title: Personalizing risk stratification by addition of PAK1 expression to TNM staging: improving the accuracy of clinical decision for gastroesophageal junction adenocarcinoma.
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.
authors.affiliation: Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China; Department of Oncological Radiotherapy, The People's Hospital of Gaozhou, Gaozhou, Guangdong, China; Cancer Research Center, Shantou University Medical College, Shantou, China.
authors.forename: Zongtai
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zou
authors.forename: Liangxi
authors.initials: L
authors.lastname: Xie
authors.forename: Hongcai
authors.initials: H
authors.lastname: Chen
authors.forename: Yuping
authors.initials: Y
authors.lastname: Chen
authors.forename: Sai-Ching Jim
authors.initials: SC
authors.lastname: Yeung
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D047368:Tumor Burden; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: PAK1 kinase; cancer staging; gastroesophageal junction adenocarcinoma; inadequate lymphadenectomy; lymph nodal metastasis; personalized therapeutics