Clinical Significance Of Expression Galectin-3, Bcl-2, MMP-2 And K-ras In Laryngeal Carcinoma

Background: Laryngeal carcinoma is originated from the laryngeal mucosa epithelium. Laryngeal carcinoma most commonly affects men middle-aged or older who are smokers and who use alcohol. The peak incidence is in those aged 50-60 years. Laryngeal cancers account for approximately 1-2% of all new cancer diagnoses and 11% -12% of otorhinolaryngology cancer in our country. The incidence of laryngeal tumors is closely correlated with smoking, as head and neck tumors occur 6 times more often among cigarette smokers than among nonsmokers. The age-standardized risk of mortality from laryngeal cancer appears to have a linear relationship with increasing cigarette consumption. In addition, the pathogenesis of laryngeal cancer is also strongly associated with human papilloma virus infection and other factors.Laryngeal carcinoma is the most common ,higher morbidity malignant tumour in the northeast of our country. The high incidence of this disease can be seen not only in the developing country but also the developed country.At present,operation, chemo- treatment,radiation treatment are the three major theraphy method . But, we had to resolve these difficult problem, such as high toxic side effects of chemicotheraphy,tumor recurrence or low quality of life(dysphagia,suffocate)which caused by improper surgical operation ,etc.Therefore,tumor gene theraphy is the best treatment strategy with strongest development prospect.Studies have demonstrated that galectin-3 is highly expressed in many human malignant cancer,such as thyroid cancer,stomach cancer,breast cancer,liver cancer,bile duct cancer,prostate cancer,bladder cancer,etal.galectin-3 is related to the occurrence and development of many tumors. Some studies have proved that galectin -3 is also highly expressed in the head and neck cancer ,Galectin -3 has become a research hotspot.Galectin-3 is a member of a large family ofβ-galactoside-binding lectins and widely distributed among various normal tissues and tumor cells. Galectin-3 exhibits pleiotropic biological function, play an important role in many physiological and pathophysiological processes. Recent research has demonstrated that galectin-3 is associated with the tumor cell adhesion, proliferation, angiogenesis, and metastasis. Therefore, it is assumed that galectin-3 may become one of the attractive target genes in the diagnosis and therapeutic option for cancers.Galectin-3 and bcl-2 have similar important sequence, the sequence has characteristics of anti-apoptosis. Particularly lectin contains NWGR sequence, the same sequence highly conserved in the bcl-2 family, is a key to inhibit the activity of cell apoptosis. Galectin - 3 regulate cell growth and apoptosis, through tumor cell escaping way similar to Bcl - 2 to inhibit apoptosis.Galectin-3, a pleiotropic carbohydrate-binding protein, can selectively activate k-ras GTP.Because these two proteins are related to tumor cell resistance to apoptosis and progression of cancer,through research on galectin-3's potential function in the k-ras gene activation,we can find that galectin-3 through binding and activating wild-type k-ras gene plays a role in cancer, and suggest that some of the functions of galactose molecules, at least in part, participate in k-ras activation.Galectin-3 is the substrate of matrix metalloproteinase -2 and -9, galectin-3 can be decomposed by MMP to produce a molecular weight of 9 kU of amino acid residues and a molecular weight of 22 kU of carbohydrate recognition domains galectin -3 terminal fragment.mmp-2 participates in invasion and metastasis of human tumor. It is clear that the increasing the expression of mmp-2 is related to tumor evolution, and therefore the cracking of galectin-3 may play a role in tumor metastasis and invasion.The current study intends to clarify the tumor related genes bcl-2, mmp-2 and k-ras association with the function of galectin-3 expression, and how are those genes involved in the pathogenesis of laryngeal carcinoma.Methods:galectin-3,bcl-2,mmp-2and k-ras expression was studied using immunohistochemistry staining methods in laryngeal squamous cell carcinoma (LSCC) tissues of 32 patients, normal mucosa tissues of 32 cases, and polyp of vocal cord tissues of 10 cases. The relation of their expression with pathological grade, clinical staging and lymph node metastasis of LSCC was analyzed. The linear regression analysis was used.Results: Positive expression of galectin-3, bcl-2 and mmp-2 and k-ras mainly are limited in cytoplasm of the cell. their positive expression rates in normal mucosa tissues of 32 cases is 34.4%,0,9.4%,0 respectively, their positive expression rates in LSCC tissues of 32 cases is 62.5%,75%,81.25% respectively. their expression had statistic difference (p<0.05)in normal mucosa tissues and LSCC tissues . their expression had statistic difference (p<0.05)among normal mucosa tissues, polyp of vocal cord tissues and LSCC tissues. Expression of galectin-3and bcl-2 are related to pathological grade(p<0.05, expression of bcl-2 is related to clinical stages and lymph node metastasis of LSCC(p<0.05. the expression level of galectin-3 and bcl-2,galectin-3 and mmp-2, galectin-3 and k-ras had positive correlation in LSCC(r=0.993,0.989,0.992).Conclusions: The over expression of galectin-3,mmp-2 and k-ras are closely related to occurrence and development of the LSCC. The expression level of bcl-2 is correlated with occurrence,development,grade malignancy and rate of lymph node metastasis of LSCC. Co-expression of galectin-3,bcl-2,mmp-2 and k-ras are able to promote the pathogenesis of LSCC. Galectin-3 is possible to become a new target gene of LSCC therapeutic option, detection of galectin-3 gene may provides new theoretical basis for the early diagnosis, prognosis and gene therapy of laryngeal cancer.