Characterisation of the immune-related transcriptome in resected biliary tract cancers.
Characterisation of the immune-related transcriptome in resected biliary tract cancers.
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DOI：
10.1016/j.ejca.2017.09.005
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Braconi C
中科院分区：
文献类型：
--
作者：
Ghidini M;Cascione L;Carotenuto P;Lampis A;Trevisani F;Previdi MC;Hahne JC;Said-Huntingford I;Raj M;Zerbi A;Mescoli C;Cillo U;Rugge M;Roncalli M;Torzilli G;Rimassa L;Santoro A;Valeri N;Fassan M;Braconi C
虽然已知胆道癌（BTC）具有炎症组分，但从未进行过免疫相关转录物的详细表征。在这些研究中，nCounter PanCancer免疫分析面板用于评估切除的BTC的肿瘤组织（TT）和匹配的邻近组织（AT）中770种免疫相关转录物的表达。使用考克斯回归分析和Kaplan-Meier方法将结果与无复发生存期（RFS）关联起来。在TT和AT的探索性集（n = 22）的第一次分析显示与T细胞活化相关的39个转录的失调。与TT相比，AT的复发风险与更多的基因失调相关。在整个集合（n = 53）的分析显示，AT细胞毒性T淋巴细胞抗原-4（CTLA 4）表达和RFS之间的相关性，在多变量分析中保持统计学显著性。CTLA 4表达与叉头框P3（FOXP3）表达相关，表明在T调节细胞中富集。已知CTLA4通过结合分化簇80（CD80）起作用。AT CD80表达与RFS之间无相关性。然而，CD80表达在接受辅助化疗的患者中分化预后。我们发现，免疫调节转录组在切除的BTCs中失调。我们的研究包括少数患者，无法得出明确的结论;然而，它提供了对潜在转录本的有用见解，可能值得在更大的患者队列中进一步研究。Nanostring数据已提交给GEO储存库：GSE 90698和GSE 90699。BTC具有免疫相关转录物的紊乱，其对细胞毒性T淋巴细胞抗原-4（CTLA 4）轴具有重要作用。CTLA4在肿瘤周围区域的表达与预后相关，是一个潜在的有希望的预后因素。我们的数据表明，免疫疗法可能对BTC产生影响，作为重新解决宿主对肿瘤免疫反应的一种手段。
Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan–Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. Nanostring data have been submitted to GEO repository: GSE90698 and GSE90699. BTCs harbour a derangement of immune-related transcripts with an important role for the cytotoxic T-lymphocyte antigen-4 (CTLA4) axis. CTLA4 expression in the peritumoural areas correlates with outcome and represents a potential promising prognostic factor. Our data suggest that immunotherapy may have an impact in BTCs as a mean to re-address the host immune response to the tumour.
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DOI：
10.1056/nejmoa1510764
发表时间：
2015-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sparano JA;Gray RJ;Makower DF;Pritchard KI;Albain KS;Hayes DF;Geyer CE Jr;Dees EC;Perez EA;Olson JA Jr;Zujewski J;Lively T;Badve SS;Saphner TJ;Wagner LI;Whelan TJ;Ellis MJ;Paik S;Wood WC;Ravdin P;Keane MM;Gomez Moreno HL;Reddy PS;Goggins TF;Mayer IA;Brufsky AM;Toppmeyer DL;Kaklamani VG;Atkins JN;Berenberg JL;Sledge GW
通讯作者：
Sledge GW
影响因子：
13.5
作者：
Braconi, Chiara;Huang, Nianyuan;Patel, Tushar
通讯作者：
Patel, Tushar
DOI：
10.1073/pnas.1600067113
发表时间：
2016-10-25
影响因子：
11.1
作者：
Guest, Rachel V.;Boulter, Luke;Forbes, Stuart J.
通讯作者：
Forbes, Stuart J.
影响因子：
--
作者：
Ozgur, Halil Hakan;Ercetin, Ayse Pinar;Aktas, Safiye
通讯作者：
Aktas, Safiye
影响因子：
3.7
作者：
Braconi C;Swenson E;Kogure T;Huang N;Patel T
通讯作者：
Patel T