Fang Xidong, Liu Mengxiao, Ren Qian, Li Renpeng, Wu Guozhi, Yuan Hao, Zheng Ya, Gou Xi, Wang Yuping, Zhou Yongning
The First Clinical Medical College, Lanzhou University, Lanzhou, China.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
Sci Rep. 2025 May 25;15(1):18231. doi: 10.1038/s41598-025-02745-x.
Gastric cancer (GC) constitutes a significant global public health burden due to its high morbidity rates and poor prognosis, underscoring the critical need for identifying novel therapeutic targets and elucidating their mechanisms. As a key member of the lanthionine synthetase C-like enzyme family, LANCL2 has shown aberrant expression in multiple malignancies. However, its biological significance in GC remains unclear. To this end, a series of exploration and research were conducted. Through integrated analyses of multi-omics databases and experimental validation, LANCL2 was up-regulated in STAD at both mRNA and protein levels. Moreover, elevated LANCL2 is closely associated with poor prognosis, and the constructed nomogram exhibited reliable predictive performance for 1, 3, and 5-year overall survival (OS) in the GC cohort. In addition, the genetic alteration status of LANCL2 was associated with new neoplasm event post initial therapy indicator, MSIsensor score, tumor mutation burden (TMB), and survival prognosis. Functional enrichment analysis indicated that LANCL2 is primarily associated with the regulation of immune checkpoints, the cell cycle and DNA repair. Furthermore, the expression of LANCL2 displayed significant correlations with immune infiltration, m6A methylation, ferroptosis, tumor cell stemness and drug reactivity. Finally, in vitro studies confirmed that silencing or overexpression of LANCL2 can significantly influence the changes of proliferation and cell cycle of GC cells. Overall, this study indicated LANCL2 as a critical regulator in GC pathogenesis, and highlighted its potential as a prognostic biomarker for gastric cancer management.
由于胃癌（GC）发病率高且预后差，它构成了重大的全球公共卫生负担，这凸显了识别新治疗靶点并阐明其机制的迫切需求。作为羊毛硫氨酸合成酶C样酶家族的关键成员，LANCL2在多种恶性肿瘤中均表现出异常表达。然而，其在胃癌中的生物学意义仍不清楚。为此，进行了一系列探索性研究。通过对多组学数据库的综合分析和实验验证，发现LANCL2在胃腺癌（STAD）的mRNA和蛋白质水平均上调。此外，LANCL2升高与预后不良密切相关，构建的列线图对胃癌队列中的1年、3年和5年总生存期（OS）具有可靠的预测性能。此外，LANCL2的基因改变状态与初始治疗后新肿瘤事件指标、微卫星不稳定性（MSI）检测评分、肿瘤突变负荷（TMB）和生存预后相关。功能富集分析表明，LANCL2主要与免疫检查点调节、细胞周期和DNA修复有关。此外，LANCL2的表达与免疫浸润、m6A甲基化、铁死亡、肿瘤细胞干性和药物反应性显著相关。最后，体外研究证实，沉默或过表达LANCL2可显著影响胃癌细胞增殖和细胞周期的变化。总体而言，本研究表明LANCL2是胃癌发病机制中的关键调节因子，并突出了其作为胃癌管理预后生物标志物的潜力。
