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Int J Biol Sci 2023; 19(7):2256-2269. doi:10.7150/ijbs.74653 This issue Cite

Research Paper

Exploration of spatial heterogeneity of tumor microenvironment in nasopharyngeal carcinoma via transcriptional digital spatial profiling

Liping Wang^1#, Dujuan Wang^2#, Xiaojiao Zeng¹, Qian Zhang¹, Huiqing Wu³, Jie Liu⁴, Yang Wang^4✉, Guohong Liu^3✉, Yunbao Pan^1✉

1. Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
2. Department of Clinical Pathology, Houjie Hospital of Dongguan, The Affiliated Houjie Hospital of Guangdong Medical University, Dongguan, China.
3. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
4. State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
^#Equally contribution and co-first authors.

✉ Corresponding authors: Yunbao Pan, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China; E-mail: panyunbaocom. Guohong Liu, Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China; E-mail: liuguohcom; Yang Wang, State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, No.368 Street, Wuchang District, Wuhan 460032, China; E-mail: yangwangedu.cn. More

Abstract

The heterogeneity of nasopharyngeal carcinoma (NPC) leads to mixed clinical outcomes. We collected 92 regions of interest from 41 biopsies of patients with untreated NPC and obtained their transcripts using GeoMx Digital Spatial Profiling (DSP) technology. Spatial heterogeneity was determined by measuring the expression of marker genes in tumor cell-enriched (PanCK-expressing), immune cell-enriched (CD45-expressing), and normal epithelial (Endo) regions. We screened 16 prognostic markers in tumor cell-enriched regions and 4 prognostic markers in immune cell-enriched regions. The levels of CD8⁺ T follicular helper T cells, activated NK cells, and M0 macrophage contents were higher in tumor cell-enriched regions than in immune cell-enriched regions. Conversely, plasma cell and M2 macrophage levels were lower. The follicular helper T cells in tumor cell-enriched regions were negatively correlated with resting NK cells and positively correlated with activated NK cells. In immune cell-enriched regions, this relationship was reversed. We also explored the heterogeneity of HLA gene families, immune checkpoints, and metabolism-related genes in the three regions. In tumor cell-enriched regions, we obtained 19 prognosis-related metabolism genes via univariate cox analysis. We used multiplex immunofluorescence to verify the elevated expression of SLC8A1 and MDH1 in immune cell-enriched regions and tumor cell-enriched regions, respectively, both of which were associated with prognosis of NPC. In conclusion, we explored the spatial heterogeneity of the NPC tumor environment and found specific diagnostic and prognostic markers that can be used to differentiate tumor cell-enriched regions from immune cell-enriched regions in NPC.

Keywords: Nasopharyngeal carcinoma, Tumor microenvironment, Immune infiltration, Metabolic marker, Immune checkpoints, Digital spatial profiling

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