Scholarlink

Background <p><i>TP53</i> mutations are among the most frequent alterations in biliary tract cancer (BTC), but their prognostic relevance and predictive value for immune checkpoint inhibitors (ICI) remain unclear. We assessed clinico-molecular features, prognosis, and ICI efficacy by <i>TP53</i> status in advanced BTC.</p> Methods <p>Patients with advanced BTC from Japan and the United States who underwent tissue- or plasma-based next-generation sequencing were retrospectively analyzed. Tissue-based sequencing was used for the primary analysis, and plasma ctDNA sequencing was evaluated as an exploratory cohort. Outcomes were compared between <i>TP53</i> wild-type (WT) and <i>TP53</i>-mutated groups. Treatment–<i>TP53</i> interactions for non-ICI versus ICI-containing regimens were assessed using multivariable Cox models. Whole-transcriptome sequencing data were analyzed using TIDE and Hallmark gene set enrichment analysis.</p> Results <p>Among 336 patients in the tissue-based cohort, 177 (52.7%) had <i>TP53</i>-mutated tumors. <i>SMAD4, ERBB2, PTEN</i> and <i>CCNE1</i> co-alterations were enriched in <i>TP53</i>-mutated tumors, whereas <i>IDH1, BAP1</i>, and <i>FGFR2</i> fusions were more frequent in WT tumors. <i>TP53</i> mutations were independently associated with shorter PFS, whereas OS showed a similar but nonsignificant trend (PFS: HR 1.32, <i>P</i> = 0.04; OS: HR 1.32, <i>P</i> = 0.09). <i>TP53</i> mutations were associated with shorter PFS in the non-ICI cohort but numerically longer PFS in the ICI cohort, with a significant treatment–<i>TP53</i> interaction for PFS (<i>P</i> &lt; 0.01). Similar trends were observed in the plasma cohort. Transcriptomic analyses (<i>n</i> = 59; all MSS) showed lower TIDE scores in <i>TP53</i>-mutated tumors.</p> Conclusion <p><i>TP53</i> mutations were associated with poor prognosis and may predict greater benefit from ICI, supporting biomarker-driven stratification.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月25日

查看全文
  • Taro Shibuki,
  • Celine Hoyek,
  • Ryne Ramaker,
  • Madhuri Gottam,
  • Makoto Ueno,
  • Yasuyuki Kawamoto,
  • Shinji Itoh,
  • Kanae Inoue,
  • Tadayoshi Hashimoto,
  • Takao Fujisawa,
  • Mitsuho Imai,
  • Yoshiaki Nakamura,
  • Hideaki Bando,
  • Angelo Pirozzi,
  • Binbin Zheng-Lin,
  • Oluseyi Abidoye,
  • Cody R. Eslinger,
  • Mohamad Bassam Sonbol,
  • Hani Babiker,
  • Nguyen Tran,
  • Chigusa Morizane,
  • John H. Strickler,
  • Takayuki Yoshino,
  • Tanios Bekaii-Saab,
  • Masafumi Ikeda

摘要

Background

TP53 mutations are among the most frequent alterations in biliary tract cancer (BTC), but their prognostic relevance and predictive value for immune checkpoint inhibitors (ICI) remain unclear. We assessed clinico-molecular features, prognosis, and ICI efficacy by TP53 status in advanced BTC.

Methods

Patients with advanced BTC from Japan and the United States who underwent tissue- or plasma-based next-generation sequencing were retrospectively analyzed. Tissue-based sequencing was used for the primary analysis, and plasma ctDNA sequencing was evaluated as an exploratory cohort. Outcomes were compared between TP53 wild-type (WT) and TP53-mutated groups. Treatment–TP53 interactions for non-ICI versus ICI-containing regimens were assessed using multivariable Cox models. Whole-transcriptome sequencing data were analyzed using TIDE and Hallmark gene set enrichment analysis.

Results

Among 336 patients in the tissue-based cohort, 177 (52.7%) had TP53-mutated tumors. SMAD4, ERBB2, PTEN and CCNE1 co-alterations were enriched in TP53-mutated tumors, whereas IDH1, BAP1, and FGFR2 fusions were more frequent in WT tumors. TP53 mutations were independently associated with shorter PFS, whereas OS showed a similar but nonsignificant trend (PFS: HR 1.32, P = 0.04; OS: HR 1.32, P = 0.09). TP53 mutations were associated with shorter PFS in the non-ICI cohort but numerically longer PFS in the ICI cohort, with a significant treatment–TP53 interaction for PFS (P < 0.01). Similar trends were observed in the plasma cohort. Transcriptomic analyses (n = 59; all MSS) showed lower TIDE scores in TP53-mutated tumors.

Conclusion

TP53 mutations were associated with poor prognosis and may predict greater benefit from ICI, supporting biomarker-driven stratification.