鉴定 HM13 作为肝细胞癌免疫治疗的预后指标和预测生物标志物。

Identification of HM13 as a prognostic indicator and a predictive biomarker for immunotherapy in hepatocellular carcinoma.

机构信息

Department of Blood transfusion, Zhengzhou University First Affiliated Hospital, Zhengzhou, China.

Department of Medical Laboratory, Zhengzhou University First Affiliated Hospital, Zhengzhou, China.

出版信息

BMC Cancer. 2022 Aug 13;22(1):888. doi: 10.1186/s12885-022-09987-2.

BACKGROUND

Histocompatibility minor 13 (HM13) is a signal sequence stubbed intramembrane cleavage catalytic protein that is essential for cell signaling, intracellular communication, and cancer. However, the expression of HM13 and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in the microenvironment, and potential to predict immunotherapeutic response in HCC are unknown.

METHODS

The HM13 expression, clinicopathology analysis, and its influence on survival were analyzed in multiple public databases and further verified in collected HCC and normal tissues by qRT-PCR and immunohistochemistry staining assay (IHC). Furthermore, the lentivirus vector encoding HM13-shRNA to manipulate HM13 expression was selected to investigate whether HM13 could influence the malignant growth and metastasis potential of HCC cells. Finally, significant impacts of HM13 on the HCC tumor microenvironment (TME) and reaction to immune checkpoint inhibitors were analyzed.

RESULTS

Upregulated HM13 was substantially correlated with poor prognosis in patients with HCC, and could facilitate the proliferation and migratory potential of HCC cells. Additionally, patients with high HM13 expression might be more sensitive to immunotherapy.

CONCLUSIONS

HM13 might be a prognostic biomarker and potential molecular therapeutic target for HCC.

背景

组织相容性次要 13 号（HM13）是一种信号序列截短的跨膜切割催化蛋白，对细胞信号转导、细胞内通讯和癌症至关重要。然而，HM13 的表达及其预后价值、与肿瘤浸润免疫细胞（TIICs）在微环境中的关联以及预测 HCC 免疫治疗反应的潜力尚不清楚。

方法

在多个公共数据库中分析了 HM13 的表达、临床病理分析及其对生存的影响，并通过 qRT-PCR 和免疫组织化学染色（IHC）进一步验证了收集的 HCC 和正常组织中的 HM13。此外，选择了编码 HM13-shRNA 的慢病毒载体来操纵 HM13 的表达，以研究 HM13 是否可以影响 HCC 细胞的恶性生长和转移潜力。最后，分析了 HM13 对 HCC 肿瘤微环境（TME）和免疫检查点抑制剂反应的显著影响。