Journal Title
Title of Journal: Tumor Biol
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Abbravation: Tumor Biology
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Publisher
Springer Netherlands
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Authors: Fan Zhang Zhaoli Chen Pan Wang Xueda Hu Yibo Gao Jie He
Publish Date: 2016/01/16
Volume: 37, Issue: 7, Pages: 9323-9331
Abstract
The aim of this study is to search the most powerful prognostic factor from routine blood test for esophageal squamous cell cancer ESCC patients Multiple laboratory tests were evaluated including those reflecting red blood cell parameters hemoglobin Hb mean corpuscular volume MCV mean corpuscular hemoglobin concentration MCHC and red blood cell distribution width RDW platelet morphological parameters mean platelet volume MPV and platelet count PLT blood coagulation status Ddimer and tumor biomarker CA199 Known inflammatory indices NLR and PLR were also calculated A total of 468 patients who were diagnosed with ESCC between December 2005 and December 2008 were retrospectively analyzed in this study By utilizing univariate and multivariate Cox proportional hazard analyses we found that PLT and MPV were significantly associated with overall survival OS and diseasefree survival DFS of ESCC patients with optimal cutoff values of 212 and 106 respectively Moreover the combination of the preoperative PLT and MPV COPMPV was calculated as follows patients with both PLT ≥212 × 109 L−1 and MPV ≥106 fL elevation were assigned a score of 2 and patients with one or neither were assigned a score of 1 and 0 The COPMPV was an independent prognostic factor for OS hazard ratio HR 0378 95 confidence interval CI 0241 to 0593 P 0001 0/2 and DFS HR 0341 95 CI 0218 to 0534 P 0001 0/2 in multivariate analyses In subgroup analyses for early stages I and II and locally stage III advanced stage patients COPMPV was found significantly associated with OS and DFS in each group P = 0025 and P = 0018 for OS and P = 0029 and P = 0002 for DFS In conclusion we considered that COPMPV is a promising predictor for postoperative survival in ESCC patientsAmong the most lethal malignancies esophageal cancer EC ranks the sixth worldwide leading to approximately 400000 deaths in 2012 1 In China esophageal cancer is the fourth leading cause of all cancer deaths representing a major problem of public health in some highrisk rural areas 2 The dominant histopathological type of EC is squamous cell carcinoma ESCC in Chinese patients which covers 90 of all cases 3 Despite the progress in radical resection and adjuvant therapy radiation and chemotherapy ESCC still shows a poor 5year survival rate of less than 30 4 The tumor node metastasis TNM staging especially the status of lymph node metastasis is currently the best predictor for ESCC patient survival 5 Although several studies had identified certain survivalrelated biomarkers 6 7 8 they were less powerful and hardly able to be converted to clinical use Thus it is important to recognize effective and easyobtained biomarkers for ESCC prognosisIn the past decade platelet activation has been demonstrated as a crucial biological process in carcinogenesis and metastasis 9 10 11 Platelet count PLT and mean platelet volume MPV are two main characteristics to evaluate platelet activation 12 Patients with thrombocytosis have been reported to have worse prognosis in multiple solid tumors such as ovarian cancer 13 endometrial cancer 14 gastric cancer 15 and colorectal cancer 16 On the other hand high MPV reflected an abnormal rate of platelet production and stimulation 17 Recent studies revealed that MPV levels were relatively higher in tumor patients than in normal controls and associated with poor prognosis in some gastrointestinal neoplasms 18 19 20 However the predictive value of PLT combined with MPV for postsurgery survival in ESCC has not been yet investigatedIn this study we assessed and checked the prognostic value of preoperative PLT and MPV in 468 ESCC patients Moreover we took the utility of a novel prognostic system based on platelet activation termed combination of platelet count and MPV COPMPV which made a promising distinction between better and worse prognosis in both subgroups of early stages I and II and locally advanced stage stage III ESCC patientsPatients with histopathologically confirmed ESCC with no distal metastasis TNM stage I–III were enrolled in the study from December 2005 to December 2008 All patients underwent esophagectomy at the Cancer Institute and Hospital Chinese Academy of Medical Sciences CAMS with written informed consent The exclusion criteria were 1 severe complications or deaths occurred within 30 days after surgery 2 preoperative systemic inflammatory response syndrome SIRS 3 neoadjuvant radiotherapy or chemotherapy and 4 evidence of infection or autoimmune disease All patients underwent a careful preoperative evaluation including clinical history taking physical examination laboratory blood testing biochemistry complete blood cell counts coagulation status and serum tumor marker pulmonary function test and multiple radiography computed tomography CT or magnetic resonance imaging MRI Clinicopathological information of the patients were obtained from the medical records including age gender smoking history drinking status tumor location differentiation grade maximum tumor diameter lymph node metastasis TNM stage and history of adjuvant chemotherapy and radiotherapy The TNM stage was assessed according to American Joint Committee on Cancer AJCC staging manual seventh edition 21 Patients underwent adjuvant radio/chemotherapy after surgery according to TNM stages and family economic status The laboratory characteristics including hemoglobin Hb mean corpuscular volume MCV mean corpuscular hemoglobin concentration MCHC red blood cell distribution width RDW mean platelet volume MPV platelet count PLT Ddimer and CA199 were performed within 5 days prior to surgery The last followup date was July 9 2015 This study was approved by the medical ethics committee of the Cancer Institute and Hospital CAMSOverall survival OS was defined as follows the time from surgery to the time of patients’ death for any cause or the last followup date when the patient was known alive Diseasefree survival DFS was calculated from the date of operation to first tumor recurrence Neutrophillymphocyte ratio NLR/plateletlymphocyte ratio PLR was respectively defined as absolute neutrophil/lymphocyte count divided by absolute lymphocyte count Categorical variables were shown as frequency percentage while continuous variables were presented as the mean values ± standard deviation Unpaired t or χ 2 test was used to compare whether statistical differences between groups were significant The optimal cutoff values of all continuous variables were determined by receiver operating characteristic ROC curve We used univariate analysis to narrow down the list of possible prognostic factors Variables with P value 01 in univariate analysis were brought into multivariate Cox proportional hazard model to determine their independency Specifically the cutoff values of PLT and MPV were 212 ×109 L−1 and 106 fL respectively The COPMPV score was calculated on the basis of these two platelet characteristics Patients with both a higher platelet count ≥212 × 109 L−1 level and a higher mean platelet volume ≥106 fL level were grouped a score of 2 and patients with one or neither were grouped a score of 1 and 0 respectively KaplanMeier curves and logrank test were used to compare survival differences among groups All statistical analyses were conducted by SPSS 210 software IBM Corporation Somers NY USA P 005 was considered statistically significantA total of 468 patients were enrolled in this study including 376 men and 92 women The mean age of all patients was 595 ± 90 years median age 60 years range 36 to 81 Mean followup period was 491 ± 326 months range 32 to 1145 months Twohundred seventy 577 patients had died during the observation period The 5year overall survival rate was 450 for the whole cohort The distribution of TNM stages was stage I 46 98 stage II 199 426 and stage III 223 476 Mean PLT and MPV were 218 ± 65 × 109 L−1 range 52 to 611 and 106 ± 11 fL range 71 to 144 respectively Mean SD range levels of other selected laboratory variables or ratios were as follows Hb 145 gL−1 15 65 to 194 MCV 944 fL 51 767 to 1144 MCHC 342 gL−1 11 311 to 378 RDW 128 08 104 to 165 Ddimer 155 μg L−1 129 18 to 1522 CA199 1163 U mL−1 1383 035 to 14530 NLR 198 102 053 to 1100 and PLR 10966 4020 3279 to 41852
Keywords:
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