PSMB7 is associated with anthracycline resistance and is a prognostic biomarker in breast cancer.
BACKGROUND
To date individual markers have failed to correctly predict resistance against anticancer agents in breast cancer. We used gene expression patterns attributable to chemotherapy-resistant cells to detect potential new biomarkers related to anthracycline resistance. One of the genes, PSMB7, was selected for further functional studies and clinical validation.


METHODS
We contrasted the expression profiles of four pairs of different human tumour cell lines and of their counterparts resistant to doxorubicin. Observed overexpression of PSMB7 in resistant cell lines was validated by immunohistochemistry. To examine its function in chemoresistance, we silenced the gene by RNA interference (RNAi) in doxorubicin-resistant MCF-7 breast cancer cells, then cell vitality was measured after doxorubicin treatment. Microarray gene expression from GEO raw microarray samples with available progression-free survival data was downloaded, and expression of PSMB7 was used for grouping samples.


RESULTS
After doxorubicin treatment, 79.8+/-13.3% of resistant cells survived. Silencing of PSMB7 in resistant cells decreased survival to 31.8+/-6.4% (P>0.001). A similar effect was observed after paclitaxel treatment. In 1592 microarray samples, the patients with high PSMB7 expression had a significantly shorter survival than the patients with low expression (P<0.001).


CONCLUSIONS
Our findings suggest that high PSMB7 expression is an unfavourable prognostic marker in breast cancer.
Munkácsy
G
G
Joint Research Laboratory of the Hungarian Academy of Sciences and the Semmelweis University, Semmelweis University 1st Department of Pediatrics, Budapest, Hungary.
Abdul-Ghani
R
R
Mihály
Z
Z
Tegze
B
B
Tchernitsa
O
O
Surowiak
P
P
Schäfer
R
R
Györffy
B
B
D018943:Anthracyclines / Q000378:metabolism* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D005260:Female; D006801:Humans; D011379:Prognosis
D018943:Anthracyclines; D014408:Biomarkers, Tumor; D003546:Cysteine Endopeptidases; C098949:proteasome subunit Z