohort containing 158 cases with quantitative PCR data. In both cohorts, the signature divided patients into high- and low-risk groups with significantly different survival rates (both p < 0.001). Our signature predicted chemotherapy survival benefit in patients with LS-SCLC. Receiver operating characteristic and C-index analyses indicated that the signature was better at predicting prognosis and chemotherapy benefit than other clinicopathologic features. Moreover, the signature was identified as an independent predictor of prognosis and chemotherapy response in different cohorts. Furthermore, functional analysis showed that multiple activated immune-related pathways were enriched in the low-risk group. Additionally, the signature was also closely related to various immune checkpoints and inflammatory responses. We generated the first clinically available m⁶A-related lncRNA signature to predict prognosis and chemotherapy benefit in patients with LS-SCLC. Our findings could help optimize the clinical management of patients with LS-SCLC and inform future therapeutic targets for SCLC.

中文翻译：

N6-甲基腺苷相关长链非编码 RNA 谱与小细胞肺癌预后、化疗反应和免疫景观的综合分析

小细胞肺癌 (SCLC) 是最具破坏性的肺癌亚型，没有临床可用的预后生物标志物。N ⁶ -甲基腺苷 (m ⁶ A) 和非编码 RNA 在癌症发展和治疗反应中起着关键作用。然而，人们对 SCLC 中与 m ⁶ A 相关的长链非编码 RNA (lncRNA) 知之甚少。我们使用来自两个队列的 206 个有限阶段 SCLC (LS-SCLC) 样本对 SCLC 中的 m ⁶ A 相关 lncRNA 谱进行了首次也是最全面的探索，并构建了相关的预后特征。总计 289 m ⁶筛选出A相关的lncRNA。然后，我们使用单变量和多变量 Cox 回归模型在具有 48 个 RNA 测序数据的训练队列中构建了一个基于 7 个 lncRNA 的特征。该特征在包含 158 个具有定量 PCR 数据的病例的独立队列中得到了很好的验证。在这两个队列中，特征将患者分为生存率显着不同的高风险组和低风险组（p < 0.001)。我们的特征预测了 LS-SCLC 患者的化疗生存获益。接受者操作特征和 C 指数分析表明，该特征比其他临床病理特征更能预测预后和化疗获益。此外，该特征被确定为不同队列中预后和化疗反应的独立预测因子。此外，功能分析表明，多种激活的免疫相关通路在低风险组中得到丰富。此外，该特征还与各种免疫检查点和炎症反应密切相关。我们生成了第一个临床可用的 m ⁶A 相关 lncRNA 特征预测 LS-SCLC 患者的预后和化疗获益。我们的研究结果可能有助于优化 LS-SCLC 患者的临床管理，并为 SCLC 的未来治疗目标提供信息。

更新日期：2022-09-01

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