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Figure 1.

Comparison of expression levels of the five LDH isoenzymes.

(A) Schematic depicting the five isomers of LDH, indicating subunit composition. (B) LDH enzymes catalyze the metabolism of pyruvate to lactate to acquire the energy in the glycolytic pathway. (C) Expression levels of the five LDH isoenzymes in the serum of patients with NHL (NHL) and benign (Benign) or healthy controls (HC). **, P<0.01.

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Table 1.

LDH-5 levels and the clinicopathological characteristics of 266 patients with NHL.

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Figure 2.

Comparison of LDH-5 and total LDH levels in NHL patient serum.

(A) ROC analysis of LDH-5 showed that the cutoff value set at 9.1% gives the best diagnostic efficiency (AUC = 0.788, n = 529). (B) The sensitivity and specificity for NHL diagnosis were 53.4% (142/266) and 74.6% (196/263) at the LDH-5 cutoff value (9.1%), respectively. (C) Serum LDH-5 concentration ≥9.1% has more positive results than total LDH ≥250 IU/L in all NHL patients (n = 266) and patients with advanced NHL (III+IV, n = 122). *P<0.05; **P<0.01.

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Figure 3.

Expression patterns of LDH-5 and HIF1α shown by immunohisto-chemical staining in patient tissues.

(A–C) Patients with benign lymphadenectasis, (A) representative examples of HE staining, (B) LDH-5 expression (negative), and (C) HIF1α expression (weak positive); (D–I) Patients with NHL, (D) HE staining; (E) LDH-5 expression in DLBCL (positive), (F) HIF1α expression in DLBCL (positive), and (G) strongly positive expression of LDH-5 in follicular lymphoma; (H) strongly positive expression of LDH-5 in NK/T cell lymphoma; (I) positive expression of LDH-5 in small cell lymphoma. Original magnification, ×400.

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Table 2.

Grading system based on the intensity and extent of LDH5 cytoplasmic and nuclear staining.

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Figure 4.

Immunofluorescence staining for the expression of LDH-5 and HIF1α in malignant NHL and benign lymphadenectasis tissues.

(A) Colocalization of LDH-5 (green) and HIF1α (red) in benign lymphadenectasis (nuclear staining, blue); (B) Colocalization of LDH-5 (green) and HIF1α (red) in malignant NHL (nuclear staining, blue); (C) The correlation of serum LDH-5 and HIF1α expression in peripheral blood of the participants (n = 160) including the patients with NHL (n = 130) and Non-NHL controls (n = 30).

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Figure 5.

Kaplan-Meier progression-free survival curve associated with serum LDH-5 concentrations in 266 NHL patients.

(A) The PFS probability of patients with elevated serum LDH-5 concentrations (>9.1%) was significantly lower than that of patients with normal concentrations (log-rank test, P<0.001); (B) The worse WHO performance status (2–4) was also a significant unfavourable predictor for PFS (P<0.001); (C, D) The PFS was not associated with the gender and histological type of patients (P = 0.199 and P = 0.153, respectively). PFS, progression-free survival.

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Table 3.

Multivariate Cox proportional hazard analyses.

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