title: Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer.
abstract: Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using micro-array. Further studies are needed to collect the data of the mRNA markers used in clinical practice.
authors.affiliation: Department of Internal Medicine, Graduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Inn-Wen
authors.initials: IW
authors.lastname: Chong
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Chang
authors.forename: Huang-Chou
authors.initials: HC
authors.lastname: Chang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Yu
authors.forename: Chau-Chyun
authors.initials: CC
authors.lastname: Sheu
authors.forename: Jong-Rung
authors.initials: JR
authors.lastname: Tsai
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Shah-Hwa
authors.initials: SH
authors.lastname: Chou
authors.forename: Mee-Sun
authors.initials: MS
authors.lastname: Tsai
authors.forename: Jhi-Jhu
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Shiu-Ru
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D024161:Collagen Type XI / Q000096:biosynthesis* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000090803:mu-Crystallins
chemical_list: D014408:Biomarkers, Tumor; C000716469:CRYM protein, human; D024161:Collagen Type XI; C121535:ITGA11 protein, human; D039001:Integrin alpha Chains; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D000090803:mu-Crystallins; D010744:Phosphoric Monoester Hydrolases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes