Chemoresponse to docetaxel correlates with expression of the survivin splicing variants in patients with gastric cancer.
OBJECTIVE
Survivin, a potential predictive marker to chemotherapeutic drugs, reduces the susceptibility of tumor cells to proapoptotic stimuli, thereby promoting tumor cell survival during tumor treatment with anticancer agents. In the present study, we examined the correlation between drug-response and expression of survivin in gastric cancer.


METHODS
Drug-response was performed by histoculture drug-response assay (HDRA) in 42 patients with advanced gastric cancer. Survivin variants was studied by real-time RT-PCR at mRNA levels.


RESULTS
In our data, twenty-one cases (50%) were sensitive to at least one of drugs tested in the HDRA and 80% (16/20) were positively confirmed clinically, with 100% sensitivity and 83.3% specificity. The diagnostic efficacy of the HDRA were calculated as the area under the receiver operating characteristic (AUC-ROC) curve and showed a value of 0.917. More importantly, significant statistical differences (p=0.012) in chemoresponse to docetaxel were revealed depending on the mRNA level of wild-type survivin.


CONCLUSIONS
These clinical data demonstrated, for the first time, that wild-type survivin is useful for evaluating the docetaxel-response in patients with gastric cancer. Moreover, the HDRA is an excellent clinical useful drug-response assay for patients to individualize their chemotherapy.
Meng
Hua
H
Department of Surgery, Beijing Cancer Hospital, Peking University School of Oncology, Beijing, China.
Tanigawa
Nobuhiko
N
Hao
Chun-Yi
CY
Dai
De-Jian
DJ
Lu
Cai-De
CD
Ji
Jia-Fu
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D014644:Genetic Variation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019154:Protein Splicing; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000077022:Survivin; D043823:Taxoids / Q000627:therapeutic use*
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D054316:Biomarkers, Pharmacological; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel