TY - JOUR
T1 - Personalizing risk stratification by addition of PAK1 expression to TNM staging
T2 - Improving the accuracy of clinical decision for gastroesophageal junction adenocarcinoma
AU - Li, Zongtai
AU - Zou, Xiaofang
AU - Xie, Liangxi
AU - Chen, Hongcai
AU - Chen, Yuping
AU - Yeung, Sai Ching Jim
AU - Zhang, Hao
N1 - Publisher Copyright:
© 2014 UICC.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - Cancer staging
KW - Gastroesophageal junction adenocarcinoma
KW - Inadequate lymphadenectomy
KW - Lymph nodal metastasis
KW - PAK1 kinase
KW - Personalized therapeutics
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U2 - 10.1002/ijc.29167
DO - 10.1002/ijc.29167
M3 - Article
C2 - 25159681
AN - SCOPUS:84920938719
SN - 0020-7136
VL - 136
SP - 1636
EP - 1645
JO - International journal of cancer
JF - International journal of cancer
IS - 7
ER -