451基因panel分析65例单纯手术切除食管腺癌患者的基因组改变与生存相关性

Abstract

New prognostic biomarkers for oesophageal adenocarcinoma (OAC) may help treatment planning as current staging does not accurately predict survival for many patients. We used a 451 cancer-associated gene panel to assess genomic alterations associated with survival for a cohort of 65 OAC patients who underwent surgical resection without perioperative treatment, reflecting institutional practice at the time. Median age at operation was 72 years, 88% were male, median 32 lymph nodes were removed per patient, and minimum follow-up exceeded 11 years. TNM stages (pTNM, 8th ed.) were 14% stage 1, 14% stage 2, 45% stage 3, and 6% stage 4 (non-locoregional nodal metastases). Copy number changes were common, and somatic mutations were similar to those reported previously. Genetic associations with worse survival included amplification of CCND1 (HR=3.08, p=0.02), EGFR (HR=2.98, p=0.01), loss of ARID2 (HR=2.12, p=0.05), KMT2D (HR=1.99, p=0.07) and missense mutation within RYR1 (HR=2.68, p=0.01). This study identifies candidate genomic prognostic biomarkers in OAC using a cohort treated by surgery alone, enabling assessment of tumour biology independent of the confounding effects of peri-operative systemic therapy and radiotherapy. Several of the identified alterations are potentially targetable, supporting further investigation of genomic profiling to refine prognostication and guide treatment selection.

Competing Interest Statement

The authors have declared no competing interest.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional ethics approval and material transfer agreement was obtained from Skane University Hospital, Lund, Sweden (2014/224) and from St. Vincents Hospital, Sydney, Australia (ETH03452). Informed consent was obtained from all participating individuals. All methods were carried out in accordance with relevant guidelines and regulations.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Data has been deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS50000002190 (https://ega-archive.org/studies/EGAS50000002190). Further information about EGA can be found at https://ega-archive.org and The European Genome-phenome Archive in 2021: 10.1093/nar/gkab1059. Analysis code and processed data are available at github.com/trinhan/EAC_Lund_En-bloc. Individual patient data are not available.

https://ega-archive.org/studies/EGAS50000002190

Funder Information Declared

NHMRC, 2012513

Bioplatforms Australia, https://ror.org/042gz1a70

Kinghorn foundation

St Vincents Clinic Foundation