Cancer Stem Cell-Related Gene Periostin: A Novel Prognostic Marker for Breast Cancer

Abstract

We investigated the expression status of periostin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer. CD44+/CD24−/line- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. Periostin expression status was detected in CSC cells and 1,086 breast cancer specimens by Western blot and immunohistochemistry staining, with the CSC ratio determined by immunofluorescence double staining. The relationship between the periostin protein and clinico-pathological parameters and prognosis was subsequently determined. As a result, CSC cells are more likely to generate new tumors in mice and cell microspheres that are deficient in NOD/SCID compared to the control group. Periostin protein was expressed higher in CSC cells compared to the control cells and was found to be related to CSC chemotherapy resistance. Moreover, periostin expression was found to be related to the CSC ratio in 1,086 breast cancer specimens (P = 0.001). In total, 334 (30.76%) of the 1,086 breast cases showed high periostin expression. After universal and Spearman regression correlation analysis, periostin was observed to be related to histological grade, CSC ratio, lymph node metastasis, tumor size, and triple-negative breast cancer (all P<0.05). Furthermore, periostin was shown to attain a significantly more distant bone metastasis and worse disease-specific survival than those with none or low-expressed periostin protein (P = 0.001). In the Cox regression test, periostin protein was detected as an independent prognostic factor (P = 0.001). In conclusion, periostin was found to be related to the CSC and an independent prognostic factor for breast cancer. It is also perhaps a potential target to breast cancer.

The role of periostin in neoplastic processes

“…In more recent study, Xu et al [57] Higher expression of POSTN mRNA and protein levels in ovarian tumors compared to normal/benign tumor samples…”

“…In addition, multivariate analysis demonstrated that high POSTN expression may be an independent prognostic factor in breast cancer [57].…”

“…The 5-year survival rate was better in patients with negative POSTN expression than in those with positive POSTN expression. POSTN expression in cancer stroma may have prognostic relevance in ovarian cancer [78] In [57]. The immunohistochemical staining revealed that the expression of POSTN mainly occurred in the cytoplasm and plasma membrane of the breast cancer cells.…”

“…Increased expression of POSTN has been observed in various tumor types, including breast [44,48,[56][57][58], NSCLC [27,49,[59][60][61][62], colorectal [19,29,63], stomach cancers [64][65][66][67][68], pancreatic [32,69], prostate [70][71][72][73][74][75], ovarian cancer [76][77][78][79], and glioblastomas [80][81][82] (Table 1).…”

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy

“…A previous study demonstrated that POSTN protein expression was increased in CD44 + /CD24 -breast cancer stem cells compared with control cells, which was associated with cancer stem cell chemotherapy resistance (10). In the serum of patients with early-stage breast cancer, POSTN expression could be detected prior to surgery, and increased baseline serum POSTN levels were predictive of worse long-term survival outcomes in specific subgroups of patients (11).…”