Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias.
Survivin has been identified as one of the top 4 transcripts among 3.5 million human transcriptomes uniformly up-regulated in cancer tissues but not in normal tissues. Therefore, we quantitatively determined the messenger RNA (mRNA) expression profile for survivin by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 113 patients with leukemias, such as adult T-cell leukemia (ATL), acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia in crisis, and chronic lymphocytic leukemia (CLL), and in 25 cell lines, including 7 ATL cell lines and 15 solid-tumor cell lines. Furthermore, we examined whether the plasma level of survivin protein as measured by enzyme-linked immunosorbent assay (ELISA) substituted for mRNA expression by PCR quantification. Gene expression was quantitatively confirmed to be up-regulated in approximately 90% of ATL and acute leukemia cases and in all of the cell lines tested, whereas it was down-regulated in almost all cases of CLL. Furthermore, with respect to the interpretation of the gene expression findings, attention was paid to standardization with a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the real-time PCR quantification, because the variability in GAPDH expression among the different cell types was significant. GAPDH expression was relatively low in ATL cells and high in ALL and AML cells. The rates of increase in the levels of survivin protein in the plasma of ATL patients and in the supernatants from in vitro cultures of solid-tumor cell lines were low compared with rates of increase of the mRNA and protein level in the cells, suggesting that the protein levels in plasma do not always reflect survivin expression in tumor cells. Our findings indicate the potential clinical relevance of survivin quantified by real-time PCR but not for the protein level in plasma as determined by ELISA, especially in cases of ATL and acute leukemias.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kazuyuki
K
Sugahara
Akiko
A
Uemura
Hitomi
H
Harasawa
Hiroshi
H
Nagai
Yoichi
Y
Hirakata
Masao
M
Tomonaga
Kenn
K
Murata
Hiroshi
H
Sohda
Toru
T
Nakagoe
Sin-ichi
S
Shibasaki
Yasuaki
Y
Yamada
Shimeru
S
Kamihira
D000208:Acute Disease; D000328:Adult; D014408:Biomarkers, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D007945:Leukemia, Lymphoid / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D007951:Leukemia, Myeloid / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000097:blood / Q000235:genetics*; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin