Lavery Anita, Turkington Richard C
Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.
Gastroenterol Rep (Oxf). 2021 Jan 8;8(6):411-424. doi: 10.1093/gastro/goaa065. eCollection 2020 Dec.
Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%-30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.
食管癌是一种预后较差的毁灭性疾病，是全球第六大癌症死亡原因。在可切除疾病的情况下，有明确证据表明新辅助化疗和放化疗可提高生存率。令人失望的是，只有15%-30%的患者对新辅助治疗有组织病理学反应，且往往伴随着显著的毒性。在这种情况下，常规临床应用中没有预测性生物标志物，对患者进行治疗分层的能力可显著改善预后。在本综述中，我们旨在概述评估食管癌新辅助治疗预测性转录组生物标志物的当前进展，并讨论这种情况下生物标志物开发面临的挑战。我们将这些问题置于生物标志物开发和报告建议的更广泛背景中。大多数研究集中在信使核糖核酸（mRNA）和微小核糖核酸（miRNA）生物标志物上。这些研究报告了一系列参与多种途径和生物过程的不同基因，这在很大程度上是由所使用的不同平台和分析方法所解释的。许多研究的样本量也严重不足，因此不适合识别候选生物标志物。虽然对食管癌的多种分子亚型与临床结果之间的关系知之甚少，但已经提出了多种分子亚型。我们预计，未来几年积累的丰富基因组和转录组数据以及临床试验合作将为这种预后不良的疾病患者分层提供独特机会，并建议未来的生物标志物开发纳入精心设计的回顾性和前瞻性分析。
