Overexpression of circulating c-met messenger RNA is significantly correlated with nodal stage and early recurrence in non-small cell lung cancer.
BACKGROUND
The c-met receptor and its ligand hepatocyte growth factor have been shown to be involved in tumor invasiveness and metastasis. Overexpression of c-met has been demonstrated in lung cancer tissues and cell lines, but the expression of c-met in peripheral blood (circulating c-met) has not been addressed. The molecular monitoring of circulating c-met could be helpful for selecting patients for adjuvant therapy.


OBJECTIVE
To investigate the expression of circulating c-met in non-small cell lung cancer (NSCLC) patients and to assess its prognostic implications.


METHODS
We quantified the levels of c-met messenger RNA (mRNA) in paired tumor and normal lung tissues and their peripheral bloods in 45 patients with NSCLC by real-time polymerase chain reaction (PCR). The expression status of c-met protein in tumor tissues was further evaluated by immunohistochemistry.


RESULTS
c-Met mRNA was significantly higher by 1.5 to 11 times in 34 of 45 tumor tissues (75.5%) than it was in their normal counterparts by real-time PCR. A comparison of this assay to immunohistochemistry suggested that real-time PCR was more sensitive than immunohistochemistry (27 of 45 tumor tissues, 60.0%) for the detection of c-met (p = 0.016). Of these patients with overexpression of c-met in tumors, 67.6% (23 of 34 patients) expressed higher amounts of circulating c-met by 1.4 to 8 times that of the normal control subjects. In addition, overexpression of circulating c-met was significantly correlated with nodal (N) stage (p = 0.011), but weakly correlated with tumor (T) stage (p = 0.056) and overall stages (p = 0.054) in patients with NSCLC. However, no correlations were found among circulating c-met and other factors such as age, gender, and pathologic types. Moreover, by univariate analysis, circulating c-met overexpression and pathologic stages (including T and N stages) were the most important factors correlated with early recurrence (p < 0.05). Only the circulating c-met remained as an independent predictor of early recurrence (hazard ratio, 3.94; 95% confidence interval, 1.17 to 13.33; p = 0.027) after Cox regression multivariate analysis.


CONCLUSIONS
Overexpression of circulating c-met is significantly correlated with the N stage and early recurrence. Moreover, early recurrence is frequently noted in patients with overexpression of circulating c-met, indicating that circulating c-met is an independent negative prognostic indicator in NSCLC.
Cheng
Tian-Lu
TL
MedicoGenomic Research Center, Kaohsiung Medical University, 100 Shih-Chuan First Rd, Kaohsiung, 807 Taiwan.
Chang
Mei-Yin
MY
Huang
Sung-Yu
SY
Sheu
Chau-Chyun
CC
Kao
Eing-Long
EL
Cheng
Yu-Jen
YJ
Chong
Inn-Wen
IW
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000097:blood
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met