title: Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy.
abstract: The association between the expression of excision repair cross‑complementing gene 1 (ERCC1), thymidylate synthase (TYMS), ribonuleotide reductase M1 (RRM1), βIII‑tubulin (TUBB3), non‑muscle myosin II, myoglobin and MyoD1 in metastatic lung adenocarcinoma, and clinical outcomes with platinum‑based chemotherapy treatment is not well‑established. Recently, increasing attention has been focused on the involvement of ERCC1, TYMS, RRM1 and TUBB3 in the development of drug resistance. There has been less research into the role of muscle myosin II, myoglobin and MyoD1 in the pathogenesis of lung cancer, although these genes are known to have important functions within tumor cells. In the current study, malignant pleural effusion from 116 patients with untreated lung adenocarcinoma diagnosed between 2011 and 2012, were collected. The protein expression levels of ERCC1, TYMS, RRM1 and TUBB3 were evaluated with immunocytochemistry and western blot analysis. The expression levels of non‑muscle myosin II, myoglobin and MyoD1 were measured in a subset of 50 patients, treated with platinum‑based chemotherapy. The association of each of these seven factors with one another, as well as with patient survival were analyzed. Immunohistochemistry demonstrated that the percentage of pleural fluid samples from patients with lung adenocarcinoma expressing ERCC1, TYMS, RRM1 and TUBB3 was 37, 36.2, 82.7 and 69.8%, respectively. In the subset of 50 patients in whom the remaining factors were analyzed, the percentage expressing non‑muscle myosin II was 48%, for myoglobin the figure was 40% and for MyoD1 it was 38%. There was a positive correlation between each pair of the above seven molecules with the exception of TYMS and RRM1. Expression of ERCC1, TYMS, TUBB3, non‑muscle myosin II, myoglobin and MyoD1 genes was associated with decreased survival in patients with metastatic lung adenocarcinoma. Expression of ERCC1, TYMS, TUBB3, non‑muscle myosin II, myoglobin and MyoD1 was also associated with decreased survival rates of patients with lung adenocarcinoma treated with platinum‑based chemotherapy. These factors may be used as clinical biomarkers to predict the biological behavior and chemoresistance of tumor cells, and the survival of patients with lung carcinoma.
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Haijiao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Lab Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine, The Commonwealth Medical College, Scranton, PA 18905, USA.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology and Lab Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Zhengtong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Second Affiliated Hospital of China Medical University, Shenyang, Liaoning 110011, P.R. China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110013, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D009211:Myoglobin / Q000235:genetics / Q000378:metabolism; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D010984:Platinum / Q000008:administration & dosage; D016066:Pleural Effusion, Malignant / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D009211:Myoglobin; C498585:TUBB3 protein, human; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D010984:Platinum; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C000600377:TYMS protein, human; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D024462:Myosin Type II