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PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma.

ABSTRACT: Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. PAX5 methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0-136.3) in ESCCs and 0.3 (0-8.6) in adjacent normal tissues (P < 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; P = 0.005; 95% Confidence Interval (CI): 1.39-5.81] and overall survival (HR = 3.23; P = 0.002; 95%CI: 1.52-7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. PAX5 gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.

SUBMITTER: Kurimoto K

PROVIDER: S-EPMC5788430 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma.

Kurimoto Keisuke K Hayashi Masamichi M Guerrero-Preston Rafael R Koike Masahiko M Kanda Mitsuro M Hirabayashi Sho S Tanabe Hiroshi H Takano Nao N Iwata Naoki N Niwa Yukiko Y Takami Hideki H Kobayashi Daisuke D Tanaka Chie C Yamada Suguru S Nakayama Goro G Sugimoto Hiroyuki H Fujii Tsutomu T Fujiwara Michitaka M Kodera Yasuhiro Y

Epigenetics 20171127 10

Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identi ...[more]

PMID: 29099287

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Project description:Background:p53 isoform ?133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear. Patients and Methods:Expression of ?133p53 and ?133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR. Patients were divided into high- and low-expression groups according to the cutoff value determined by X-tile 3.6.1 software. Survival analysis was performed by the Kaplan-Meier method. Univariate and multivariate Cox survival analyses were applied to assess the hazard ratios (HRs). Results:Tissue ?133p53 expression and ?133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative ?133p53 expression and ?133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan-Meier curve and multivariate cox regression analyses revealed that the tissue and serum ?133p53/FLp53 ratios (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients and showed no statistical difference in receiver-operating characteristic curve (ROC) analysis, while serum ?133p53 showed no significant prognostic value. More importantly, the serum ?133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum ?133p53/FLp53 ratio (?2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum ?133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression. Conclusion:The serum ?133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.

Dataset Information

PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma.

Publications

PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma.

Similar Datasets

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