[Significance of combined determination of CK19mRNA, carcinoembryanic antigen, neuron-specific enolase, and tissue polypeptide antigen in peripheral blood of patients with lung cancer].
OBJECTIVE
Cellular keratin, an indicator for cancer cell in circulation gains increasing attention. Although CK19mRNA as a gene marker used to identify micro-metastasis is of relatively high practical value, it lacks specificity and sensitivity in diagnosis of cancer. The aim of this study is to evaluate whether the combined detection of CK19mRNA with other tumor markers, such as carcinoembryanic antigen(CEA), neuron-specific Enolase(NSE), tissue polypeptide antigen(TPA), would improve the diagnosis of lung cancer.


METHODS
The expression level of CK19mRNA in peripheral blood mononucleated cells (PBMCS) was determined by RT-PCR, The levels of CEA, NSE, and TPA in serum were determined by enzyme-linked immunosorbent assay (ELISA) and time-resolved fluorometry(TRF) in 91 patients with lung cancer, 33 with benign lung diseases (BLD) and 50 healthy controls. The data was analyzed by t test and chi 2 test.


RESULTS
The positive rates of CK19mRNA, CEA, NSE, and TPA in lung cancer group (49.5%, 65.9%, 67.0%, and 83.5%, respectively) were remarkably higher than in BLD group(24.2%, 9.0%, 15.2%, and 9.0%, respectively) and in healthy control group (10.0%, 4.0%, 8.0%, and 6.0%, respectively) (P < 0.01). The positive rate of CK19mRNA was not statistically different in various histological subtypes (P > 0.05). Although the positive rate of CK19mRNA appeared to be associated with the clinical stage (stage I + II: 44.4%, stage III: 48.4%, stag IV: 54.2%), there was no statistical significance among the three groups (P > 0.05). The serum level (microgram/L)/positive rate of CEA(3.5/27.8%, 5.1/35.5%, and 8.5/58.3%, respectively), NSE (12.5/33.3%, 15.3/41.9%, and 24.7/58.3%, respectively), and TPA (1.1/44.4%, 1.8/58.1%, and 3.6/66.7%, respectively) in stage I + II, III, and IV appeared to be associated with the clinical stages of lung cancer, but no statistical significance among the three groups (P > 0.05). Combined detection of three or four tumor markers yielded significant higher effective accuracy in diagnosis of lung cancer than that of any of two tumor markers or single tumor marker (P < 0.05). In addition, the results showed that TPA, CEA, and NSE were relatively specific for squamous cell carcinoma (76.7%), adenocarcinomas (83.3%), and small-cell lung cancer (79.2%), respectively.


CONCLUSIONS
The combined measurement of CK19mRNA with CEA, NSE, and TPA can increase diagnosis rate of lung cancer, can also provide potent diagnosis basis for treatment.
Pan
Qiang-rong
QR
Clinical Experimental Research Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P. R. China. Phanbao@China.com
Zhang
Xing
X
Xu
Ze-feng
ZF
Zheng
Shu
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics*; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood*; D019396:Tissue Polypeptide Antigen / Q000097:blood*
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D019396:Tissue Polypeptide Antigen; D007633:Keratins; D010751:Phosphopyruvate Hydratase