| Background:Lung cancer remains the leading cause of cancer mortality in men and women in the worldwide which is one of the diseases that influenced human health. The lesions were always diagnosed at the advanced stage. Some patients even missed the best time of treatment. Contributing factors of this phenomenon may include the early symptom of lung cancer is similar to pneumonia, early diagnosis is not precise and sensitive. It is necessary by means of biology to find tumor biomarkers which are of strong specificity and high sensitive. Glycosylation of proteins is one of the most important PTMs, with more than half of all human proteins estimated to be glycosylated, they involved in numerous essential biological functions including cell proliferation, differentiation and migration, cell-cell integrity and recognition, cell-matrix, and immune modulation. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. In our study, by the technique of lectin microarray, we detected the transformation of lung cancer patients serum glycoprotein glycan with variety classes, and different pathology periods. Hopefully to find biomarkers related to lung cancer’s occurrence and progression which might provide references for early diagnosis.Method:Chapter 1 overviewed the research progress of glycomics, the alteration of protein glycosylation in lung diseases, human humoral glycoproteomics research, lectins and lectin microarray technique, and the future prospects in this research field. Chapter 2 and 3 studied the alteration of protein glycosylation of small cell lung cancer, squamous cell lung carcinoma and adenocarcinoma. Lectin microarrays were used to probe the alteration of protein glycosylation in serum from patients with three kinds of lung cancer compared with serum from healthy volenteers and patients with benign pulmonary disease. We prepared a serum microarray which could further verify our discovery in lectin arrays. Lectin blotting was used to further validate the lectins which bind to the proteins of pathological lung cancer.Result:In SCLC group, when compared with HV serum group, there are 3 lectins (Jacalin, WFA, STL) showed alterations in LD-SCLC serum group and 5 lectins (GSL-I, LCA, HHL, NPA, UEA-Ⅰ) showed alterations in ED-SCLC serum group. When compared with BPD serum group, there are 9 lectins (e.g. SNA, LEL, GSL-Ⅰ, DBA, LTL, HHL, NPA) showed alterations in LD-SCLC and 7 lectins (e.g. SNA, NPA, PHA-E, EEL, GSL-Ⅰ, STL) showed alterations in ED-SCLC serum group. The glycan structures which altered in SCLC are T antigen, Tn antigen, terminating GalNAcα/β1-3/6Gal etc. In ADC group, when compared with HV serum group, there are 14 lectins (e.g. LCA, WGA, PWM, MAL-Ⅰ, WFA, PTL-Ⅰ) showed alterations in ADC-ES serum group and 16 lectins (e.g. LCA, WGA, PWM, UEA-Ⅰ, SNA, AAL, EEL) showed alterations ADC-AS serum group. When compared with BPD serum group, there are 13 lectins (e.g. LCA, WGA, PWM, UEA-Ⅰ, BS-Ⅰ, MAL-Ⅰ, PTL-Ⅱ, ConA) showed alterations ADC-ES serum group and 14 lectins (e.g. LCA, WGA, PWM, UEA-Ⅰ, BS-Ⅰ, SNA, WFA) showed alterations ADC-AS serum group. The glycan structures which altered in ADC are a-D-Man, Fuca-1, Fuca-1,6GlcNAc, α-D-Glc etc. Meanwhile, there are 8 lectins (LCA, WGA, PWM, EEL, NPA, MPL, AAL, LEL) showed alterations both in ADC-ES and ADC-AS. In SCC, when compared with HV serum group, there are 11 lectins (e.g. LCA, BPL, EEL, DBA, NPA, GSL-I, MPL) showed alterations in SCC-ES serum group and 11 lectins (e.g. PSA, EEL, DBA, NPA, GSL-I, HHL, MPL) showed alterations SCC-AS serum group. When compared with BPD serum group, there are 8 lectins (e.g. MAL-Ⅱ, HHL, EEL, MPL, BS-Ⅰ, PTL-Ⅱ) showed alterations SCC-ES serum group and 8 lectins (e.g. SJA, EEL, DBA, NPA, MPL, BS-Ⅰ) showed alterations SCC-AS serum group. The glycan structures which altered in SCC areβ-Gal, Galβ-1, High-Mannose, Fucal-2Galβ1-4Glc(NAc) etc. Meanwhile, there are 3 lectins (EEL, MPL, BS-Ⅰ) showed alterations both in SCC-ES and SCC-AS. In these alterations, blood group B antigen which recognized by EEL significantly upregulated in SCLC, ADC, SCC. αGalNAc which recognized by GSL-Ⅰ significantly upregulated in NSCLC. On the contrary, it showed down regulation in SCLC. And some other glycan structures which recognized by BS-Ⅰ, UEA-Ⅰ showed different level of expression. In conclusion, screening characteristic glycans in different type of lung cancer and different pathologic stages of lung cancer will provide references for early diagnosis of lung cancer. |
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