| Background:Colorectal cancer(CRC)is a common malignant tumor of the digestive system,which is pose a significant health harzard.The latest cancer data of China Cancer Center and American Cancer Center in 2017,it is reveal that the mortality rate of CRC went an apparent decline and incidence on a clear rise with early screening and new treatment methods,especially in younger patients(<50 years).A lot of studies also shows the large difference among molecular mechanisms,clinical prognosis and drug sensitivity on different anatomical sites of CRC.The molecular characteristics of left-sided colon cancer,such as chromosome instability(CIN),as often happen abnormal activation on the signal pathways of Wnt and EGF,and pathological classification mostly appeared well differentiated,hence easy diagnosis in the early stage of CRC and the prognosis better.However,the molecular features of right colonic carcinoma mainly reflected in high microsatellite instability(MSI),high methylation of CpG island(CpG Island Methylator Phenotype,CIMP)and a large number of key oncogenic gene mutation,pathological classification mostly appeared poorly differentiation,high ratio in advanced CRC,mucus components mainly in adenocarcinoma,easily give rise to complications,and worse prognosis.But the right colon cancer has better effect on chemotherapy and PD-L1target immunosuppressant.On the molecular mechanism of left and right colon cancer of current related studies mainly focus on chromosome instability,microsatellite instability and gene mutation,but there are few studies on the difference of gene transcription level.In addition,there’s controversy about the correlation between the clinicopathologic parameters and prognosis on LCC and RCC,exsiting related studies are mostly in small sample.We need to explore badly that is differences in gene expression levels and prognosis between left and right colon cancers,and different molecular expressions can help us improve accuracy on clinical diagnosis and treatment.Therefore,this study collected 3,106 patients with left and right colon cancer who were hospitalized in southern hospital from January 1,2008 to December 30,2016.The differences in relevant clinical and pathological parameters of colon cancer in different parts were compared,and the differences in survival conditions and the correlation prognosis research.The molecular mechanism of left and right colon cancer has been preliminarily revealed on transcriptome level.Experimental Method1.Collected 3106 left and right colon cancer specimens WHO were hospitalized from January 1.2008 to December 30,2016 with complete follow-up data,to make pathology diagnosis through WHO classification criteria of digestive system tumors(2010 edition);2.Large sample was analyze the parameters correlation and variations between gender,age,histological type,gross type,depth of infiltration,lymph node metastasis,distant metastasis,differentiation degree and clinical prognosis on LCC and RCC;3.There is analyzed on transcriptome chip data,the differentially expressed genes,and KEGG signal pathway enrichment with GSE41258 in the public database GEO of LCC and RCC4.The mRNA levels of TGF-beta,NF-kappa B and other signaling pathway related genes were differentially detected by q-pcr on the left and right colon cancer tissues respectively.5.Immunohistochemistry(IHC)has shown the difference in expression of INHBA gene of left and right colon cancer and the significance of its prognostic correlation.Results1.Left and right colon cancer and its location,gender and age:there were 3,106 patients with middle left colon cancer,1927(62.04%),1179(37.96%)patients with right colon cancer,and the incidence of left colon cancer was significantly higher than that of right colon cancer(P<0.05).There were 1219 cases(63.3%)of left colon cancer in male,708 cases(36.7%)of female,671 cases(56.9%)of right colon cancer in male and 508 cases(43.1%)of female.The incidence of left and right colon cancer in male was significantly higher than in female(P<0.05).The incidence of left and right colon cancer was not significantly different between the three groups(P>0.05).2.Left and right colon cancer type and histological type:49 cases of left colon cancer,23 cases of mass type(46.9%),21 cases of ulcer type(42.9%),and 5 cases of infiltration type(0.9%);There were 87 cases of right semicolon,35 cases of mass type(40.2%),35 cases of ulcer type(40.2%),and 17 cases of infiltration type(19.5%).Histological type dififerences:in the left colon cancer,there were 1785 cases(92.6%)of adenocarcinoma,109 cases(5.7%)of mucinous adenocarcinoma,29 cases(1.5%)of signet ring cell carcinoma,1 case(0.1%)of undifferentiated carcinoma,and 1 case(0.1%)of adenosquamous carcinoma.In the right colon cancer,there were 1035 cases of adenocarcinoma(87.8%),114 cases of mucinous adenocarcinoma(9.7%),27 cases of signet ring cell carcinoma(2.3%),l case of undifferentiated carcinoma(0.1%),and 1 case of adenosquamous carcinoma(0.1%).The left and rnght colon cancer showed significant differences in histological types(P<0.05).3.Left and right colon cancer with invasion depth,lymph node metastasis and distant metastasis:in left colon cancer,there were 32 cases of Tis staging(1.7%),130 cases of T1 staging(6.7%),105 cases of T2 staging(5.4%),1264 cases of T3 staging(65.6%),and 375 cases of T4 staging(19.5%).In the right half of colon cancer,there were 17 cases of Tis staging(1.4%),84 cases of T1 staging(7.1%),56 cases of T2 staging(4.7%),768 cases of T3 staging(65.1%),246 cases of T4 staging(20.9%),and there were differences in the depth of infiltration between left and right colon cancer patients(P<0.05).In left colon cancer,there were 1446 cases of NO staging(75%),296 cases of N1 staging(15.4%);and 182 cases of N2 staging(9.4%).In the right colon cancer,there were 835 cases(70.8%)of NO staging,187 cases of N1 stacging(15.9%),147 cases of N2 staging(12.5%),and there were differences between left ancd right colon cancer patients about NO stagi1ng and N1 staging.There was a difference between left and right coloin cancer in overall N staging(P<0.05).In left colon cancer,there were 1834 cases of MO stage(95.2%)and 91 cases of Ml stage(4.7%).In the right colon cancer,there were 1112 cases of IxMO stage(94.3%)and 65 cases of M1 stage(5.5%).There were differences in left and right colon cancer patients at stage MO(P<0.05),but no significant differences in left and right colon cancer patients at overall M staging(P>0.05).4.Degree of left and right colon cancer and differentiation:there were 286 cases of poorly differentiated adenocarcinoma(14.8%),1328 cases oi moderately differentiated adenocarcinoma(68.9%),and 279 cases of well differentiated adenocarcinoma(14.5%)in left colon cancer.There were 185 cases(15.7%)of poorly differentiated adenocarcinoma,797 cases(67.6%)of’moderately differentiated adenocarcinoma,and 175 cases(4.8%)of well differentiated adenocarcinoma in the right colon cancer.There was a difference between left and right colon cancer in the moderately differentiated adenocarcinoma(P<0.05).5.Left and right colon cancer and clinical prognosis:5-year overall survival rate of left colon cancer patients is 59.2%;The 5-year overall survival rate is 52.9%in right colon cancer patients,and the 5-year overall survival rate in LCC was higher than in RCC(P<0.05).6.GEO database GSE41258 KEGG signaling pathways(n = 390)data analysis results show that the cell cycle,extracellular matrix receptor interaction(ECM-receptor interaction),PI3K Akt signaling pathway,p53 signaling pathways,TNF signaling pathways,chemokine signaling pathways,the Hippo signaling pathway and Wnt signaling pathways in left and right colon cancer were significantly enriched.However,TGF-beta,NF-kappa B and other signaling pathways were significantly enrichment in the right colon cancer,but not in the left colon cancer.7.As the output in Q-PCR shows,the mRNA expression level of INHBA in the TGF-beta signaling pathway was significantly higher than in 12 related genes on the left colon,including TGF-beta and NF-kappa B.The IHC results showed that the expression level of INHBA protein in the left and right colon that is significantly higher than in the normal paired intestinal mucosa,and the expression level of INHBA in the right colon and cancer embolus in blood and lymph-vessel,vascular wall infiltration,and lymph node metastasis were significantly higher than in the left colon.In addition,the expression level of INHBA was closely related to the clinical stage,lymph node metastasis,blood and lymph-vessel invasion,vascular wall infiltration and distant metastasis of tumor and the overall survival(P<0.05).Conclusion1.There were significant differences in the parameters of left and right colon cancers including gender,age,histologic type,gross type,depth of infiltration,lymph node metastasis,distant metastasis,differentiation degree and clinical prognosis.2.At the transcriptome level,the expression disorders of target genes of TGF-beta,NF-kappa B and other signaling pathways may be involved in the occurrence and development of rnght colon cancer;3.The mRNA and protein expression levels of the target gene INHBA in the TGF-beta signaling pathway were significantly up-regulated in the right colon cancer;And its expression is closely related to clinical stage,lymph node metastasis,blood and lymph-vessel infiltration,vascular wall infiltration and distant metastasis of tumor and other malignant progression parameters and overall survival. |
PDF Full Text Request