CD44 is a potential immunotherapeutic target and affects macrophage infiltration leading to poor prognosis

作者全名："Liu, Shuangqing; Liu, Zehan; Shang, Aichen; Xun, Jing; Lv, Zongjing; Zhou, Siying; Liu, Cui; Zhang, Qi; Yang, Yuming"

作者地址："[Liu, Shuangqing; Liu, Zehan; Shang, Aichen; Lv, Zongjing; Zhou, Siying; Liu, Cui; Zhang, Qi; Yang, Yuming] Tianjin Med Univ, Nankai Hosp, Tianjin 300070, Peoples R China; [Liu, Zehan] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Dept Gen Surg, Sect HepatoPancreatoBiliary Surg,Affiliated Hosp, Chengdu 610031, Peoples R China; [Liu, Zehan] Chongqing Med Univ, Affiliated Hosp Chengdu 2, Chengdu 610031, Peoples R China; [Shang, Aichen] Tianjin Med Univ, Sino Singapore Ecoc Hosp, Dept Pathol, Tianjin 300456, Peoples R China; [Xun, Jing; Zhang, Qi] Tianjin Nankai Hosp, Inst Acute Abdominal Dis, Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin, Peoples R China; [Yang, Yuming] Tianjin Nankai Hosp, Dept Pathol, Tianjin, Peoples R China"

通信作者："Zhang, Q; Yang, YM (通讯作者)，Tianjin Med Univ, Nankai Hosp, Tianjin 300070, Peoples R China.; Zhang, Q (通讯作者)，Tianjin Nankai Hosp, Inst Acute Abdominal Dis, Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin, Peoples R China.; Yang, YM (通讯作者)，Tianjin Nankai Hosp, Dept Pathol, Tianjin, Peoples R China."

来源：SCIENTIFIC REPORTS

ESI学科分类：Multidisciplinary

WOS号：WOS:001010888200030

JCR分区：Q1

影响因子：3.8

年份：2023

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："CD44 plays a key role in the communication of CSCs with the microenvironment and the regulation of stem cell properties. UALCAN was used to analyze the expression of CD44 in bladder cancer (BLCA) and normal tissue. The UALCAN was utilized to analyze the prognostic value of CD44 in BLCA. The TIMER database was used to explore the relationship between CD44 and PD-L1; CD44 and tumor-infiltrating immune cells. The regulatory effect of CD44 on PD-L1 was verified by cell experiments in vitro. IHC confirmed the results of the bioinformatics analysis. GeneMania and Metascape were used to analyze protein-protein interaction (PPI) investigations and functional enrichment analysis. We found that BLCA patients with high CD44 expression had worse survival than those with low CD44 expression (P < 0.05). IHC and the TIMER database results showed that CD44 expression was positively correlated with PD-L1 expression (P < 0.05). At the cellular level, the expression of PD-L1 was significantly inhibited after CD44 expression was inhibited by siRNA. Immune infiltration analysis showed that CD44 expression levels in BLCA were significantly correlated with immune infiltration levels of different immune cells. IHC staining results further confirmed that the expression of CD44 in tumor cells was positively associated with the number of CD68(+) macrophages and CD163(+) macrophages (P < 0.05). Our results suggest that CD44 is a positive regulator of PD-L1 in BLCA and may be a key regulator of tumor macrophages infiltration and may be involved in M2 macrophage polarization. Our study provided new insights into the prognosis and immunotherapy of BLCA patients through macrophage infiltration and immune checkpoints."

基金机构：Horizontal Project of Tianjin Nankai Hospital [NKYY-2022-003]; National Natural Science Foundation of China [82170887]

基金资助正文：This study was supported by Horizontal Project of Tianjin Nankai Hospital: NKYY-2022-003 and the National Natural Science Foundation of China (NO. 82170887).