Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.
S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.
Lower Silesian Centre of Oncology, Wrocław, Poland.
Adam
A
Maciejczyk
Aleksandra
A
Łacko
Marcin
M
Ekiert
Ewa
E
Jagoda
Teresa
T
Wysocka
Rafał
R
Matkowski
Agnieszka
A
Hałoń
Balázs
B
Györffy
Hermann
H
Lage
Paweł
P
Surowiak
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C103003:S100P protein, human