Objective To investigate the expression of ubiquitin-specific peptidase 15 (USP15) in cancerous and adjacent non-cancerous tissues of patients with non-small cell lung cancer (NSCLC) and its relationships with clinicopathological features and prognosis.

Methods Cancerous tissue samples and paired adjacent non-cancerous tissue samples were collected from 137 NSCLC patients who underwent surgical treatment. Reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting (WB), and immunohistochemistry (IHC) were used to detect the expression of USP15 in cancerous and adjacent non-cancerous tissues. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare survival differences among patients with different USP15 protein expression levels. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of USP15 for the prognosis of NSCLC patients. Univariate and multivariate Cox regression analyses were conducted to screen the factors influencing the prognosis of NSCLC patients.

Results The results of RT-qPCR and WB showed that compared with adjacent non-cancerous tissues, the expression levels of USP15 mRNA and USP15 protein in lung adenocarcinoma and lung squamous cell carcinoma tissues were increased, with statistically significant differences (P < 0.05). The results of IHC showed that the high expression rate of USP15 in cancerous tissues of NSCLC patients was higher than that in adjacent non-cancerous tissues, with a statistically significant difference (P < 0.05). The expression levels of USP15 in cancerous tissues of NSCLC patients with a maximum tumor diameter≥3 cm, lymph node metastasis, TNM stage Ⅲ to Ⅳ, and low differentiation were respectively higher than those in patients with a maximum tumor diameter < 3 cm, no lymph node metastasis, TNM stage Ⅰ to Ⅱ, and moderate-to-high differentiation, with statistically significant differences (P < 0.05). Kaplan-Meier survival curve analysis showed that during a 3-year follow-up, the median survival time of patients with high USP15 expression was 12.2 months, which was shorter than the 30.4 months of patients with low USP15 expression, with a statistically significant difference (Log-rank χ²=7.664, P=0.006). During a 5-year follow-up, the median survival time of patients with high USP15 expression was 27.4 months, which was shorter than the 50.6 months of the low USP15 expression group, with a statistically significant difference (Log-rank χ²=54.359, P < 0.001). ROC curve analysis showed that the area under the curve for USP15 in predicting the prognosis of NSCLC patients was 0.955. Multivariate Cox regression analysis showed that lymph node metastasis, low differentiation, TNM stage Ⅲ-Ⅳ, and high USP15 expression were independent risk factors for poor prognosis in NSCLC patients during a 3-year follow-up (P < 0.05).

Conclusion USP15 is upregulated in cancerous tissues of NSCLC patients, and its expression is related to lymph node metastasis, TNM stage, and differentiation. High USP15 expression is an independent risk factor for poor prognosis in NSCLC patients.