PO.CL12.01 · 临床研究

早期肺类癌肿瘤的基因组-免疫表型图谱及其预后意义

Genomic-immunophenotypic landscape of early-stage pulmonary carcinoid tumors and their prognostic implications

编号 3889 展板 22 时间 4/20 02:00–05:00 区域 Section 46 主讲 SIbo Peng

分会场 Molecular Classification and Tumor Biology in Cancer

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作者与单位 Authors & Affiliations

Song Xu¹, Lingling Zu¹, Ning Zhou¹, Jingya Wang², Xiongfei Li³, Haixiang Yu⁴, Sibo Peng¹, Chunxia Su⁵, Dingzhi Huang²

¹Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China, Tianjin, China,²Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention on and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China., Tianjin, China,³Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China., Shanghai, China,⁴Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China, Changchun, China,⁵Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China, Shanghai, China

摘要 Abstract

中文摘要

背景：肺类癌(pulmonary carcinoids, PCs)包括不典型类癌(atypical carcinoids, ACs)和典型类癌(typical carcinoids, TCs)，是一类罕见的肺癌，以低至中度恶性为特征。然而，从全球范围来看，人们对PCs相关的基因组和免疫特征了解有限。方法：本研究纳入126例可手术切除的PC患者，包括44例ACs和82例TCs。采用578基因panel进行二代测序，并进行PD-L1和CD8的免疫组化染色。发现：PCs中最常发生改变的基因为EGFR(n=16，18%)、KMT2C(n=11，12%)、LRP1B(n=10，11%)、MEN1(n=10，11%)和NOTCH2(n=9，10%)。这些PCs中普遍观察到RTK/RAS、NOTCH和PI3K通路的失调。我们的研究揭示，仅有4.6%的PC患者被鉴定为PD-L1阳性，且早期PCs中TMB和CD8+ T细胞浸润较低，表现为"免疫排斥"或"免疫荒漠"型微环境。我们确定年龄、性别、TNM分期、肿瘤类型、吸烟状态、TMB和LRP1B突变为预后不良的指标。我们发现，对于那些携带LRP1B突变的可手术切除早期PC患者，其肿瘤相关死亡和复发风险增加，并据此进一步提出了基于LRP1B突变状态的分子分型。解读：我们描绘了PCs的遗传和免疫图谱，并提出了基于LRP1B突变的分子分型。我们的研究为PCs的生物学机制提供了新的见解，有助于PC患者的个体化治疗。

查看英文原文 English abstract

Background: Pulmonary carcinoids (PCs), encompassing atypical carcinoids (ACs) and typical carcinoids (TCs), represent a rare category of lung cancer characterized by low to moderate malignancy. However, there is a limited understanding of the genomic and immune characteristics associated with PCs on a global scale. Methods: This study enrolled 126 surgically resectable PC patients, comprising 44 ACs and 82 TCs. Next-generation sequencing utilizing a 578-gene panel was conducted and immunohistochemical staining for PD-L1 and CD8 was also carried out. Findings: The most frequently altered genes in PCs were identified as EGFR (n=16, 18%), KMT2C (n=11, 12%), LRP1B (n=10, 11%), MEN1 (n=10, 11%), and NOTCH2 (n=9, 10%). Dysregulation of the RTK/RAS, NOTCH, and PI3K pathways was commonly observed in these PCs. Our study unveiled that only 4.6% of the PC patients were identified as PD-L1 positivity, and TMB and CD8+ T cell infiltration were found to be low in early-stage PCs, as manifested by the “immune-excluded” or “immune-desert” microenvironment. We identified age, gender, TNM stage, tumor type, smoking status, TMB, and LRP1B mutation as indicators of poor prognosis. We found that for those surgically resectable early-stage PC patients with LRP1B mutation, patients exhibit an increased risk for tumor-related mortality and recurrence, and subsequently further proposed a molecular classification based on the status of LRP1B mutation. Interpretation: We depicted the genetic and immune landscape of PCs and proposed a LRP1B mutation based molecular classification. Our research offers novel insights into the biological mechanisms of PCs which contributes to the individualized treatment for PC patients.

利益披露 Disclosure

S. Xu, None.. L. Zu, None.. N. Zhou, None.. J. Wang, None.. X. Li, None.. H. Yu, None.. S. Peng, None.. C. Su, None.. D. Huang, None.

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