Comprehensive Characterization of Tumor Purity and Its Clinical Implications in Gastric Cancer

Abstract

Solid tumour tissues are composed of tumour and non-tumour cells, such as stromal cells and immune cells. These non-tumour cells constitute an essential part of the tumour microenvironment (TME), which decrease the tumour purity and play an important role in carcinogenesis, malignancy progression, treatment resistance and prognostic assessment. However, the implications of various purity levels in gastric cancer (GC) remain largely unknown. In the present study, we used an in-silico approach to infer the tumour purity of 2,259 GC samples obtained from our hospital and 12 public datasets based on the transcriptomic data. We systematically evaluated the association of tumour purity with clinical outcomes, biological features, TME characteristics and treatment response in GC. We found that tumour purity might be a patient-specific intrinsic characteristic of GC. Low tumour purity was independently correlated with shorter survival time and faster recurrence and significantly associated with mesenchymal, invasive and metastatic phenotypes. Integrating GC purity into a clinical prognostic nomogram significantly improved predictive validity and reliability. In addition, low tumour purity was strongly associated with immune and stromal cell functions. Fibroblasts, endothelial cells and monocytes were markedly enriched in low-purity tumours, serving as robust indicators of a poor prognosis. Moreover, patients with low GC purity may not benefit more from adjuvant chemotherapy. Our findings highlight that tumour purity confers important clinical, biological, microenvironmental and treatment implications for patients with GC. Therefore, a comprehensive evaluation of tumour purity in individual tumours can provide more insights into the molecular mechanisms of GC, facilitate precise classification and clinical prediction and help to develop more effective individualised treatment strategies.

Epigenetically regulated gene expression profiles decipher four molecular subtypes with prognostic and therapeutic implications in gastric cancer

“…Notably, our findings indicated that patients of C1 subtype typically exhibit higher tumor purity. As previous reports, a higher tumor purity generally reveals a better prognosis in GC and more likely to benefit from adjuvant chemotherapy [ 43 , 44 ], which not only validated the better survival of C1 subtype but also suggested that C1 patients might benefit more from neoadjuvant chemotherapy.…”

A Novel Risk Model Based on Autophagy-Related LncRNAs Predicts Prognosis and Indicates Immune Infiltration Landscape of Patients With Cutaneous Melanoma

“…Notably, we found that the tumor purity of CM patients with high-risk scores was higher than that of patients with low-risk scores, suggesting a higher proportion of tumor cells in the tumor tissue. Generally, a high tumor purity implies a shorter survival probability and is more likely to be diagnosed as malignant (Lou et al, 2021). In this study, we found that better overall survival was correlated with lower tumor purity and higher immune score, indicating that patients with high-risk scores have worse survival status.…”

Identification and Validation of METTL3-Related Molecules for Predicting Prognosis and Efficacy of Immunotherapy in Gastric Cancer Based on m6A Methylome and Transcriptome Sequencing Analysis

“…The low infiltration of CD8 T cells and the high infiltration of memory-activated CD4 T cells in type B GC cancer may increase the efficacy of immune checkpoint inhibitor therapy in GC patients. Decreased tumor purity also plays a vital role in the malignant progression of GC, treatment resistance, and prognostic assessment (38). These differences in the infiltration of immune cells may be related to the differences in the prognosis and clinical pathological stages of the patients with different subtypes.…”