Abstract：
BACKGROUND: Altered expression and activity of solute carrier family 4 member 4 (SLC4A4) could affect the growth, survival and metastasis of tumor cells. Currently, the role of SLC4A4 in lung adenocarcinoma (LUAD) immunotherapy and prognosis was not entirely clear.
METHODS: We analyzed SLC4A4 expression in LUAD tissues and cell lines using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. The effects of SLC4A4 overexpression on angiogenesis, cell migration, invasion, and epithelial-mesenchymal transition were examined. Public databases helped construct a risk model evaluating SLC4A4\'s expression on LUAD prognosis and immunotherapy response. Additionally, a xenograft model, flow cytometry, and enzyme-linked immunosorbent assay further explored SLC4A4\'s role in tumor immune microenvironment infiltration.
RESULTS: Upregulation of SLC4A4 promoted apoptosis in the LUAD cell line and significantly inhibited the migration and invasive ability of cancer cells (P<0.01). A total of 10 key genes (including SIGLEC6, RHOV, PIR, MOB3B, MIR3135B, LPAR6, KRT8, ITGA2, CPS1, and C6) were screened according to SLC4A4 expression, immune score and stromal score, and a prognostic model with good outcome was constructed (AUC values of which in the training cohort at 1,3, and 5 years reached 0.73, 0.73, and 0.72, respectively). Importantly, we demonstrated that high expression of SLC4A4 was able to increase the proliferation level and cytokine secretion of CD8+ T cells for the purpose of promoting the immune system response to LUAD.
CONCLUSIONS: Our study revealed that SLC4A4 can serve as a prognostic indicator for LUAD, providing new insights into the treatment and diagnosis of LUAD.
METHODS: We analyzed SLC4A4 expression in LUAD tissues and cell lines using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. The effects of SLC4A4 overexpression on angiogenesis, cell migration, invasion, and epithelial-mesenchymal transition were examined. Public databases helped construct a risk model evaluating SLC4A4\'s expression on LUAD prognosis and immunotherapy response. Additionally, a xenograft model, flow cytometry, and enzyme-linked immunosorbent assay further explored SLC4A4\'s role in tumor immune microenvironment infiltration.
RESULTS: Upregulation of SLC4A4 promoted apoptosis in the LUAD cell line and significantly inhibited the migration and invasive ability of cancer cells (P<0.01). A total of 10 key genes (including SIGLEC6, RHOV, PIR, MOB3B, MIR3135B, LPAR6, KRT8, ITGA2, CPS1, and C6) were screened according to SLC4A4 expression, immune score and stromal score, and a prognostic model with good outcome was constructed (AUC values of which in the training cohort at 1,3, and 5 years reached 0.73, 0.73, and 0.72, respectively). Importantly, we demonstrated that high expression of SLC4A4 was able to increase the proliferation level and cytokine secretion of CD8+ T cells for the purpose of promoting the immune system response to LUAD.
CONCLUSIONS: Our study revealed that SLC4A4 can serve as a prognostic indicator for LUAD, providing new insights into the treatment and diagnosis of LUAD.
摘要：
背景：溶质载体家族4成员4（SLC4A4）的表达和活性改变可能会影响生长，肿瘤细胞的存活和转移。目前,SLC4A4在肺腺癌(LUAD)免疫治疗和预后中的作用尚不完全清楚.
方法：我们使用定量逆转录-聚合酶链反应分析了SLC4A4在LUAD组织和细胞系中的表达，西方印迹,和免疫组织化学。SLC4A4过表达对血管生成的影响,细胞迁移，入侵,并检查上皮-间质转化。公共数据库帮助构建了评估SLC4A4表达对LUAD预后和免疫治疗反应的风险模型。此外,异种移植模型,流式细胞术,酶联免疫吸附试验进一步探讨了SLC4A4在肿瘤免疫微环境浸润中的作用。
结果：上调SLC4A4可促进LUAD细胞株的凋亡，并显著抑制癌细胞的迁移和侵袭能力（P<0.01）。共有10个关键基因(包括SIGLEC6、RHOV、PIR,MOB3B,MIR3135B,LPAR6，KRT8，ITGA2，CPS1和C6）根据SLC4A4表达进行筛选，免疫评分和基质评分，并构建了预后良好的预后模型(在1,3和5年的训练队列中AUC值分别达到0.73,0.73和0.72).重要的是,我们证明SLC4A4的高表达能够增加CD8+T细胞的增殖水平和细胞因子分泌，以促进免疫系统对LUAD的反应。
结论：我们的研究表明，SLC4A4可以作为LUAD的预后指标，为LUAD的治疗和诊断提供新的见解。
方法：我们使用定量逆转录-聚合酶链反应分析了SLC4A4在LUAD组织和细胞系中的表达，西方印迹,和免疫组织化学。SLC4A4过表达对血管生成的影响,细胞迁移，入侵,并检查上皮-间质转化。公共数据库帮助构建了评估SLC4A4表达对LUAD预后和免疫治疗反应的风险模型。此外,异种移植模型,流式细胞术,酶联免疫吸附试验进一步探讨了SLC4A4在肿瘤免疫微环境浸润中的作用。
结果：上调SLC4A4可促进LUAD细胞株的凋亡，并显著抑制癌细胞的迁移和侵袭能力（P<0.01）。共有10个关键基因(包括SIGLEC6、RHOV、PIR,MOB3B,MIR3135B,LPAR6，KRT8，ITGA2，CPS1和C6）根据SLC4A4表达进行筛选，免疫评分和基质评分，并构建了预后良好的预后模型(在1,3和5年的训练队列中AUC值分别达到0.73,0.73和0.72).重要的是,我们证明SLC4A4的高表达能够增加CD8+T细胞的增殖水平和细胞因子分泌，以促进免疫系统对LUAD的反应。
结论：我们的研究表明，SLC4A4可以作为LUAD的预后指标，为LUAD的治疗和诊断提供新的见解。
