| BACKGROUND&AIM:As we all know, Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer death throughout the world. According to statistics, it accounts for13%(1.6million) of the total cancer cases and18%(1.4million) of the deaths in2008. Lung cancer rates are increasing in countries such as China and several other countries. Overall, the5-year survival rate is approximately15%, whereas the5-year survival rate for patients of stage I with radically surgical resection is over70%. Therefore we need a more thorough study to know the biological behavior of lung cancer and to find some new detecting methods at the early stage. In order to achieve this, we use tumor marker in the present study.In previous study of our lab, we provide a novel method to detect free proteins that released to plasma by lung cancer tumor cells to establish lung cancer-related protein profiles in peripheral blood. First, we analyzed the proteins released into serum-free conditioned medium (CM) by lung cancer cells and its adjacent normal bronchial cells through short-time culture, and then we established lung cancer related protein database (over1200proteins), which includes Matrix metalloproteinase7(MMP-7). MMP-7has been found to perform several biological functions in tumor promotion, growth and metastasis. The aim of this study is to examine the protein levels of MMP-7in tumor tissue and peripheral blood of lung cancer patients, and evaluate its potential clinical value.METHODS:①Peripheral blood samples were obtained from114lung cancer patients and100healthy control subjects. MMP-7protein levels in the plasma were measured by enzyme-linked immunosorbent assay.②97lung cancer tissue specimens (found from the same114patients) were also examined by immunohistochemistry to determine the protein express of MMP-7.RESULTS:①ELISA results:The plasma protein levels of MMP-7in lung cancer patients(median=0.72ng/mL) were significantly higher than those in healthy control subjects (median=0.30ng/mL)(P<0.001).When the cutoff of MMP-7protein level was set at0.56ng/mL, the sensitivity and specificity of detecting lung cancer were62.3%and76.0%, respectively. However, the plasma protein levels of MMP-7in lung cancer patients did not statistically differ in age, sex, smoking status, tumor size, pathological classification, as well as lymphatic metastasis and stage (P>0.05).②IHC results:The MMP-7positive rates in lung cancer tissues was62.91%, and it is significantly higher than normal alveoli and bronchial tissues(P<0.001). The positive rates of MMP-7in lymphatic metastasis and low classification of tumor were significantly higher than those in non lymphatic metastasis and high+mediate classification (P value is0.017and0.025, respectively). But there are no other correlations between the MMP-7expression and the patients’other clinical characteristics, such as age, sex, smoking status, tumor size and stages (P>0.05).CONCLUSION:①The plasma protein levels and the expression of MMP-7increase in the peripheral blood of lung cancer patients and tumor tissues. It indicates that MMP-7plays a big role in tumor’s growth and metastasis as well as other members of MMPs. The expression of MMP-7in lung cancer tissues is higher in lymphatic metastasis and low classification patients. All of this shows that MMP-7is a potential outstanding tumor marker and prognostic factor for lung cancer patients and maybe a new target for drug thearapy.②The fact that no significant correlation between the protein levels of MMP-7and lung cancer patients’clinical characteristics were observed in this study warrants further analysis in larger samples. BACKGROUND:With the development of radiological techniques, more and more solitary pulmonary nodules (SPN) have been found. However, the diagnostic accuracy and diagnostic efficient are not satisfactory as the result of limited current diagnosis methods. Most patients still need surgical treatment and surgeons generally rely on intra-operative fast frozen section (FSD) technique to help deciding corrected diagnosis and operation strategy. But FSD also has its limitations. Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) Spectroscopy could serve as a diagnostic tool for detecting and discriminating different diseases, with the absorption of electromagnetic radiation from400cm-1-4000cm-1, is sensitive to changes in molecular compositions and structures. The aim of this preliminary study was to distinguish malignant and non-malignant lung tissues with ATR-FTIR spectroscopy.METHODS:60lung tissue samples were obtained from30patients underwent pulmonary lobectomy. Samples were examined with ATR-FTIR spectroscopy before histological diagnosis. Peak positions, intensities and full width at half maximum (FWHM) of each absorbent band were measured, and the relative intensity ratios were calculated. FTIR parameterrs of malignant and non-malignant samples of the two groups were compared. Normally, distributed data were analyzed with the t test; otherwise the Mann-Whitney U test was used. P<0.05was considered statistically significant. Canonical discriminant analysis (CDA) was used to distinguish malignant and non-malignant lung samples. Wilk’s lambda stepwise discriminant program was applied to help select variables that contribute most to the discriminant function. Two discriminant equations were established. Retrospective validation and leave-one-out cross-validation were also used to evaluate the discriminant power of the CD A. Sensitivity, specificity were calculated. Pathologic results as gold standard were compared with the CDA classification later.RESULTS:Of the two groups, peak positions of1640cm-1,1303cm-1,1120cm-1,1085cm-1were significantly different; peak intensities of1546cm-1,1460cm-1,1400cm-1,1165cm-1,1120cm-1, and relative intensity ratios of1743cm-1,1640cm-1,1546cm-1,1240cm-1,1120cm-1of the two groups were distinctly different from each other; The differences of FWHM1640cm-1,1460cm-1,1400cm-1,1303cm-1,1240cm-1,1165cm-1,1120cm-1,1085cm-1between the malignant and non-malignant sample groups were statistically significant.Functions of Canonical Discriminant Analysis were established as follows: Lmalignant=3.241X1+3.687X2+106.193X3+116.557X4-137.103Lnon-malignant=3.613X1+3.200X2+79.639X3+151.923X4-131.738X1represents FWHM at1303cm-1; X2signifies FWHM at1240cm-1; X3indicates peak intensity ratio at1120cm-1; X4presents as peak intensity at1546cm-1. The sensitivity and specificity of the CDA were all96.7%.CONCLUSIONS:ATR-FTIR spectroscopy is a promising method for detection of malignant lung tissue, and could be proved useful in lung tumor surgery. |
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