Expression and prognostic significance of LIVIN, SURVIVIN and other apoptosis-related genes in the progression of superficial bladder cancer.
BACKGROUND
It has been suggested that progression of superficial bladder cancer may be regulated at the molecular level by a typical pattern of expression of genes involved in apoptosis. Recently LIVIN, belonging to the inhibitors of apoptosis (IAP) family, has been found to be expressed in most solid tumors, where its expression is suggested to have prognostic significance. No data are available concerning the significance of LIVIN in the progression of bladder tumors.


METHODS
In the present paper we used RT-PCR to investigate the expression of LIVIN isoforms alpha and beta, SURVIVIN, BCL-X and BCL-2/BAX expression ratio both in normal and tumoral bladder tissues, and correlated their expression with the emergence of early relapses in a follow-up of 4 years. This study shows that only the alpha isoform of LIVIN, which is not expressed in normal bladder tissue, is expressed in a proportion of tumors with a high risk of relapse.


RESULTS
LIVIN was found in 7/30 patients (23%), SURVIVIN in 9/30 (30%), BCL-2/BAX ratio >1 in 16/30 (53%), BCL-2/BAX expression ratio <1 in 14/30 (46.6%) and BCL-X, only in isoform BCL-X(L), in 11/30 (36.6%). When we evaluated the dependence between each gene expression and relapse free time of patients, we found that LIVIN, high BCL-2/BAX ratio and BCL-X(L), but not SURVIVIN, reached statistical significance in order to predict relapses.


CONCLUSIONS
Our findings suggest that LIVIN may be involved in the progression of superficial bladder cancer and used as a marker of early recurrence; while the expression of SURVIVIN cannot be used to identify patients with high risk of relapse.
Gazzaniga
P
P
Dipartimento di Medicina Sperimentale e Patologia, Università degli Studi di Roma La Sapienza, Rome.
Gradilone
A
A
Giuliani
L
L
Gandini
O
O
Silvestri
I
I
Nofroni
I
I
Saccani
G
G
Frati
L
L
Aglianò
A M
AM
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein