Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1

Kotoe Oshima, Ken Kato, Yoshinori Ito, Hiroyuki Daiko, Isao Nozaki, Satoru Nakagawa, Yuichi Shibuya, Takashi Kojima, Yasushi Toh, Morihito Okada, Shuichi Hironaka, Yuji Akiyama, Yoshito Komatsu, Kazuhiro Maejima, Hidewaki Nakagawa, Ritsuko Onuki, Momoko Nagai, Mamoru Kato, Keisuke Kanato, Aya KuchibaKenichi Nakamura, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P =.00252 (Bonferroni-adjusted significance level is.0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P <.05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.

Original languageEnglish
Pages (from-to)1018-1027
Number of pages10
JournalCancer science
Volume113
Issue number3
DOIs
Publication statusPublished - 2022 Mar

Keywords

  • esophageal squamous cell carcinoma
  • prognostic factor
  • stage I
  • tumor mutation burden
  • whole-exome sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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