Abstract 3335: Non-tumor-bearing tissue: A prognostic biomarker for cancer

Abstract Background: We hypothesized that distinct microenvironments either support or inhibit the growth of cancer cells, and that the non-tumor bearing tissue (NBT) reflects these microenvironments. Additionally, we assumed that the more closely the characteristics of the NBT resemble those of the tumor, the greater the likelihood of supporting cancer cell progression and promoting disease recurrence. Method: We investigated TCGA dataset with more than 20 samples of NBT and paired tumors. We employed a scoring system using the top 10-50 DEGs with high fold-change values in tumors. We scored the expression of the tumor-supportive signature genes in the NBT using single-sample gene set enrichment analysis (ssGSEA). We evaluated the mean score derived from the top 10-50 in the NBT to categorize the patients into two groups that most effectively facilitated prognostic differentiation. The groups were defined as follows: patients showing relatively high tumor supportive signatures in NBT (patients with tumor-supportive microenvironment in NBT; TSM), and patients showing relatively low supportive signatures in NBT (patients with healthy microenvironment in NBT; HM). Results: Among the 12 cancers, the significantly poorer overall survival (OS) in TSM were identified in head and neck cancer squamous cell carcinoma (HNSC; hazard ratio [HR]: 2.06 [1.03 - 4.10]), lung squamous cell carcinoma (LUSC; hazard ratio [HR]: 3.87 [1.69 - 8.90]), kidney renal cell carcinoma (KIRC; hazard ratio [HR]: 2.85 [1.31 - 6.21]). In other cancer types, there are no prognostic differentiations. The 3-year overall survival in the TSM group compared to the HM group were markedly lower: HNSC (0.569 vs. 0.813), LUSC (0.242 vs. 0.492), and KIRC (0.250 vs. 0.689). Pathway analysis suggested that leukocyte-mediated immunity and inflammatory pathways were upregulated, whereas the maintenance of epithelial barriers was decreased in the NBT of the TSM group in HNSC, LUSC and KIRC. Immune cell deconvolution analysis revealed that the TSM group had a significantly higher proportion of neutrophils compared to that of the HM group in HNSC and LUSC. In KIRC, significantly higher proportion of CD8+ T cells and memory CD4+ T cells were observed in the NBT of the TSM group. Conclusions: Our findings suggest that NBT serves as a prognostic biomarker that effectively predicts cancer invasiveness and tumor-promoting inflammation, particularly in HNSC, LUSC, and KIRC. This also highlights the importance of maintaining a healthy microenvironment. Citation Format: Ji Hye Choi Yeong Hak Bang YeonJu Lee Woong-Yang Park. Non-tumor-bearing tissue: A prognostic biomarker for cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3335.