Expression of phosphorylated p21-activated kinase 4 is associated with aggressive histologic characteristics and poor prognosis in patients with surgically treated renal cell carcinoma
| Autor: | Ho Won Kang, Xuan-Mei Piao, Hee Youn Lee, Kyeong Kim, Sung Pil Seo, Yun-Sok Ha, Yeong Uk Kim, Won Tae Kim, Yong-June Kim, Sang-Cheol Lee, Wun-Jae Kim, Eun-Young Shin, Eung-Gook Kim, Seok Joong Yun |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Investigative and Clinical Urology, Vol 62, Iss 4, Pp 399-407 (2021) |
| Druh dokumentu: | article |
| ISSN: | 2466-0493 2466-054X |
| DOI: | 10.4111/icu.20200399 |
| Popis: | Purpose: P21-activated kinase 4 (PAK4), a serine/threonine kinase that regulates a number of fundamental cellular processes, has been suggested as a prognostic factor for various human tumors. The aim of the present study was to evaluate the clinical implications of phospho-Ser474 PAK4 (pPAK4S474), an activated form of PAK4, in surgically treated renal cell carcinoma (RCC). Materials and Methods: Samples from 131 patients with surgically treated RCC were immunostained to detect PAK4 and pPAK4S474. Expression of PAK4 and pPAK4S474 was compared with clinicopathological characteristics and survival after nephrectomy. Results: PAK4 and pPAK4S474 were expressed predominantly in the nucleus. Overall, 57.3% (75/131) and 24.4% (29/119) of specimens exhibited high expression of pPAK4S474 and PAK4, respectively. High expression of pPAK4S474 was associated with adverse pathologic characteristics, including advanced tumor stage and grade (p=0.036 and p=0.002, respectively), whereas this association was not significant for PAK4 expression (each p>0.05). Kaplan-Meier estimates showed that high expression of pPAK4S474 was associated with shorter recurrence-free survival in a subgroup with localized RCC and with cancer-specific survival in the total RCC cohort (log-rank test: p=0.001 and p=0.005, respectively), whereas PAK4 expression was not. Multivariate Cox regression analysis identified that high pPAK4S474 expression was an independent predictor of recurrence in the subgroup with localized RCC. Conclusions: pPAK4S474 may be a more accurate prognostic factor than total PAK4 in RCC patients. This marker would be useful for identifying patients with pathologically localized disease who may require further interventions. |
| Databáze: | Directory of Open Access Journals |
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