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ObjectiveToinvestigateRUNX3genepromoter methylationincolorectal carcinogenesis and its prognostic significance. MethodsThe protein expression of RUNX3 was detected by immunohistochemistry and the methylation status of the RUNX3 was determined by methylation-specific PCR (MSP) in colorectal normal mucosa and cancer tissue from 65 patients,and adenoma from 28 patients.5-year overall survival rate was analysed according to RUNX3 methylation status from cancer patients.Kruskal-Wallis rank sum test,x2 or Fisher's exact test,Log-rank test and multivariable Cox regression analysis were used for statistical analysis.ResultsThe protein expression of RUNX3 gene in adenoma and cancer was 85％ (24/28) and 52％ (34/65),significantly lower than that in normal mucosa 94％ (61/65)( x2 =4.328,P =0.037 ; x2 =16.675,P =0.000),the difference between adenoma and cancer tissue was no statistic significance (x2 =3.266,P =0.071 ).No case showed RUNX3 methylation in normal mucosa,methylation rates in adenoma and cancer tissue were 21％ (6/28) and 35％ (23/65),significantly higher than in normal mucosa (P =0.000 ),but there was no statistic significance between adenoma and cancer tissue (x2 =1.766,P =0.183).The protein expression rate with RUNX3 methylation was 67％ (4/6) in adenoma,unmethylation 91％ (20/22) (P =0.191 ).The protein expression rate with RUNX3 methylation was 26％ (6/23) in cancer,unmethylation was 88％ (28/32).The presence of RUNX3 methylation was related to loss of protein ( x2 =9.810,P =0.002 ).5-year total survival rate with methylation in cancer was significantly lower with unmethylation ( x2 =5.87,P =0.016 ).Multivariate analysis showed RUNX3 methylayion wasanindependentprognosticfactoramongthefactorsanalyzed(P=0.033 ).ConclusionsRUNX3 methylation is important genetic event in colorectal carcinogenesis,possibly related to protein downregulation,and an independent prognostic factor for colorectal carcinoma.
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Targeted therapy combined with chemotherapy has achieved great success in palliative treatment for metastatic colorectal cancer.Recent studies gave more emphasis on new fields,such as maintenance treatment,adjuvant treatment and the prognostic & predictive biomarker.These advances have been gradually changing the treatment strategies for colorectal cancer.The latest advances on the targeted therapy for colorectal cancer from the 2010 Annual Meeting of American Society of Clinical Oncology are reviewed below.
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MicroRNA (miRNA),an abundant class of small non-coding RNA,are abundant in the central nervous system where they play important roles in the neuronal development and plasticity.Moreover,the relationship between miRNA dysfunction and neurological diseases become more and more apparent.Recent studies show that the misregulated expression of miRNA out of control is closely related to the development of glioma.In this review we discussed the progress on the study of miRNA in Glioma.
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Objective:To isolate cancer stem cells from cervical carcinoma and to identify their biological characteristics. Methods:Tumor specimens were obtained from 19 cervical cancer patients at stages ⅠA-ⅡB. Primary cells were cultured in tumor sphere medium (TSM) after mechanical dissociation combined with enzymatic digestion. A series of assays were used to identify the characteristics of the sphere forming cells derived from primary culture. Colony formation was observed by limiting dilution method. MTT assay was used to assess proliferation inhibition by paclitaxel and doxorubicin. Cell surface markers were analysed by fluorescence-activated cell sorter (FACS). The expression of stemness-related genes, drug resistance-related genes, and oncogenes were detected by RT-PCR and Western blotting. Tumorigenicity was evaluated by subcutaneous injection of 1×10~5 sphere-forming cells into nude mice. The tumor formation capability was recorded and pathological classification was performed.Results:After 10 to 15 d culture, the formation of non-adherent spheres could be observed in 8 out of 19 primary tumor cells. The formation ratio was increased with the increase in clinical staging. Sphere-forming cells had colony formation capability. Paclitaxel (100 nmol/L) and doxorubicin (100 nmol/L) inhibited the proliferation of these cells by (77.65±6.46)% and (48.00±7.15)%, respectively. The difference was significant (P<0.01). FACS detection results indicated the phenotypes of sphere-forming cells were CD34~-CD105~-CD44~+CK17~+. RT-PCR detection indicated that spheres expressed stemness-related genes (Oct4 and Piwil2), drug resistance gene ABCG2, and oncogenes (c-myc, sox-2 and stat3). Western blotting further indicated stemness-related protein (Oct4 and Piwil2) expression in spheres. Tumors appeared in all animals at 12 weeks after subcutaneous injection of 1×10~5 sphere forming cells and exhibited a high degree of similarity with the primary tumor in cervical cancer patients. Conclusion:Human cervical cancer stem cells were successfully isolated,which provided a useful model for individualized therapy and evaluation of the therapeutic efficacy for cervical cancer patients.
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Objective To evaluate clinical value of tumor biomarkers in ascitic fluid and serum in differentiating benign from malignant ascites and their correlation. Methods From July 2006 to July 2009,67 patients with ascites undergone abdominal paracentesis in Renmin Hospital of Wuhan University were enrolled in the study and divided into malignant and benign groups according to their etiology. Levels of tumor biomarkers in ascitic fluid and serum were determined and their correlation were analyzed. Diagnostic sensitivity and specificity of tumor markers were evaluated. Results There was statistically significant difference in levels of cancer antigen 199 (CA199) in serum and ascitic fluid between the malignant group and the benign one ( P ＜ 0. 01 ), and level of cancer embryonic antigen (CEA) significantly increased in ascitic fluid (P ＜ 0.05 ). Levels of CA199 and CEA in serum were significantly higher than those in ascetic fluid in the benign group (P ＜ 0. 01 and P ＜ 0. 05 ), and level of CA125 was significantly lower in serum than that in ascitic fluid (P ＜ 0. 01 ). Level of alpha-fetal protein (AFP) in serum significantly correlated with that in ascitic fluid in the benign group (r =-0. 992, P ＜0. 01 ). In the malignant group, levels of CA199, CEA and CA125 were significantly higher in ascitic fluid than those in serum (P ＜0.05 or P ＜0. 01 ). Levels of CA199 and CEA in serum significantly correlated with those in ascetic fluid in the malignant group (r =0. 746 and 0. 572, respectively, P ＜0. 01 ), and level of AFP in serum also correlated with that in ascetic fluid (r=0. 384, P ＜0. 05). Ratios of levels of CA199 and CEA in ascetic fluid to those in serum (F/S) were significantly higher in the malignant group than those in the benign group (P ＜0.05 or P ＜0.01). Use of combination of CA199, CEA and CA125 determinations showed a higher sensitivity and specificity in differential diagnosis for benign and malignant ascites (P ＜0.05). Conclusions Determinations of CA199 and CEA are beneficial for differentiating benign ascites from malignant one. Determinations of tumor biomarkers in serum can not fully replace those in ascetic fluid. Combined determinations of CA199, CEA and CA125 can increase their sensitivity and specificity in diagnosis for malignant ascites.
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Objective To explore the clinical value of combined detection of CA15-3, TSGF, OPN and CA125 in the diagnosis and treatment of breast cancer. Methods The serum specimens from 187 patients with breast cancer (cancer group) were collected, tumor markers CA15-3 and CA125 were detected with electrochemiluminescence method, TSGF was detected with chemocolorimetry, and OPN was detected with enzyme-linked immunosorbent assay. Compared with 50 cases of patients with benign breast disease (control group), The relationship between these marker and clinical stage, recurrence and metastasis of breast cancer were analyzed. Results The serum levels of CA15-3, CA125, TSGF and OPN in cancer group were significantly higher than those in control group (P ＜0.05). Four markers in high clinical stage(Ⅲ and Ⅳ stage)[(83.21±28.67), (89.13±32.34), (278.66±137.23) U/ml and (97.4±11.7) ng/ml, respectively] were higher than those in low stage( Ⅰ and Ⅱ stage) [(60.03±19.35), (58.21±17.56), (155.79±113.11) U/ml and (77.5±10.81) ng/ml,respectively] (P ＜0.05), and those in lymphnode metastasis patients and in recurrence patients were significantly higher than those in corresponding groups (P ＜0.05). The sensitivity and specificity of the combined detection of four tumor markers were 96.3 % (180/187) and 80.0 % (40/50), respectively. The average time of combined detection of serum tumor markers was 2 months ahead of the mammographic features in the recurrence patients with breast cancer. Conclusion The dynamic combined detection of CA15-3, TSGF, OPN and CA125 are better markers for monitoring recurrence and metastasis of breast cancer,which are benefit to early diagnosis and interference.
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Human epididymis gene product 4 (HFA)mRNA highly expressed in oarian cancer tissue and the quantity was associated with the type of the ovarian cancer;The serum HF4 had the same specificity and sensitivity in the early diagnosis of oarian cancer compared with CA125 ,and the HF4 had an advantage over theCA125 in that it was less frequently positive in patients with nonmalignant disease;the combination of HE4 andCA125 yielded higher sensitivity ;The serum tumor marker HFA is an excellent marker for determining responseto treatment and for the detection of early recurrence of disease in patients with epithelial ovarian cancer; HE4 isnot only a serological tumor biomarker but also a target for gene-based therapy of ovarian cancer.
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Objective To investigate the expression of CEA, NSE and CYFRA21-1 in lung cancer, and the significance of combined determination of three tumor markers in the detection of lung cancer. Methods CEA, NSE and CYFRA21-1 levels in serum of 65 patients with lung cancer, 50 patients with benign lung diseases and 38 normal adults were measured by enzyme linked immunosorbent assay (ELISA). The association of CYFRA21-1, NSE, and CEA level with the type of lung cancer in pathology were also studied. Results In comparison, the serum levels of CEA, CYFRA21-1 were increased more obviously in patients with lung cancer than that of patients with benign lung diseases and the normal adults (P<0.01). The levels of serum and the sensitivity of CEA, NSE and CYFRA21-1 were related to pathology type. The sensitivity and specificity increased by combined measurement of CEA, NSE, and CYFRA21-1. Conclusion These findings suggest that the serum CEA, NSE and CYFRA21-1 levels is increased in patients with lung cancer, and the increasing extents is not same in lung cancer with different pathology types. CEA, NSE and CYFRA21-1 are significant in adjuvant diagnosis of lung cancer.
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Objective To study the clinical values of neuron-specific enolase(NSE) as serum tumor marker in lung cancer.Methods The serum NSE levels in 96 patients with lung cancer,60 patients with begnign pulmonary disease and 60 healthy controls were measured by using enzyme-linked immunosorbent assay.Results The levels of NSE in serum in patients with lung cancer was significantly higher than those in healthy subjects and patients with begnign lung disease(P0.05).The effective rate of chemotherapy were 87.10%,40.00% and 66.67%, 33.33% in patients with SCLC and NSCLC,respective for NSE positive and negative ones(P
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Small cell lung cancer (SCLC) is one of the most fatal cancers in humans and many factors are known to be related to its poor prognosis. Immunohistochemical (IHC) stainings were done on SCLC specimens in order to investigate the prognostic value of the apoptosis-related gene expression and the tumor proliferative maker, and the relationships among these IHC results and patients clinical characteristics, chemoresponsiveness, and survival were analyzed. The medical records of 107 patients were reviewed retrospectively. IHC stainings for p53, bcl-2 and Ki-67 expressions were performed in the 66 paraffin-embedded biopsy samples. Sixty-six out of the 107 patients were evaluable for response rate and survival. The overall response rate was 75% (95% Confidence Interval=74-76%) and the median survival time was 14 months. The median survival time of limited stage was 16 months and that of extensive stage was 10 months. The prevalence of p53, bcl-2 and Ki-67 expression was 62%, 70%, and 49%, respectively. There were no correlations among the immunoreactivities of p53, bcl-2 and Ki-67 with clinical stage, chemoresponsiveness or overall survival. The clinical stage was the only prognostic factor influencing survival. The expression rates of p53, bcl-2, and Ki-67 were relatively high in SCLC without any prognostic significance. The exact clinical role of these markers should be defined through further investigations.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Pequeñas/metabolismo , Inmunohistoquímica , Antígeno Ki-67/análisis , Neoplasias Pulmonares/metabolismo , Análisis Multivariante , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Análisis de Supervivencia , Biomarcadores de Tumor/análisis , Proteína p53 Supresora de Tumor/análisisRESUMEN
Objective To search for the biomarker used to determine gastric cancer by the application of protein mass spectrometry analysis. Methods The relative contents of serum proteins were detected of 38 patients with gastric cancer and 82 healthy people by IMAC3 (CipherGen Inc.) chip and proteinchip. Results At the M/Z values range from 1 723Da to 14 048Da, 18 kind of protein contents are obviously different between the two groups. In the learning mode, all the 120 testers were correctly distinguished, both the sensitivity and specificity reached to 100%. While in the test mode, 31 patients and 81 control people were correctly distinguished, the accuracy were 81 6%(31/38) and 98 8%(81/82), respectively. Conclusion Gastric cancer can be quickly and exactly diagnosed by this method with high sensitivity and specificity. That will be widely used in clinical application