Abstract
Cancer stem cells (CSCs) represent a subset of tumor cells that are responsible for recurrence and metastasis of tumors. These cells are resistant to radiotherapy and chemotherapy. Immunotherapeutic strategies that target CSCs specifically have provided initial results; however, the mechanism of action of these strategies is unclear. The data were requested from The Cancer Genome Atlas and Genotype-Tissue Expression, followed with the survival analysis and weighted gene co-expression network analysis to detect survival and stemness related genes. Patients were divided into three groups based on their immune status by applying single sample GSEA (ssGSEA) with proven dependability by ESTIMATE analysis. The filtered key genes were analyzed using oncomine, GEPIA, HPA, qRT-PCR, and functional analysis. Patients in a group with a higher stemness and a lower immune infiltration showed a worse overall survival probability, stemness and immune infiltration characteristics of breast cancer progressed in a non-linear fashion. Thirteen key genes related to stemness and immunity were identified and the functional analysis indicated their crucial roles in cell proliferation and immune escape strategies. The qRT-PCR results showed that the expression of PIMREG and MTFR2 differed in different stages of patients. Our study revealed a promising potential for CSC-target immunotherapy in the early stage of cancer and a probable value for PIMREG and MTFR2 as biomarkers and targets for immunotherapy.
Highlights
Breast cancer (BC) has the highest incidence rate and mortality rate among female malignant tumors, which impacts women’s health significantly [1]
This heterogeneity poses are changed during treatment, even through various treatment strategies have been developed based on different pathological types [3], especially for the triple-negative BC [4]
Malta et al as an index for evaluating the stemness of tumor cells, it is considered as a quantitative description of cancer stem cells’ (CSCs)
Summary
Breast cancer (BC) has the highest incidence rate and mortality rate among female malignant tumors, which impacts women’s health significantly [1]. It is considered to be heterogeneous depending on molecular subtype and on different stages of cancer progression [2]. This heterogeneity poses are changed during treatment, even through various treatment strategies have been developed based on different pathological types [3], especially for the triple-negative BC [4]. Growing evidence has established the presence of a subpopulation of cancer cells with stem-like properties in most human malignancies, frequently referred to as ‘cancer stem cells’ (CSCs), which possess the long-term ability to initiate and repopulate tumors [5, 6]. Diverse mechanisms by which CSCs manage to survive through various strategies including tumor initiation, metastatic reactivation, oncogene- and immunetargeted therapy resistance have been unvealed [4, 7]
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