| Colorectal cancer is the most common gastrointestinal malignancy. Its morbidity in recentyears has increased significantly and particularly for colon cancer. Thus the proportion ofcolon and rectal cancer has changed significantly, particularly in areas of high incidence ofcolorectal cancer. But when the whole country is concerned, rectal cancer still accounts for60%～70%of colorectal cancer. For low incidence of colorectal cancer areas, such as India,Senegal and Eastern Europe, the incidence of rectal cancer is still higher than colon cancer.Low rectal cancer makes up most of rectal cancer, which is a major feature of our country.Generally speaking, male are susceptible to owe rectal carcinoma, and incidence of male andfemale is1.5:1to2.0:1. The proportion of male and female incidence is closer in our countryfrom1.3:1to1.4:1. It is the third most common malignant cancer worldwide. The morbidityand mortality of colorectal cancer in western developed countries is much higher than that indeveloping countries and underdeveloped areas, and the morbidity and mortality of colorectalcancer in our country appeared significantly increased in recent years.Surgery is the primary method of treatment for colorectal cancer, but the high rate ofrecurrence and/or metastasis after surgery hinders a patient’s recovery, even withpostoperative chemotherapy and/or radiation therapy. Currently, the gold standard fordetermining postoperative treatment and prognostication for colorectal cancer patients isclinicopathological TNM staging by AJCC and UICC. Nevertheless, the TNM stage offerslittle help in the treatment of an individual patient. In addition, it is not understood why onlysome patients respond to therapy or have a good clinical outcome and others not. Therefore,understanding treatment failure and determining a good prognostic marker still remain animportant goal in the management of colorectal cancer patients. Some genetic changes mayhave a prognostic role in colorectal cancer, but thus far only the prognostic value of K-rasmutations in response to cetuximab therapy of metastatic colorectal cancer has been translatedinto the clinic. In addition, chromosomal and microsatellite instability have been associatedwith the clinical outcome of colorectal cancer patients. Nevertheless, despite the efforts todetermine molecular markers for individualized colorectal cancer treatments, none have beenintroduced into clinical practice. Therefore, the aim of this study was to find a potential diagnostic marker that could be used to predict the prognosis of colorectal cancer patients aftercurative surgery.Secreted protein acidic and rich in cysteine (SPARC, also known as osteonectin), bestknown for its role in tissue remodeling, wound repair, cell migration and angiogenesis, hasbeen widely studied in the biology of solid tumors. Although SPARC is expressed by differenttypes of cancers, the divergent functions of SPARC expression are cell type specific. HighSPARC expression has been associated with enhanced tumor growth, metastasis and poordisease prognosis in various malignancies including prostate, breast and esophageal cancers.Among studies of human colorectal cancer, its value as a prognostic marker and its function intumorigenesis remains elusive. Here, in the present study, SPARC expression was assessed toanalyze its prognosis in colorectal cancer patients using tissue microarrays byimmunohistochemistry.SPARC is highly expressed in the various malignant tumors, and associated withtumorigenesis, invasion and metastasis. Its mechanisms can be summaried into three areas:(1)degradation of the extracellular matrix. Extracellular matrix degradation is an important stepof the migration for tumor cells. SPARC degraded matrix protein through the induction of thesynthesis of a variety of proteases to impair its barrier function, so as to promote the migrationof tumor cells;(2) anti-adhesion. Cell separation is the beginning of tumor invasion of thesurrounding tissue and distant metastasis. It is a key role in the process of malignantprogression;(3) promote angiogenesis.Integrin1(ITGB1, CD29) is a member of the integrin family and is comprised of18a and8transmembrane subunits, they form at least24different heterodimeric receptors for celladhesion to extracellular matrix proteins. Integrins activate various protein tyrosine kinasesthrough focal adhesion kinase (FAK), Src-family kinases and serine-threonine kinases, inorder to regulate cell functions, such as proliferation, migration, invasion and survival. ITGB1functions as mediator of cell and extracellular matrix signaling in cell proliferation, apoptosisand survival. It has been reported that high ITGB1expression is associated with poorprognosis of patients with invasive breast, lung and pancreatic cancer. However, its value as aprognostic marker, as well as its correlation with clinical significance, has been rarely studiedin colorectal cancer patients.This experiment was based on the clinical data, postoperation recurrence and treatment ofpatients with colorectal cancer. Samples were produced with tissue microarray technology.Then, we explored the expression of SPARC and ITGB1in colorectal cancer patients, as wellas examined its relationship with clinicopathological features and prognosis in colorectal cancer patients.The results obtained showed the expression of SPARC is higher in colorectal cancer thannormal mucosa. Gender, age, bowel wall invasion and postoperative chemotherapy were notsignificant associated with SPARC expression. Lymph node metastasis, distant metastasis,CEA and CA19-9were significantly correlated with the expression of SPARC. MultivariateCox regression analysis showed that: bowel wall invasion [hazard ratio (HR),2.331;95%confidence interval (CI),1.153-4.711; P=0.018], lymph node metastasis (HR,2.059; CI,1.566-2.707; P<0.001), distant metastasis (HR,4.263; CI,2.672-6.802; P<0.001), CA19-9(HR,1.595; CI,1.019-2.498; P=0.041) and SPARC expression in stromal cells (HR,0.654; CI,0.409-1.048; P=0.028) were independent prognostic factors for overall survival factor. Fordisease-free survival factor, bowel wall invasion (HR,1.842; CI,1.012-3.350; P=0.045),lymph node metastasis (HR,1.590; CI,1.270-1.991; P<0.001), distant metastasis (HR,2.917;CI,1.925-4.421; P<0.001) and SPARC expression in stromal cells (HR,0.536; CI,0.359-0.802; P=0.002) were all independent prognostic factors for disease-free survival factor.Bisides, patients with higher SPARC expression showed longer over survival and disease-freesurvival than low SPARC expression.The expression of ITGB1is higher in colorectal cancer than normal mucosa and adenoma.With the development of TNM stages, expression of ITGB1increased significantly. Gender,age, bowel wall invasion, CEA and CA19-9were not significantly associated with ITGB1expression. Lymph node metastasis and distant metastasis were significantly correlated withthe expression of ITGB1. Multivariate Cox regression analysis showed that: bowel wallinvasion (HR,2.126; CI,1.140–3.963; P=0.018), lymph node metastasis (HR,1.900; CI,1.472-2.452; P<0.001), distant metastasis (HR,4.000; CI,2.517-6.357; P<0.001) and ITGB1expression (HR,1.782; CI,1.365-2.328; P<0.001) were all independent prognostic factors foroverall survival factor. For disease-free survival factor, bowel wall invasion (HR,1.726; CI,1.057-2.821; P=0.029), lymph node metastasis (HR,1.696; CI,1.380-2.084; P<0.001), distantmetastasis (HR,3.447; CI,2.310-5.143; P<0.001) and ITGB1expression (HR,1.707; CI,1.377-2.118; P<0.001) were all independent prognostic factors for disease-free survival factor.Bisides, patients with higher ITGB1expression showed shorter over survival and disease-freesurvival time than low ITGB1expression (P<0.001).The results implied that SPARC was a good novel molecular for target therapy in colorectalcancer patients and ITGB1was a bad prognostic marker for colorectal cancer patients. Theexperimental study of function of this molecular in vitro and vivo also spawned a number ofnew basic research scientific issues and provided a solid foundation for the future researchprojects. |
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