• Hang Chen, Shuguang Xu, Zeyang Hu, Yiqing Wei, Youjie Zhu, Shenzhe Fang, Qiaoling Pan, Kaitai Liu, Ni Li, Linwen Zhu, and Guodong Xu.
• Department of Cardiothoracic Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China.
• Medicine (Baltimore). 2022 Sep 23; 101 (38): e30543.

AbstractAs a highly conserved endocytic mechanism during evolution, macropinocytosis is enhanced in several malignant tumors, which promotes tumor growth by ingesting extracellular nutrients. Recent research has emphasized the crucial role of macropinocytosis in tumor immunity. In the present study, we established a new macropinocytosis-related algorithm comprising molecular subtypes and a prognostic signature, in which patients with lung adenocarcinoma (LUAD) were classified into different clusters and risk groups based on the expression of 16 macropinocytosis-related long noncoding RNAs. According to the molecular subtypes, we discovered that patients with LUAD in cluster1 had a higher content of stromal cells and immune cells, stronger intensity of immune activities, higher expression of PD1, PDL1, and HAVCR2, and a higher tumor mutational burden, while patients in cluster2 exhibited better survival advantages. Furthermore, the constructed prognostic signature revealed that low-risk patients showed better survival outcomes, earlier tumor stage, higher abundance of stromal cells and immune cells, higher immune activities, higher expression of PD1, PDL1, CTLA4, and HAVCR2, and more sensitivity to Paclitaxel and Erlotinib. By contrast, patients with high scores were more suitable for Gefitinib treatment. In conclusion, the novel algorithm that divided patients with LUAD into different groups according to their clusters and risk groups, which could provide theoretical support for predicting their survival outcomes and selecting drugs for chemotherapy, targeted therapy, and immunotherapy.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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