Snx20, a member of the sorting nexin family of proteins, plays a crucial role in the regulation of innate immunity [1]. It is involved in the endo-lysosomal network and may function as an endosome-associated scaffold due to the presence of a PX-associated B (PXB) domain [5,6]. The PX domain of Snx20 acts as a phosphoinositide recognition module, targeting it to specific endocytic membrane domains [6].

In lung adenocarcinoma (LUAD), Snx20 is downregulated in most cases, and its low expression is associated with poor prognosis and can be an independent prognostic factor. Biofunctional analysis shows that genes co-expressed with Snx20 mainly promote the immune process and inhibit cell proliferation in LUAD. High Snx20 expression is accompanied by a better immune microenvironment and survival, and it is significantly associated with various tumor-infiltrating immune cells, affecting immune infiltration in the tumor microenvironment [1,4]. In low-grade glioma (LGG), Snx20 is up-regulated, and its higher expression is related to adverse clinical outcomes. DNA hypomethylation leads to its overexpression in LGG, and it is mainly involved in immune response and inflammatory response-related signaling pathways. Also, its increased expression is correlated with infiltration levels of various immune cells and immune checkpoint in LGG [2]. In lung adenocarcinoma patients treated with PD-1 inhibitors, Snx20 expression can predict the clinical response, and high Snx20/high PD-L1 expression group has longer overall survival [3].

In conclusion, Snx20 is significantly associated with immune cell infiltration and prognosis in multiple cancers, such as LUAD and LGG. Its role in regulating the immune microenvironment and response to immunotherapy suggests its potential as an immune-related biomarker and therapeutic target in these cancer types.

References:

1. Wu, Gu Jie, Ren, Kuan, He, Min, Bo, Ding, Xue, Qun. 2021. SNX20 Expression Correlates with Immune Cell Infiltration and Can Predict Prognosis in Lung Adenocarcinoma. In International journal of general medicine, 14, 7599-7611. doi:10.2147/IJGM.S337198. https://pubmed.ncbi.nlm.nih.gov/34764676/

2. Chen, Xi, Jiang, Xiulin, Wang, Heping, Pu, Jun, Li, Chen. 2022. DNA methylation-regulated SNX20 overexpression correlates with poor prognosis, immune cell infiltration, and low-grade glioma progression. In Aging, 14, 5211-5222. doi:10.18632/aging.204144. https://pubmed.ncbi.nlm.nih.gov/35771139/

3. Fan, Linwei, Li, Li, Huang, Chunye, Deng, Jun, Xiong, Jianping. 2020. Increased SNX20 and PD-L1 Levels Can Predict the Clinical Response to PD-1 Inhibitors in Lung Adenocarcinoma. In OncoTargets and therapy, 13, 10075-10085. doi:10.2147/OTT.S262909. https://pubmed.ncbi.nlm.nih.gov/33116590/

4. Yuan, Yixiao, Jiang, Xiulin, Tang, Lin, Zou, Xiaolan, Duan, Lincan. 2021. SNX20AR/MiRNA-301a-3p/SNX20 Axis Associated With Cell Proliferation and Immune Infiltration in Lung Adenocarcinoma. In Frontiers in molecular biosciences, 8, 744363. doi:10.3389/fmolb.2021.744363. https://pubmed.ncbi.nlm.nih.gov/34604311/

5. Danson, Chris M, Pearson, Neil, Heesom, Kate J, Cullen, Peter J. 2018. Sorting nexin-21 is a scaffold for the endosomal recruitment of huntingtin. In Journal of cell science, 131, . doi:10.1242/jcs.211672. https://pubmed.ncbi.nlm.nih.gov/30072438/

6. Clairfeuille, Thomas, Norwood, Suzanne J, Qi, Xiaying, Teasdale, Rohan D, Collins, Brett M. 2015. Structure and Membrane Binding Properties of the Endosomal Tetratricopeptide Repeat (TPR) Domain-containing Sorting Nexins SNX20 and SNX21. In The Journal of biological chemistry, 290, 14504-17. doi:10.1074/jbc.M115.650598. https://pubmed.ncbi.nlm.nih.gov/25882846/