Nuclear localization of apoptosis protease activating factor-1 predicts survival after tumor resection in early-stage non-small cell lung cancer.
The proapoptotic protein apoptosis protein activating factor-1 (Apaf-1), which is normally located in the cytoplasm, can translocate to the nucleus before non-small cell lung carcinoma (NSCLC) cells manifest signs of apoptosis such as mitochondrial damage, caspase activation, or chromatin condensation. This may indicate a stage of imminent apoptosis. Importantly, we found that 24% (15 of 62) of resected stage I NSCLC (T(1)N(0)M(0) or T(2)N(0)M(0)), manifested a marked nuclear localization of Apaf-1 (Apaf-1(Nuc)), as compared with the mostly cytoplasmic localization of Apaf-1 found in the remaining tumors (Apaf-1(Cyt)). After a median follow-up of 6.31 years, the actuarial 5-year overall survival rates were 89% (56-98%) in the Apaf-1(Nuc) group and 54% (36-71%) in the Apaf-1(Cyt) group (P = 0.039). No correlation between the subcellular localization of Apaf-1 and that of p53 and Hsp70 could be established. Thus, the subcellular location of Apaf-1 (but not that of p53 or Hsp70) constitutes an accurate prognostic factor for overall survival in NSCLC.
Besse
Benjamin
B
Institut Gustave Roussy, Division of Cancer Medicine, Villejuif, France.
Candé
Céline
C
Spano
Jean-Philippe
JP
Martin
Antoine
A
Khayat
David
D
Le Chevalier
Thierry
T
Tursz
Thomas
T
Sabatier
Laure
L
Soria
Jean-Charles
JC
Kroemer
Guido
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053477:Apoptotic Protease-Activating Factor 1; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology*; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D013347:Subcellular Fractions; D015996:Survival Rate
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D002843:Chromatin; D011506:Proteins; D020169:Caspases