Abstract
Gastroesophageal junction adenocarcinoma (GEJA) is an aggressive malignancy with an alarmingly rising incidence. TNM staging is widely used by oncologists to stratify prognosis as well as direct therapeutic strategies. However, inadequate lymphadenectomy is frequently encountered for GEJA and largely confounds prognosis resulting from TNM staging. Thus, a molecular biomarker, which can accurately forecast the risk of nodal metastasis in patients with inadequate lymphadenectomy, is required to guide precisely clinical decision. In this study, bioinformatics and pathological analysis identified that p21 protein-activated kinase 1 (PAK1) is associated with lymph nodal metastasis of GEJA. The PAK1 H-score was lower in the patients with negative lymph nodes than that in patients with positive (metastatic) lymph nodes (6.865 ± 3.376, 9.370 ± 2.530, respectively; p < 0.001). The PAK1 H-score in lymph nodes was positively correlated with that in primary tumors (PTs; p < 0.001; r = 0.475). PAK1 H-scores in PTs had the best performance based on its area under the receiver-operating characteristic (ROC) curve compared with PAK1 H-scores in lymph nodes, histological grade, lymph nodal metastasis status, tumor size, depth of tumor, TNM stage and number of resected lymph nodes. Multivariate Cox proportional hazard and Fine and Gray models showed that histological grade 3, Charlson comorbidity index > 7 and high PAK1 expression in PTs were associated with significantly increased risk of recurrence and cancer-related death. In conclusion, high PAK1 expression in PTs is predictive of node metastasis and can be easily integrated in the clinical decision process for personalized therapeutics of GEJA.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: 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.