Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer.
BACKGROUND
Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).


METHODS
Immunohistochemical staining was performed on deparaffinized specimens from 82 patients with stage I-IV NSCLC using a polyclonal anti-XOR rabbit antibody. Cytoplasmic XOR staining was scored on frequency and intensity scales from 0 to 4 with low expression defined as 0-1 and high expression defined as ≥2-4. XOR immunostaining was correlated with clinical characteristics and outcomes and analyzed using Kaplan-Meier and Cox proportional hazard methods.


RESULTS
Positive XOR expression was observed in 53/82 cases (65%). Patients with high XOR frequency had a longer median survival of 3053 days (95% CI: 2190-3916) vs. 592 days (95% CI: 492-692 days) for patients with low XOR frequency, p=0.0089, HR 0.47. Neither XOR intensity nor the overall score of XOR frequency multiplied by XOR intensity demonstrated any significant association with survival. Surgical resection was performed on 61 patients of which 34 (56%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy with low XOR expression, 15/34 (44%) had a shortened median survival compared with patients who received adjuvant chemotherapy with high XOR expression (543 days vs. 2023 days, respectively, p=0.007 and HR=0.33).


CONCLUSIONS
Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with NSCLC who received adjuvant chemotherapy. Further studies of the XOR pathway are warranted to validate and mechanistically explain these outcomes.
Kim
Anthony W
AW
Section of Thoracic Surgery, Yale University School of Medicine, New Haven, CT 06520, United States. anthony.kim@yale.edu
Batus
Marta
M
Myint
Ronald
R
Fidler
Mary J
MJ
Basu
Sanjib
S
Bonomi
Philip
P
Faber
L Penfield
LP
Wightman
Sean C
SC
Warren
William H
WH
McIntire
Maria
M
Arvanitis
Leonidas D
LD
Gattuso
Paolo
P
Xu
Xiulong
X
Liptay
Michael J
MJ
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome; D014968:Xanthine Dehydrogenase / Q000378:metabolism*
D014968:Xanthine Dehydrogenase