研究动态
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食管鳞状细胞癌中免疫相关表达谱与化疗敏感性的关联性。

Association of immune-related expression profile with sensitivity to chemotherapy in esophageal squamous cell carcinoma.

发表日期:2023 Sep 15
作者: Yoshiyuki Tsukamoto, Shusaku Kurogi, Hajime Fujishima, Tomotaka Shibata, Shoichi Fumoto, Kohei Nishiki, Kosuke Suzuki, Tsuyoshi Etoh, Norio Shiraishi, Takafumi Fuchino, Yuka Hirashita, Chisato Nakada, Tomohisa Uchida, Masafumi Inomata, Masatsugu Moriyama, Naoki Hijiya
来源: Immunity & Ageing

摘要:

新辅助化疗(NAC)接着手术是日本对于局部晚期食管癌患者的标准治疗方法之一。最近,JCOG1109研究揭示了使用docetaxel,顺铂和5-氟尿嘧啶(5-FU)(DCF-NAC)的NAC优于使用顺铂和5-FU的NAC,现已成为标准的术前化疗方案。我们以前使用微阵列系统对DCF-NAC前(preNAC)的食管鳞状细胞癌(ESCC)患者的内镜活检样本进行了表达谱分析,并鉴定出了17个分子作为DCF-NAC的病理完全缓解的预测生物标志物。在本研究中,我们根据组织病理反应等级重新分组我们以前的数据集,并加入了一些微阵列配置文件,并使用包括DAVID,GSEA,UALCAN和CIBERSORTx在内的生物信息学网络工具进行了再分析。我们发现,在高度耐药组和敏感组之间有204个基因表达差异。其中一些基因表达差异基因(DEGs)与免疫反应有关,并在敏感组中呈高表达。UALCAN显示,前50个DEGs中有28个高表达与良好预后相关(p<0.25),其中18个达到了显著水平(p<0.05),表明这些基因高表达的患者可能从化疗中获益并且具有更好的预后。在DCF敏感病例的preNAC活检组织中,我们证明了表达CXCL9的mRNA的细胞的存在,CXCL9是与预后相关的DEGs之一。我们的结果突出了preNAC ESCC中与免疫相关的表达谱与DCF-NAC疗效之间的关联。© 2023 The Authors. Cancer Science由澳大利亚John Wiley & Sons Ltd代表日本癌症协会发表。
Neoadjuvant chemotherapy (NAC) followed by surgery is one of the standard therapeutic approaches in Japan for patients with locally advanced esophageal carcinoma. Recently, the JCOG1109 study revealed that NAC with docetaxel, cisplatin and 5-fluorouracil (5-FU) (DCF-NAC) is superior to NAC with cisplatin and 5-FU, and has now become the standard preoperative chemotherapy. Using a microarray system, we have previously investigated the expression profiles of endoscopic biopsy samples from patients with esophageal squamous cell carcinoma (ESCC) before DCF-NAC (preNAC) and identified 17 molecules as biomarkers predictive of a pathologically complete response to DCF-NAC. Here, we re-grouped our previous dataset based on the histopathological response grade with the addition of several microarray profiles and conducted a re-analysis using bioinformatic web tools including DAVID, GSEA, UALCAN, and CIBERSORTx. We identified 204 genes that were differentially expressed between the highly resistant and sensitive groups. Some of these differentially expressed genes (DEGs) were related to the immune response and showed higher expression in the sensitive group. UALCAN showed that high expression of 28 of the top 50 DEGs was associated with a favorable prognosis (p < 0.25), and that this reached a significant (p < 0.05) level for 18 of them, suggesting that patients with high expression of these genes might have benefited from chemotherapy and thus had a better outcome. In preNAC biopsy tissues from a DCF-sensitive case, we demonstrated the presence of cells expressing mRNA for CXCL9, one of the prognosis-related DEGs. Our results highlight the association of immune-related expression profile in preNAC ESCC with the DCF-NAC efficacy.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.