Background

Previous studies indicate that the splicing process, regulated by the cellular machinery of tumors (spliceosome), undergoes alterations, leading to oncogenic splicing events associated with the progression of tumors towards aggressiveness. However, the role of serine/arginine-rich splicing factor 7 (SRSF7) in hepatocellular carcinoma (HCC) and the tumor microenvironment (TME) remains unclear.

Methods

This study was aimed to explore the role and clinical significance of SRSF7 in HCC. By conducting functional analysis and gene set enrichment analysis, it was discovered that SRSF7 contributes to multiple pathways associated with immune response and tumor advancement. Further experiments verified that silencing of SRSF7 obviously inhibits progression of HCC.

Results

Aberrant expression of SRSF7, which were referred as an independent prognostic risk factor, effectively predicts the prognosis of patients with HCC. Functional and gene enrichment analyses revealed that SRSF7 is linked with multiple immune and tumor progression-related pathways, including the B cell receptor signaling pathway, positive regulation of leukocyte and immunoglobulin receptor binding cell activation, nuclear division, membrane invagination, cell cycle, as well as mTOR signaling pathway. Furthermore, increased SRSF7 expression was associated with tumor-infiltrating inflammatory cells (CD4+, monocytes/macrophages, CD8 + and endothelial). Additionally, multiple immune checkpoint genes were markedly positively related to SRSF7. The efficiency of SRSF7 in predicting immunomodulator and chemokine responses were also assessed in microenvironment. Moreover, in vitro analyses demonstrated that knockdown of SRSF7 suppressed the malignant evolution of HCC possibly by deactivating the PI3K/AKT/mTOR signaling.

Conclusion

The role of SRSF7 in the tumor microenvironment has been successfully assessed. It may be a valid bio-index for predicting the HCC prognosis, thereby guiding individualized immunotherapy for cancer.

中文翻译：

---

SRSF7 是肝细胞癌中一种有前景的预后生物标志物，并且与免疫浸润相关

背景

先前的研究表明，受肿瘤细胞机制（剪接体）调节的剪接过程发生改变，导致与肿瘤侵袭性进展相关的致癌剪接事件。然而，富含丝氨酸/精氨酸的剪接因子 7 (SRSF7) 在肝细胞癌 (HCC) 和肿瘤微环境 (TME) 中的作用仍不清楚。

方法

本研究旨在探讨SRSF7在HCC中的作用及临床意义。通过进行功能分析和基因集富集分析，发现SRSF7有助于与免疫反应和肿瘤进展相关的多种途径。进一步的实验证实，沉默SRSF7可以明显抑制HCC的进展。

结果

SRSF7的异常表达被称为独立的预后危险因素，可有效预测HCC患者的预后。功能和基因富集分析表明，SRSF7与多种免疫和肿瘤进展相关途径相关，包括B细胞受体信号途径、白细胞和免疫球蛋白受体结合细胞活化、核分裂、膜内陷、细胞周期的正向调节，以及作为 mTOR 信号通路。此外，SRSF7表达增加与肿瘤浸润炎症细胞（CD4+、单核细胞/巨噬细胞、CD8+和内皮细胞）相关。此外，多个免疫检查点基因与SRSF7显着正相关。还在微环境中评估了 SRSF7 在预测免疫调节剂和趋化因子反应方面的效率。此外，体外分析表明，SRSF7 的敲除可能通过停用 PI3K/AKT/mTOR 信号传导来抑制 HCC 的恶性进化。

结论

SRSF7 在肿瘤微环境中的作用已被成功评估。它可能是预测HCC预后的有效生物指标，从而指导癌症的个体化免疫治疗。