Integrating ANP32A expression with Ann Arbor stage refines prognostic stratification in extranodal NK/T-cell lymphoma

To investigate the expression of acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A) in extranodal NK/T-cell lymphoma (ENKTL) and to evaluate its relationship with clinicopathological characteristics, proliferative activity, and prognosis.

A total of 63 patients with ENKTL diagnosed at the First Affiliated Hospital of Zhengzhou University between 2012 and 2021 were retrospectively included. Reactive lymphoid tissue from the nasopharynx was used as the control tissue. Immunohistochemistry was performed to detect ANP32A expression in ENKTL and control tissues. The association between ANP32A expression and clinicopathological characteristics, Ki-67 index, and patient survival was analyzed. Kaplan-Meier survival analysis, univariate and multivariate Cox regression analyses, and receiver operating characteristic (ROC) curve analysis were performed to assess the prognostic significance of ANP32A.

Among the 63 patients with ENKTL, there were 42 males and 21 females, with a median age of 50 years (range, 12-80 years). Compared with control tissues, ANP32A expression was increased in ENKTL tissues, and positive staining was mainly localized in the nuclei of tumor cells. According to the modified H-score, 23 cases showed high ANP32A expression and 40 cases showed low expression. High ANP32A expression was significantly associated with advanced Ann Arbor stage, higher Prognostic Index for Natural Killer Lymphoma (PINK) score, elevated β2-microglobulin level, and high Ki-67 index (all P < 0.05). Spearman correlation analysis showed a weak positive correlation between ANP32A expression and Ki-67 index (r = 0.330, P < 0.01). Kaplan-Meier analysis showed that patients with high ANP32A expression had significantly shorter overall survival (OS) than those with low expression (log-rank P < 0.0001). Univariate Cox regression analysis showed that high ANP32A expression was associated with poor prognosis (hazard ratio(HR) = 4.55; 95% confidence interval (CI), 2.50-8.52; P < 0.001). Multivariate Cox regression analysis further demonstrated that ANP32A high expression remained an independent adverse prognostic factor (HR = 3.61, 95% CI: 1.95-6.89, P < 0.001). ROC analysis showed that the area under the curve (AUC) of ANP32A alone for predicting OS was 0.776, which was higher than that of Ann Arbor stage alone (AUC = 0.667); when combined with Ann Arbor stage, the AUC increased to 0.800.

ANP32A is increased in ENKTL and is associated with aggressive clinicopathological features, increased proliferative activity, and poor survival outcome. ANP32A may serve as a useful supplementary prognostic marker in ENKTL and may provide additional prognostic information when combined with Ann Arbor stage.