Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis

Luo TANG; Li FAN; Liu CAO

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Luo TANG, Li FAN, Liu CAO. Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis[J]. Journal of Kunming Medical University.

Citation:

Luo TANG, Li FAN, Liu CAO. Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis[J]. Journal of Kunming Medical University.

Luo TANG, Li FAN, Liu CAO. Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis[J]. Journal of Kunming Medical University.

Citation:

Luo TANG, Li FAN, Liu CAO. Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis[J]. Journal of Kunming Medical University.

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Expression of USP8，USP15，and USP21 in Nasopharyngeal Carcinoma Tissues and Their Association with Prognosis

Department of Otolaryngology，Sichuan Hospital of Integrated Traditional Chinese and Western Medicine，Chengdu Sichuan 610041，China

Received Date: 2026-03-03
Available Online: 2026-10-29

Abstract

Abstract

Objective To investigate the expression of ubiquitin-specific protease 8 （USP8）, USP15, and USP21 in nasopharyngeal carcinoma （NPC） tissues and their relationship with prognosis. Methods A total of 227 patients with NPC who received treatment at Sichuan Provincial Hospital of Integrated Traditional Chinese and Western Medicine from March 2019 to March 2022 were retrospectively selected as the study subjects, and paired NPC tissues and adjacent non-tumor tissues were collected from all patients. Based on immunohistochemistry （IHC） scores, the patients were divided into a USP8 high-expression group （n = 159） and a low-expression group （n = 68）, a USP15 high-expression group （n = 168） and a low-expression group （n = 59）, and a USP21 high-expression group （n = 174） and a low-expression group （n = 53）. According to the 3-year follow-up outcomes, the patients were divided into a survival group （n = 102） and a death group （n = 125）. Expression levels of USP8, USP15, and USP21 in nasopharyngeal carcinoma （NPC） tissues and adjacent non-tumor tissues were detected using reverse transcription quantitative real-time polymerase chain reaction （RT-qPCR）, Western blotting （WB）, and immunohistochemistry （IHC）; the expression of USP8, USP15, and USP21 in NPC patients with different pathological characteristics was compared; the relevant factors affecting the prognosis of NPC patients were analyzed by unifactorial and multifactorial Cox regression; and the Kaplan-Meier curve method and log-rank test were used to analyze the relationship between the expression of USP8, USP15, USP21 and the prognosis of NPC patients. The predictive efficacy of USP8, USP15, and USP21 for poor prognosis in NPC patients was evaluated using receiver operating characteristic （ROC） curve analysis. Results Compared with paired adjacent non-tumor tissues, mRNA and protein expression levels, as well as the proportion of high expression, of USP8, USP15, and USP21 were significantly elevated in NPC tissues （P < 0.05）. Compared with patients without lymph node metastasis, with lesions located in the pharyngeal recess （vs. superior/lateral wall）, with clinical stage III–IV （vs. stage I–II）, without tumor residue, with tumor T3–T4 classification （vs. T1-T2）, with moderately/well-differentiated tumors （vs. moderate/well-differentiated）, and without distant metastasis, the proportions of high expression of USP8, USP15, and USP21 were significantly increased in patients with lymph node metastasis, with lesions located in the pharyngeal recess, with clinical stage III–IV, with tumor residue, with tumor T3–T4 stage, with poorly differentiated tumors, and with distant metastasis （all P < 0.05）. Multifactorial Cox regression analysis showed that lesion site （pharyngeal crypt）, clinical stage III-IV, poor differentiation, distant metastasis, high expression of USP8, high expression of USP15, and high expression of USP21 were all independent risk factors for poor prognosis of patients with NPC （P < 0.05）.The results of the Kaplan-Meier survival curves showed that the differences between the high-expression and low-expression groups of USP8, USP15, USP21 were statistically significant （log-rank χ² = 10.097, 12.429, 6.122, P < 0.001）. ROC curve analysis showed that the combined AUC of USP8, USP15, and USP21 for predicting poor prognosis in NPC patients was 0.987, which was significantly higher than that of USP8 alone （Z = 2.492, P = 0.012）, USP15 alone （Z = 5.734, P < 0.001）, or USP21 alone （Z = 6.115, P < 0.001）. Conclusion USP8, USP15, and USP21 were significantly upregulated in NPC tissues; their high expression was associated with adverse clinicopathological features, and all three were independent risk factors for poor prognosis in NPC patients. The combined detection of the three showed high predictive value for poor prognosis in NPC, suggesting that they may serve as a novel biomarker combination for predicting disease progression and poor prognosis in NPC.
- Nasopharyngeal carcinoma,
- USP8,
- USP15,
- USP21,
- Prognosis

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