Expression of CD22 in Triple-Negative Breast Cancer: A Novel Prognostic Biomarker and Potential Target for CAR Therapy.
Expression of CD22 in Triple-Negative Breast Cancer: A Novel Prognostic Biomarker and Potential Target for CAR Therapy.
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CD22 在三阴性乳腺癌中的表达：一种新型预后生物标志物和 CAR 治疗的潜在靶点
DOI：
10.3390/ijms24032152
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发表时间：
2023-01-21
影响因子：
5.6
通讯作者：
Wu, Jundong
中科院分区：
文献类型：
--
作者：
Zaib, Tahir;Cheng, Ke;Liu, Tingdang;Mei, Ruyi;Liu, Qin;Zhou, Xiaoling;He, Lifang;Rashid, Hibba;Xie, Qingdong;Khan, Hanif;Xu, Yien;Sun, Pingnan;Wu, Jundong
三阴性乳腺癌（TNBC）占所有乳腺癌病例的15-20%。由于缺乏众所周知的分子靶点[雌激素受体（ER）、孕酮受体（PR）和人表皮生长因子受体2（HER 2）]的表达，TNBC中需要更多的替代治疗方法。基于嵌合抗原受体（CAR）-T细胞的免疫治疗是近十年来治疗进展突出的最新治疗技术之一，尤其是在血液系统恶性肿瘤的治疗方面，但CAR-T细胞对实体瘤的治疗效果尚未显示出显著的临床获益。在实体瘤中识别高度特异性的CAR-T靶标对于其成功治疗也至关重要。据报道，CD 22是一种多功能受体，主要在成熟B细胞（淋巴细胞）表面表达，并且在大多数B细胞恶性肿瘤中也高度表达。本研究旨在探讨CD 22在TNBC中的表达。应用生物信息学方法分析CD 22在乳腺癌及正常组织中的表达。从The Cancer Genome Atlas（TCGA）下载正常和乳腺癌患者的RNA-seq数据，并使用R语言进行差异基因表达。此外，使用在线生物信息学网络工具（GEPIA和TNM plot）来评估乳腺癌和正常组织中CD 22的表达。进行蛋白质印迹（WB）分析和免疫荧光（IF）以表征TNBC细胞系中CD 22的表达。对来自97名TNBC患者的肿瘤标本进行免疫组织化学（IHC）染色以检测CD 22表达。此外，进行统计学分析以分析临床病理参数与CD 22表达的关联。同时对TNBC患者的总生存数据与CD 22表达进行相关性分析。TCGA数据的差异基因表达分析显示，与正常乳腺组织相比，CD 22是在乳腺癌中高表达的上调差异表达基因（DEG）之一。WB和IF分析显示，CD 22在TNBC细胞系中高表达。IHC结果还显示，约62.89%（61/97）的TNBC标本为CD 22染色阳性。23.71%（23/97）的TNBC标本CD 22呈胞膜表达，39.18%（38/97）的TNBC标本CD 22呈胞浆/胞膜表达，37.11%（36/97）的TNBC标本CD 22呈阴性表达。此外，在TNBC患者的肿瘤大小和CD 22表达之间发现了显著的相关性，这揭示了其作为预后生物标志物的潜力。TNBC患者的总生存率与CD 22表达之间无显著相关性。总之，我们首次证明了CD 22在TNBC中高度表达。基于我们的研究结果，我们预计CD 22可以用作TNBC的预后生物标志物，并且它可能是TNBC中的潜在CAR-T靶点，对于TNBC来说，几乎没有治疗选择。然而，更多的大规模研究和临床试验将确保其作为TNBC中CAR-T靶标的潜在有用性。
Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer cases. Due to the lack of expression of well-known molecular targets [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], there is a need for more alternative treatment approaches in TNBC. Chimeric antigen receptor (CAR)-T cell-based immunotherapy treatment is one of the latest treatment technologies with outstanding therapeutic advances in the past decade, especially in the treatment of hematologic malignancies, but the therapeutic effects of CAR-T cells against solid tumors have not yet shown significant clinical benefits. Identification of highly specific CAR-T targets in solid tumors is also crucial for its successful treatment. CD22 is reported to be a multifunctional receptor that is mainly expressed on the surface of mature B-cells (lymphocytes) and is also highly expressed in most B-cell malignancies. This study aimed to investigate the expression of CD22 in TNBC. Bioinformatic analysis was performed to evaluate the expression of CD22 in breast carcinoma and normal tissues. RNA-seq data of normal and breast carcinoma patients were downloaded from The Cancer Genome Atlas (TCGA), and differential gene expression was performed using R language. Additionally, online bioinformatics web tools (GEPIA and TNM plot) were used to evaluate the expression of CD22 in breast carcinoma and normal tissues. Western blot (WB) analysis and immunofluorescence (IF) were performed to characterize the expression of CD22 in TNBC cell lines. Immunohistochemical (IHC) staining was performed on tumor specimens from 97 TNBC patients for CD22 expression. Moreover, statistical analysis was performed to analyze the association of clinical pathological parameters with CD22 expression. Correlation analysis between overall survival data of TNBC patients and CD22 expression was also performed. Differential gene expression analysis of TCGA data revealed that CD22 is among the upregulated differentially expressed genes (DEGs) with high expression in breast cancer, as compared to normal breast tissues. WB and IF analysis revealed high expression of CD22 in TNBC cell lines. IHC results also showed that approximately 62.89% (61/97) of TNBC specimens were stained positive for CD22. Cell membrane expression of CD22 was evident in 23.71% (23/97) of TNBC specimens, and 39.18% (38/97) of TNBC specimens showed cytoplasmic/membrane expression, while 37.11% (36/97) specimens were negative for CD22. Furthermore, significant associations were found between the size of tumors in TNBC patients and CD22 expression, which unveils its potential as a prognostic biomarker. No significant correlation was found between the overall survival of TNBC patients and CD22 expression. In conclusion, we demonstrated for the first time that CD22 is highly expressed in TNBC. Based on our findings, we anticipated that CD22 could be used as a prognostic biomarker in TNBC, and it might be a potential CAR-T target in TNBC for whom few therapeutic options exist. However, more large-scale studies and clinical trials will ensure its potential usefulness as a CAR-T target in TNBC.
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影响因子：
7.2
作者：
Shah NN;Sokol L
通讯作者：
Sokol L
影响因子：
6.2
作者：
Rimawi, Mothaffar F.;Shetty, Priya B.;Weiss, Heidi L.;Schiff, Rachel;Osborne, C. Kent;Chamness, Gary C.;Elledge, Richard M.
通讯作者：
Elledge, Richard M.
DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
影响因子：
3.8
作者：
Malorni L;Shetty PB;De Angelis C;Hilsenbeck S;Rimawi MF;Elledge R;Osborne CK;De Placido S;Arpino G
通讯作者：
Arpino G
影响因子：
3.8
作者：
Tchou J;Wang LC;Selven B;Zhang H;Conejo-Garcia J;Borghaei H;Kalos M;Vondeheide RH;Albelda SM;June CH;Zhang PJ
通讯作者：
Zhang PJ