Identifying 8-mRNAsi Based Signature for Predicting Survival in Patients With Head and Neck Squamous Cell Carcinoma via Machine Learning
FRONTIERS IN GENETICS
Authors: Tian, Yuxi; Wang, Juncheng; Qin, Chao; Zhu, Gangcai; Chen, Xuan; Chen, Zhixiang; Qin, Yuexiang; Wei, Ming; Li, Zhexuan; Zhang, Xin; Lv, Yunxia; Cai, Gengming
Abstract
Cancer stem cells (CSCs) have been characterized by several exclusive features that include differentiation, self-renew, and homeostatic control, which allows tumor maintenance and spread. Recurrence and therapeutic resistance of head and neck squamous cell carcinomas (HNSCC) have been identified to be attributed to CSCs. However, the biomarkers led to the development of HNSCC stem cells remain less defined. In this study, we quantified cancer stemness by mRNA expression-based stemness index (mRNAsi), and found that mRNAsi indices were higher in HNSCC tissues than that in normal tissue. A significantly higher mRNAsi was observed in HPV positive patients than HPV negative patients, as well as in male patients than in female patients. The 8-mRNAsi signature was identified from the genes in two modules which were mostly related to mRNAsi screened by weighted gene co-expression network analysis. In this prognostic signatures, high expression of RGS16, LYVE1, hnRNPC, ANP32A, and AIMP1 focus in promoting cell proliferation and tumor progression. While ZNF66, PIK3R3, and MAP2K7 are associated with a low risk of death. The riskscore of eight signatures have a powerful capacity for 1-, 3-, 5-year of overall survival prediction (5-year AUC 0.77, 95% CI 0.69-0.85). These findings based on stemness indices may provide a novel understanding of target therapy for suppressing HNSCC stem cells.
The effect of neoadjuvant chemotherapy on the correlation of tumor-associated macrophages with CD31 and LYVE-1
IMMUNOBIOLOGY
Authors: Mitrofanova, Irina; Zavyalova, Marina; Riabov, Vladimir; Cherdyntseva, Nadezhda; Kzhyshkowska, Julia
Abstract
Angiogenesis and lymphangiogenesis play a crucial role in tumor growth, invasion and metastasis. Tumor-associated macrophages (TAM) induce both angiogenesis and lymphangiogenesis in mouse breast cancer models and positively correlate with these processes in human breast cancer patients. Neoadjuvant chemotherapy (NAC) is a widely used therapeutic option for cancer treatment. However, the effect of NAC on the distribution of TAM within intratumoral compartments and their correlation with angiogenesis and lymphangiogenesis remained unknown. In the present study we analyzed the effect of NAC on the distribution of CD68+ and stabilin-1 + TAM in five functionally distinct areas of human breast cancer and their correlations with microvessel density (MVD) and lymphatic microvessel density (LMVD), identified by CD31 and LYVE1, respectively. We found that NAC enhances blood vessel density in soft fibrous stroma and in coarse fibrous stroma. Without NAC the amount of CD68+ TAM in gaps of ductal tumor structures positively correlate with CD31 + microvessel density in soft fibrous stroma. NAC had enhancing effect on the amount of CD68 + TAM but not stabilin-1 + TAM in soft fibrous stroma. However, no correlation between TAM and CD31 + microvessel density was identified after NAC. NAC did not enhance the lymphatic microvessel density. But after NAC stabilin-1 expressing subpopulation of TAM positively correlated with expression of LYVE-1. We hypothesized that CD68+ TAM can support tumor angiogenesis primarily before NAC, while stabilin-1 + TAM can contribute to the maintenance of lymphatic microvessel density after NAC.