Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China.
The Second Clinical Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430000, China.
BMC Cancer. 2024 Aug 2;24(1):948. doi: 10.1186/s12885-024-12682-z.
Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms.
This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes.
The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis.
Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed.
肝样腺癌（Hepatoid adenocarcinoma of the lung，HAL）是一种罕见的肺腺癌（Lung adenocarcinoma，LAC）亚型，其特征为肝样特征，且 5 年生存率低至约 8%。由于对这种疾病的了解有限，导致缺乏标准化的治疗方案，其发病机制的分子基础也在很大程度上尚未得到探索。为了弥补这些空白，本研究通过 191 例原发性 HAL 患者的数据，描述了治疗模式、预后因素和潜在的发病机制。
本研究分为两个队列：队列 1，由 110 例从监测、流行病学和最终结果（Surveillance, Epidemiology, and End Results，SEER）数据库中提取的患者组成；队列 2，由通过 PubMed、Web of Science 和 Scopus 数据库进行全面文献综述确定的 70 例患者组成，此外还包括 11 例来自同济医院的患者。采用 Cox 比例风险回归模型来确定独立的预后因素。通过 Kaplan-Meier 生存曲线评估以手术和化疗为中心的治疗方式的影响。此外，本研究还评估了一线治疗方案的疗效，并对鉴定的突变基因进行了基因本体论（Gene Ontology，GO）功能和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析。
HAL 患者的人口统计学和临床特征通常包括老年吸烟者，更倾向于在疾病晚期诊断，导致高死亡率。确定的关键预后指标包括疾病分期、化疗和手术干预。本研究提出了一种治疗策略，主张对 IV 期 HAL 患者进行化疗，对非 IV 期疾病患者进行手术。紫杉醇和铂类化疗联合治疗作为一线治疗方案具有疗效，免疫治疗和靶向治疗的联合应用显示出潜在的益处。基因分析强调了 HAL 和 LAC 之间的相似性，特别是异常的激酶活性（丝氨酸、苏氨酸和酪氨酸）和 PI3K-Akt 和 MAPK 信号通路的激活，这些都是 HAL 发病机制的促成因素。
尽管发病率相对较低，但本研究强调了治疗策略的重要性，并得出了可能的预后因素。由于报告有限，需要更深入地了解驱动 HAL 肿瘤发生和进展的分子机制。
