Year-end Sale % OFF 
Abstract
The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase) family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs) and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both). Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001) and in adjacent nontumor mucosae (r = 0.460, P<0.001). The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64) and PHLPP2 (85.9%, 55/64). However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138) and 82.6% (114/138) of tumor tissues, respectively (P<0.0001, both). The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all). It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS) in HSCC patients (P = 0.004, P = 0.008, respectively). Multivariate analysis revealed that PHLPP1 was an independent prognostic factor for OS. This study indicates that, in HSCC, aberrant expressions of PHLPP1 and PHLPP2 are common events, and loss of PHLPPs might identify patients with poor prognostic outcomes.
Highlights
Hypopharyngeal squamous cell carcinomas (HSCCs) account for approximately 5–15% [1] of all head and neck cancers; they are the most aggressive and have the worst prognosis in the head and neck area [2]
Our quantitative reverse transcription polymerase chain reaction assays revealed that the mean mRNA levels of PHLPP1 were 0.0037 ± 0.0024 in HSCC tissues and 0.0060 ± 0.0035 in adjacent nontumor mucosae (P
Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues and in adjacent nontumor mucosae (r = 0.460, P
Summary
Hypopharyngeal squamous cell carcinomas (HSCCs) account for approximately 5–15% [1] of all head and neck cancers; they are the most aggressive and have the worst prognosis in the head and neck area [2]. The poor prognosis of HSCC might be because of the lack of early detection and high rate of metastasis [3]. Many molecules, such as SIRT1, DBC1 [4], Beclin-1, LC3 [5], and Caveolin-1 [6], have been evaluated as candidate biomarkers for HSCC, but none have been widely used in practice because of the lack of understanding of the molecular mechanisms involved in HSCC development, progression, and treatment response [7]. Studies of novel and more effective molecular biomarkers of HSCC prognosis and progression are necessary
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
