Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer.
BACKGROUND
Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC).


METHODS
128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis.


RESULTS
Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17-3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84-2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21-4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample.


CONCLUSIONS
The results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.
Yang
Jun
J
Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Jun.Yang@RoswellPark.org
Ramnath
Nithya
N
Moysich
Kirsten B
KB
Asch
Harold L
HL
Swede
Helen
H
Alrawi
Sadir J
SJ
Huberman
Joel
J
Geradts
Joseph
J
Brooks
John S J
JS
Tan
Dongfeng
D
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D018260:Gelsolin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018260:Gelsolin; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2