title: Phosphorylated p38, a negative prognostic biomarker, complements TNM staging prognostication in colorectal cancer.
abstract: Phosphorylated p38 (p-p38) played a pivotal role in the regulation of disease progression and correlated with tumor prognosis. Here, we characterized the prognostic effect of p-p38 in colorectal cancer (CRC). Three hundred and sixteen CRC patients in stages I-III were recruited in this study. P-p38 expression was semi-quantitatively evaluated using tissue microarrays and immunohistochemistry staining. Overall survival (OS), disease-free survival (DFS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS) of patient subgroups, segregated by p-p38 expression level and clinical stage, were compared using Kaplan-Meier analysis. We found that p-p38 was overexpressed in 48.1 % (152/316) CRC tissues, whereas low or deficiently expressed in normal adjacent epithelia. Overexpression of p-p38 predicted poor OS (P < 0.001), DFS (P = 0.002), LFFS (P = 0.016), and DMFS (P = 0.025) in CRC. Importantly, patient subgroups in the early stage (stages I + II) and with low p-p38 had similar OS, PFS, LFFS, and DMFS probabilities to that of stage I, whereas those with high p-p38 were similar to stage III disease. In addition, for stage III disease, the subgroup with low p-p38 had a similar survival probability to that of stage I, whereas the subgroup with high p-p38 had the worst survival. Multivariate Cox analysis confirmed that p-p38 was indeed a significantly independent factor for death, recurrence, and distant metastases in CRC. Our results demonstrated that p-p38 was a negative independent prognostic factor for CRC. Complementing TNM staging with p-p38 might refine the risk definition more accurately for a subset of patients.
authors: Gastrointestinal Institute of Sun Yat-sen University, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancunerheng Road, Guangzhou, 510655, Guangdong, China.
authors: Xin-Juan
authors: XJ
authors: Fan
authors: Xiang-Bo
authors: XB
authors: Wan
authors: Xin-Hui
authors: XH
authors: Fu
authors: Pei-Huang
authors: PH
authors: Wu
authors: Dian-Ke
authors: DK
authors: Chen
authors: Pu-Ning
authors: PN
authors: Wang
authors: Li
authors: L
authors: Jiang
authors: Dao-Hai
authors: DH
authors: Wang
authors: Zhi-Ting
authors: ZT
authors: Chen
authors: Yan
authors: Y
authors: Huang
authors: Jian-Ping
authors: JP
authors: Wang
authors: Lei
authors: L
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D046888:Tissue Array Analysis; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D048051:p38 Mitogen-Activated Protein Kinases