Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma.
Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma.
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DOI：
10.1007/s00262-020-02691-9
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Luo RZ
中科院分区：
文献类型：
--
作者：
Liu LL;Zhang SW;Chao X;Wang CH;Yang X;Zhang XK;Wen YL;Yun JP;Luo RZ
肝细胞癌（HCC）的“大小梁-块状”（MTM）模式被认为代表了一种独特的HCC亚型，并与特定的分子特征相关。由于HCC的免疫微环境是异质的，因此评估这种新变异的免疫微环境是很重要的。CMTM6是PD-L1的关键调节因子，是一种重要的免疫检查点抑制剂。本研究旨在探讨CMTM6/PD-L1共表达对HCC预后的影响及其与炎症细胞的关系。我们分析了619例HCC患者，并将肿瘤分为MTM和非MTM亚型。免疫组化法检测肿瘤细胞和炎症细胞中CMTM6和PD-L1的表达水平。计算癌细胞巢内炎性细胞密度。MTM型肿瘤PD-L1表达和炎症细胞密度高于非MTM型。在整个HCC患者群体和MTM HCC患者群体中，cmtm6高表达比cmtm6低表达与更短的OS和DFS显著相关。此外，CMTM6/PD-L1共表达的MTM HCC患者HCC进展和死亡的风险更高。此外，CMTM6/PD-L1共表达被证明与炎症细胞的高密度有关。值得注意的是，一种基于CMTM6/PD-L1共表达和炎症细胞的新的免疫分类成功地对MTM HCC的OS和DFS进行了分层。CMTM6/PD-L1共表达对HCC患者，尤其是MTM HCC患者的预后有不良影响。我们的研究为MTM HCC患者免疫状态评估联合抗cmtm6和抗pd - l1治疗提供了证据。本文的在线版本（10.1007/s00262-020-02691-9）包含补充材料，仅供授权用户使用。
The “macrotrabecular-massive” (MTM) pattern of hepatocellular carcinoma (HCC) has been suggested to represent a distinct HCC subtype and is associated with specific molecular features. Since the immune microenvironment is heterogenous in HCC, it is important to evaluate the immune microenvironment of this novel variant. CMTM6, a key regulator of PD-L1, is an important immunocheckpoint inhibitor. This study aimed to evaluate the prognostic effect of CMTM6/PD-L1 coexpression and its relationship with inflammatory cells in HCC. We analyzed 619 HCC patients and tumors were classified into MTM and non-MTM HCC subtypes. The expression levels of CMTM6 and PD-L1 in tumor and inflammatory cells were evaluated by immunohistochemistry. The density of inflammatory cells in the cancer cell nest was calculated. Tumoral PD-L1 expression and inflammatory cell density were higher in the MTM type than in the non-MTM type. CMTM6-high expression was significantly associated with shorter OS and DFS than CMTM6-low expression in the whole HCC patient population and the MTM HCC patient population. Moreover, MTM HCC patients with CMTM6/PD-L1 coexpression experienced a higher risk of HCC progression and death. In addition, CMTM6/PD-L1 coexpression was shown to be related to a high density of inflammatory cells. Notably, a new immune classification, based on CMTM6/PD-L1 coexpression and inflammatory cells, successfully stratified OS and DFS in MTM HCC. CMTM6/PD-L1 coexpression has an adverse effect on the prognosis of HCC patients, especially MTM HCC patients. Our study provides evidence for the combination of immune status assessment with anti-CMTM6 and anti-PD-L1 therapy in MTM HCC patients. The online version of this article (10.1007/s00262-020-02691-9) contains supplementary material, which is available to authorized users.
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影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
影响因子：
5.6
作者：
Wang, Hui;Gao, Jinping;Wang, Haiyong
通讯作者：
Wang, Haiyong
影响因子：
64.8
作者：
Burr ML;Sparbier CE;Chan YC;Williamson JC;Woods K;Beavis PA;Lam EYN;Henderson MA;Bell CC;Stolzenburg S;Gilan O;Bloor S;Noori T;Morgens DW;Bassik MC;Neeson PJ;Behren A;Darcy PK;Dawson SJ;Voskoboinik I;Trapani JA;Cebon J;Lehner PJ;Dawson MA
通讯作者：
Dawson MA
CMTM家族基因多态性与广西肝癌的相关性。
影响因子：
3.1
作者：
Bei, Chunhua;Tan, Chao;Tan, Shengkui
通讯作者：
Tan, Shengkui
影响因子：
2.7
作者：
Gao, Feng;Chen, Jing;Ji, Yong
通讯作者：
Ji, Yong