Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 in TP53-Aberrant Triple-Negative Breast Cancer.
Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 in TP53-Aberrant Triple-Negative Breast Cancer.
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CSPG4 和 PDL1 在 TP53 异常三阴性乳腺癌中的共表达及其联合预后价值
DOI：
10.3389/fonc.2022.804466
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发表时间：
2022
影响因子：
4.7
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Hu ZY;Zheng C;Yang J;Ding S;Tian C;Xie N;Xue L;Wu M;Fu S;Rao Z;Price MA;McCarthy JB;Ouyang Q;Lin J;Deng X
在三阴性乳腺癌（TNBC）中，PDL 1/PD 1定向免疫疗法在不到20%的患者中有效。在我们的初步研究中，我们发现CSPG 4与PDL 1在TNBC中高度表达，特别是那些携带TP 53畸变的TNBC。然而，在TNBC中共表达CSPG 4和PDL 1的临床意义仍然难以捉摸。共招募了2017年1月至2019年8月期间在湖南省肿瘤医院接受治疗的85例晚期TNBC患者。采用免疫组化（IHC）法检测CSPG 4和PDL 1在TNBC组织中的表达。进一步使用来自TCGA-BRCA项目的RNA-seq数据集分析TP 53异常TNBC中CSPG 4和PDL 1的mRNA表达。采用考克斯比例风险模型和Kaplan-Meier曲线结合Logrank检验分析CSPG 4和PDL 1对生存的影响。TNBC细胞系进一步用于研究所涉及的分子机制。 TP 53畸变发生在超过50%的转移性TNBC中，并且与较高的肿瘤突变负荷（TMB）相关。在TCGA-BRCA RNA-seq数据集分析中，CSPG 4和PDL 1水平在TNBC中均较高，尤其是在TP 53异常的TNBC中。免疫组化结果显示，近60%的晚期TNBC为CSPG 4阳性，约25%为CSPG 4阳性和PDL 1阳性。如通过流式细胞术和免疫印迹所揭示的，与非TNBC细胞相比，CSPG 4和PDL 1的水平在TNBC细胞系中较高。单因素考克斯回归分析表明，CSPG 4阳性是转移性TNBC无进展生存期的重要危险因素，风险比（HR）为2.26（P = 0.05）。对数秩检验的KM曲线也将高水平的CSPG 4确定为TCGA-BRCA样本中晚期乳腺癌总生存率的显著风险因素（P = 0.02）。免疫印迹分析表明，EMT相关途径参与CSPG 4介导的侵袭。CSPG 4表达水平与TP 53异常TNBC细胞中的PDL 1阳性相关。CSPG 4表达的患者治疗反应差，总生存率低。CSPG 4和PDL 1共表达可能具有重要的预后价值，并为TNBC患者提供新的治疗靶点。CSPG 4可能通过EMT相关通路介导肿瘤侵袭和PDL 1过表达。
In triple-negative breast cancer (TNBC), PDL1/PD1-directed immunotherapy is effective in less than 20% of patients. In our preliminary study, we have found CSPG4 to be highly expressed together with PDL1 in TNBCs, particularly those harboring TP53 aberrations. However, the clinical implications of co-expressed CSPG4 and PDL1 in TNBCs remain elusive. A total of 85 advanced TNBC patients treated in the Hunan Cancer Hospital between January 2017 and August 2019 were recruited. The expressions of CSPG4 and PDL1 in TNBC tissues were investigated using immunohistochemistry (IHC). The RNA-seq dataset from the TCGA-BRCA project was further used to analyze the mRNA expression of CSPG4 and PDL1 in TP53-aberrant TNBCs. Cox proportional hazards model and Kaplan–Meier curves with Logrank test was used to analyze the effects of CSPG4 and PDL1 on survival. TNBC cell lines were further used to investigate the molecular mechanism that were involved. TP53 aberrations occurred in more than 50% of metastatic TNBCs and were related to higher tumor mutation burden (TMB). In TCGA-BRCA RNA-seq dataset analysis, both CSPG4 and PDL1 levels were high in TNBCs, especially in TP53-aberrant TNBCs. IHC assay showed nearly 60% of advanced TNBCs to be CSPG4-positive and about 25% to be both CSPG4-positive and PDL1-positive. The levels of CSPG4 and PDL1 were high in TNBC cell lines as revealed by flow cytometry and immunoblotting compared with non-TNBC cells. Univariate Cox regression analysis indicated that CSPG4 positivity was a significant risk factor for progression-free survival in metastatic TNBCs, with a hazard ratio (HR) of 2.26 (P = 0.05). KM curves with Logrank test also identified high level of CSPG4 as a significant risk factor for overall survival in advanced breast cancers in TCGA-BRCA samples (P = 0.02). The immunoblotting assays showed that EMT-related pathways were involved in CSPG4-mediated invasion. CSPG4 expression level is associated with PDL1 positivity in TP53-aberrant TNBC cells. Patients with CSPG4 expression have poor treatment response and poor overall survival. Co-expressed CSPG4 and PDL1 may have an important prognostic value and provide new therapeutic targets in TNBC patients. CSPG4 might mediate tumor invasion and PDL1 overexpression through EMT-related pathway.
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影响因子：
7.3
作者：
Gao C;Li H;Liu C;Xu X;Zhuang J;Zhou C;Liu L;Feng F;Sun C
通讯作者：
Sun C
DOI：
10.1186/bcr3147
发表时间：
2012-03-15
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Knappskog S;Chrisanthar R;Løkkevik E;Anker G;Østenstad B;Lundgren S;Risberg T;Mjaaland I;Leirvaag B;Miletic H;Lønning PE
通讯作者：
Lønning PE
影响因子：
50.5
作者：
Ali, H. R.;Glont, S. -E.;Caldas, C.
通讯作者：
Caldas, C.
DOI：
10.1073/pnas.93.18.9710
发表时间：
1996-09-03
影响因子：
11.1
作者：
Pluschke, G;Vanek, M;Reisfeld, RA
通讯作者：
Reisfeld, RA
影响因子：
--
作者：
Salvianti F;Rotunno G;Galardi F;De Luca F;Pestrin M;Vannucchi AM;Di Leo A;Pazzagli M;Pinzani P
通讯作者：
Pinzani P