Ren Yanbing, Mao Ying, Yuan Xiao
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, PR China.
Anhui Public Health Clinical Center, Hefei, Anhui, PR China.
Histol Histopathol. 2025 Sep;40(9):1435-1446. doi: 10.14670/HH-18-857. Epub 2024 Dec 2.
High levels of histocompatibility minor 13 (HM13) have been related to the progression of several cancers. Here, we investigated the function of HM13 in colorectal cancer (CRC).
HM13 expression, clinicopathology analysis, and its influence on survival were analyzed in multiple public databases (TCGA, TIMER2.0, and GEPIA). HM13 mRNA and protein levels in CRC cells were examined by qRT-PCR and western blot, respectively. CCK-8, Transwell, wound-healing, and adhesion assays were used to measure cell proliferation, migration, invasion, and adhesion in HM13-overexpressed and -silenced cells. The relationship between HM13 expression and neutrophil infiltration was also analyzed. CRC xenograft mouse models were used for verification of HM13 function.
In this study, TCGA dataset analysis revealed that elevated HM13 levels correlated with malignant progression and worse survival outcomes in CRC. Cell migration, proliferation, invasion, and adhesion were suppressed through the knockdown of sh-HM13 and enhanced through HM13 overexpression. Additionally, HM13 expression significantly correlated with the infiltration level of neutrophils in CRC in TCGA and TIMER analyses. HM13 levels were also positively correlated with myeloperoxidase (MPO) levels. In addition, studies further confirmed that MPO overexpression partially abolished the inhibition of tumor growth by sh-HM13 in CRC.
The results suggested that high HM13 expression in CRC could promote tumor growth and metastasis by reducing neutrophil infiltration and may serve as a useful target in the treatment of metastatic CRC.
高水平的组织相容性次要抗原13(HM13)与多种癌症的进展相关。在此,我们研究了HM13在结直肠癌(CRC)中的作用。
在多个公共数据库(TCGA、TIMER2.0和GEPIA)中分析HM13表达、临床病理分析及其对生存的影响。分别通过qRT-PCR和蛋白质印迹法检测CRC细胞中HM13的mRNA和蛋白质水平。使用CCK-8、Transwell、伤口愈合和黏附实验来检测过表达和沉默HM13的细胞的增殖、迁移、侵袭和黏附能力。还分析了HM13表达与中性粒细胞浸润之间的关系。使用CRC异种移植小鼠模型验证HM13的功能。
在本研究中,TCGA数据集分析显示,CRC中HM13水平升高与恶性进展和较差的生存结果相关。通过敲低sh-HM13可抑制细胞迁移、增殖、侵袭和黏附,而过表达HM13则增强这些能力。此外,在TCGA和TIMER分析中,HM13表达与CRC中中性粒细胞的浸润水平显著相关。HM13水平也与髓过氧化物酶(MPO)水平呈正相关。此外,研究进一步证实,MPO过表达部分消除了sh-HM13对CRC肿瘤生长的抑制作用。
结果表明,CRC中高表达的HM13可通过减少中性粒细胞浸润促进肿瘤生长和转移,可能是转移性CRC治疗的一个有用靶点。