Granulocyte-macrophage-colony stimulating factor in patients with colorectal cancer

Granulocyte-macrophage-colony stimulating factor (GM-CSF) belongs to the group of glycoproteins called colony-stimulating factors (CSFs). It has been shown that the activity of CSFs is not limited to the hematopoietic cells but can also affect the proliferation of colon carcinoma cell lines. The purpose of this investigation was to compare the serum level of GM-CSF in colorectal cancer patients to a control group, to assess the level of GM-CSF in relation to the level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to define the sensitivity, the specificity and the predictive values of GM-CSF in colorectal cancer. In this study, the serum level of tumour markers was measured in 30 patients with colorectal cancer and in 20 healthy subjects. GM-CSF was assayed using ELISA system, CEA and CA 19-9 were measured by MEIA. The serum levels of CEA, CA 19-9 and GM-CSF were higher in the patients with colorectal cancer than in the control group. The sensitivities of CEA (63%) and CA 19-9 (56%) were lower than the GM-CSF sensitivity (80%). The specificities of tumour markers were 70% (CEA, GM-CSF) and 75% for CA 19-9. The GM-CSF predictive v values were higher than the CEA and CA 19-9 values. These results suggest that GM-CSF may be useful as tumour marker in colorectal cancer, but further studies are needed.     

肿瘤标志物联合检测在乳腺癌早期诊断中的应用

目的：探讨肿瘤标志物癌胚抗原（CEA）、糖链抗原19-9（CA19-9）、糖链抗原15-3（CA15-3）联合检测在乳腺癌早期诊断中的应用价值。方法：检测87例乳腺癌患者,55例乳腺良性肿瘤患者和35例健康人血清中CEA、CA19-9、CA153等肿瘤标志物的水平及3种标志物不同组合对乳腺癌的阳性检出率。结果：乳腺癌患者3种肿瘤标志物显著高于正常对照组及乳腺良性肿瘤组（P〈0.01）。3项标志物不同组合对不同分期乳腺癌检出的敏感性均高于单项标志物。其中CEA＋CA199＋CA153组合的检出敏感性较其他组合均高,特别是对早期患者检出率明显提高。结论：CEA＋CA199＋CA153联合检测能提高乳腺癌的早期诊断率。     

血清多肿瘤标志物蛋白芯片检测在乳腺癌诊断中的价值

目的:探讨血清多肿瘤标志物蛋白芯片检测系统在乳腺癌诊断中的临床价值。方法:临床确诊的乳腺癌患者307例为乳腺癌组,非乳腺癌的其他恶性肿瘤患者495例为对照组。应用多肿瘤标志物蛋白芯片检测系统检测12种肿瘤标志物水平,评价血清肿瘤标志物的在乳腺癌组与对照组之间的差异。结果:CA153,CEA,Free-PSA这三项指标为诊断乳腺癌的独立相关因素(P<0.05),比较三项指标ROC曲线下面积可见,CA153对于鉴别乳腺癌准确性更高,其敏感性、特异性分别为78.92和56.14,女性乳腺癌患者Free-PSA可见明显升高,对乳腺癌有特殊提示意义,手术前后标志物CA199、CA242、Ferrin、CA125水平差异有统计学意义。结论:在临床常用的肿瘤标记物中,CA153,CEA,Free_PSA水平的升高与乳腺癌发生独立相关,其中CA153具有更高的诊断准确性,Free_PSA水平升高对乳腺癌的诊断有特别提示意义。     

Immunoassay of nine serological tumor markers on a hydrogel-based microchip

A prototype test-system for simultaneous quantitative assay of nine tumor markers in blood serum was developed. The main constituent of the test-system is an OM-9 biochip containing immobilized antibodies against nine oncomarkers: α-fetoprotein (AFP), carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), total and free forms of prostate-specific antigen (PSA_tot and PSA_free), and neuron-specific enolase (NSE). The biochip-based two-step sandwich immunoassay procedure for carrying out simultaneous quantitative determination of nine tumor markers in patients’ blood serum was proposed. The main analytical characteristics of the method were obtained. The results suggest that the prototype of the test-system could be a promising instrument for clinical application. The test-system prototype was tested using blood serum samples of oncological patients (252 samples) and healthy donors (185 samples). Increased concentrations of one or more tumor markers above the normal level were found in 76.6% cases of oncological patients and only in 6% cases of healthy donors. For colorectal cancer patients, application of modern statistical methods of data processing in medical research, i.e., receiver operating characteristics analysis (ROC curve) and logistic regression, indicated that the simultaneous assay of nine markers on biochips showed much more diagnostic significance (area under the ROC curve, AUC, was 0.84) than a traditional assay of two tumor markers, CEA and CA 19-9 (AUC = 0.59). The developed biochip-based test-system can be recommended for both the estimation of people’s health, e.g., for standard medical examination, and tracking the tumoral process in the postsurgical period or after specific tumor treatment.     

肿瘤标志物联合检测在乳腺癌早期诊断中的应用

目的:探讨肿瘤标志物癌胚抗原(CEA)、糖链抗原19-9(CA19-9)、糖链抗原15-3(CA15-3)联合检测在乳腺癌早期诊断中的应用价值。方法:检测87例乳腺癌患者,55例乳腺良性肿瘤患者和35例健康人血清中CEA、CA19-9、CA153等肿瘤标志物的水平及3种标志物不同组合对乳腺癌的阳性检出率。结果:乳腺癌患者3种肿瘤标志物显著高于正常对照组及乳腺良性肿瘤组(P<0.01)。3项标志物不同组合对不同分期乳腺癌检出的敏感性均高于单项标志物。其中CEA+CA199+CA153组合的检出敏感性较其他组合均高,特别是对早期患者检出率明显提高。结论:CEA+CA199+CA153联合检测能提高乳腺癌的早期诊断率。     

Tumor markers in pancreatic cancer: a comparative clinical study between CEA, CA 19-9 and CA 50

Seventy-eight patients were evaluated to ascertain the usefulness of markers CA 19-9 and CA 50 in diagnosing pancreatic cancer, using a less specific marker (CEA) as reference. Three groups were considered: a) 36 controls; b) 22 patients with benign obstructive jaundice; c) 20 patients with pancreatic cancer. Preoperative blood samples were obtained to ascertain CEA (E.I.A.), CA 19-9 (R.I.A.) and CA 50 (T.R.-F.I.A.). Serum concentrations of the various markers were significantly higher for patients with pancreatic cancer in comparison with the other groups, at cut-offs of 10 ng/ml (CEA), 100 ng/ml (CA 19-9) and 170 U/ml (CA 50). The sensitivity of CA 19-9 (94%) and CA 50 (88%) was much greater than that of CEA (30%). The specificity of the three markers in patients with pancreatic cancer, with respect to the control group, was 100% and this figure is reduced with respect to the group suffering from benign obstructive jaundice (CEA: 90%; CA 19-9: 88% and CA 50: 87%). Diagnostic results (sensitivity, specificity, positive predictive value (P.P.V.) and negative predictive value (N.P.V.] did not significantly increase with respect to CA 19-9 and CA 50 when considered individually. It is concluded that the serum concentrations of CA 19-9 and CA 50 showed high sensitivity and specificity as markers of pancreatic cancer with respect to the other groups, pointing towards clinical routine clinical use of both markers. In addition, a comparative study of the literature has been made and prospects for short-term development and concrete applications for early and reliable diagnosis have been highlighted.     

Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer

To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.     

Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer

Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen, and thus plays a key role in the migration of tumor cells. MMP-2 activity is inhibited by its tissue inhibitor (TIMP-2). The imbalance between MMPs and TIMPs may facilitate progression of cancer cells. The aim of this study was to compare the clinical importance of MMP-2 and TIMP-2 to that of classical tumor markers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the diagnosis of gastric cancer (GC) by calculating the diagnostic criteria and estimating the levels of MMP-2, TIMP-2, CEA and CA 19-9 in GC patients in relation to clinicopathological features of cancer. We found that serum levels of MMP-2 and TIMP-2 were significantly lower, whereas serum tumor markers were higher, in GC patients than in healthy subjects. Moreover, concentrations of TIMP-2 and CEA correlated with gastric wall infiltration, while CA 19-9 levels correlated with gastric wall infiltration and the presence of nodal metastasis. None of the proteins tested was found to be an independent prognostic factor for GC patients' survival. The percentage of true positive results of TIMP-2 (61%) was higher than those of MMP-2 (54%) and the classical tumor markers CEA (21%) and CA 19-9 (31%). The highest diagnostic sensitivity was observed for the combined use of TIMP-2 with MMP-2 (77%). The results suggest the greater importance of serum MMP-2 and TIMP-2 than of the classical tumor markers CEA and CA 19-9 in the diagnosis of GC. But this issue requires further investigation.     

Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis

Abstract

Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.

Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.

Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0?ng/ml for CEA and 305.0?U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p?=?0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p?=?0.007).

Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.     

新辅助化疗与营养支持对老年结肠癌患者T 细胞，COX-2 及tM2-PK水平的影响

目的：探讨新辅助化疗与营养支持综合治疗对老年结肠癌患者血清肿瘤标记物水平、COX-2 及生活质量影响及临床意义。 方法：选取我科收治的老年结肠癌患者80 例,根据治疗方案不同分为对照组与试验组。对照组常规行结肠癌根治切除术,试验组 应用FOLFOX3 方案。比较两组患者血清肿瘤标记物CEA 及CA19-9 水平、COX-2 水平及CD4+、CD8+及tM2-PK 水平。结果：与 治疗前相比,治疗后试验组和对照组CEA 及CA19-9 水平降低（P<0.05),COX-2、tM2-PK 水平降低（P<0.05),CD4+及CD4+/CD8+ 水平降低（P<0.05),CD8+水平升高（P<0.05)。与对照组比较,试验组COX-2、tM2-PK 水平、CD4+、CD8+水平改善明显优于对照组, 差异具有统计学意义（P<0.05),而CEA 及CA19-9 水平组间比较,差异无统计学意义（P>0.05）。结论：新辅助化疗与营养支持综合 治疗可杀伤老年结肠癌患者全身不可见转移肿瘤细胞,控制病情,临床疗效理想。     

血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值分析

摘要 目的：探讨与分析血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断价值。方法：2019年8月到2022年5月选择在本院诊治的消化道恶性肿瘤患者150例作为消化道恶性肿瘤组,同期选择在本院体检的健康人群150例作为健康组。采集两组人群的血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）、C-反应蛋白（CRP）含量,调查患者的病理特征并判断诊断价值。结果：消化道恶性肿瘤组的血清CEA、CA19-9、CRP含量都高于健康组（P<0.05）。消化道恶性肿瘤组的CEA、CA19-9、CRP阳性率为54.7 %、58.7 %、60.7 %,高于健康组的3.3 %、4.0 %、4.7 %（P<0.05）。在消化道恶性肿瘤组中,不同组织学分化、临床分期、淋巴结转移患者的血清CEA、CA19-9、CRP含量对比有差异（P<0.05）。血清CEA、CA19-9联合CRP诊断为阳性113例,在健康组中诊断为阳性3例,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性分别为75.3 %（113/150）和98.0 %（147/150）。结论：消化道恶性肿瘤患者多伴随有血清CEA、CA19-9、CRP的高表达,病理特征与血清CEA、CA19-9、CRP含量存在相关性,血清CEA、CA19-9联合CRP在消化道恶性肿瘤的诊断敏感性与特异性都比较好。     

CA 72-4 compared with CEA and CA 19-9 as a marker of some gastrointestinal malignancies

The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA 72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.     

The clinical relevance of tumor marker CEA, CA 19-9 in regional chemotherapy of hepatic metastases of colorectal carcinoma

Up to December 1986, 50 patients with documented hepatic metastases from colorectal carcinoma were treated with 5-fluoro-2-deoxyuridine (FUDR) using Infusaid pumps. The response of liver metastases to regional chemotherapy was studied by computerized tomography (CT) and carcino-embryonal antigen (CEA), and/or CA 19-9 antigen serum assays. Preoperative CEA values were pathological in 94% of the patients but only 48% had a pathological concentration of the antigen CA 19-9 of over 37 U/ml. The course of CEA and CA 19-9 in combination with the arterial angio-CT reflected the response of liver metastases to regional chemotherapy. A decrease or normalisation of CEA and CA 19-9 after the beginning of therapy is an indication of partial or complete remission of metastases (68% of the patients showed lowered CEA serum values). If the marker continues to rise in serum this is a danger signal of progression of liver metastases or of extrahepatic tumor spread if the tumor stage in the liver remains unchanged.     

Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseases

The current best serum marker for pancreatic cancer, CA 19-9, detects a carbohydrate antigen on multiple protein carriers. Better knowledge of the protein carriers of the CA 19-9 antigen in various disease states may lead to improved diagnostic tests. To identify proteins that carry the CA 19-9 antigen, we immunoprecipitated the CA 19-9 antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifications, we confirmed the presence of the CA 19-9 antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 antigen on the four proteins across various patient groups (pancreatic cancer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the carrier proteins of an important functional glycan and the rate at which the glycan is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein carriers of glycans and assess the diagnostic value of measuring glycans on individual proteins.     

The significance of CA19-9 tumor antigen in the serum of patients with carcinomas

The concentration of serum CA19-9TM in 101 patients with colorectal adenocarcinoma (CRC), and 109 patients with carcinomas of lung, breast, stomach and pancreas and hepatoma, and 40 normal healthy controls including an equal number of smokers and nonsmokers were determined by solid phase radioimmunoassay of CA19-9 assay kits (Centocor). Of the normal sera, only 1 out of 40 (2.5%) was over 37.6 U/ml. No significant difference of CA19-9 levels was found between smokers (14.4 +/- 9.0 U/ml) and non-smokers (16.0 +/- 10.2 U/ml) of normal control. In patients sera, the mean value of CA19-9 levels was significantly higher in patients with Dukes B (P less than 0.05) and in patients with Dukes C and D (P less than 0.001) than the normal healthy control (15.2 +/- 10.2 U/ml). Analysis of serum CEA concentrations has shown a similar result in patients with all Dukes staged CRC. The CA19-9 levels was also significantly elevated in patients with gastric carcinoma, lung carcinoma, hepatoma, and especially in patients with pancreatic carcinoma (P less than 0.0001). The levels of CA19-9 elevated in 50% (22/44) of patients with advanced CRC while the elevation was 8 of 43 (18.6%) patients with localized CRC. A comparison of CA19-9 and CEA assays showed no correlation (r = 0.125) between the two assays. Although the CA19-9 assay (26.4%) was less sensitive than the CEA assay (51.7%), the specificity of CA19-9 assay (97.5%) was better than that of CEA assay (87.5%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple tumor marker elevation in androgen ablation-refractory prostate cancer with long-term response to metronomic chemotherapy: a case report

Outcomes in hormone-refractory prostate cancer are very poor. The time from progression to death is only 12-19 months. We present the case of a 69-year-old man with hormone-refractory prostate cancer and bone metastases treated with metronomic chemotherapy (cyclophosphamide based). He had had a colon adenocarcinoma ten years before. The atypical features of this case were an unusually long-lasting response to metronomic chemotherapy and an increase in serum levels of some non-prostate-specific tumor markers (CEA and CA 19-9) that was not related to a relapse of colon cancer. We hypothesize a potential role of hypoxia inducing CA 19-9 and CEA expression in tumor cells, which may predict the development of progressive resistance to antiangiogenic therapies.     

血清CEA、CA19-9、CYFRA21-1与结直肠腺癌的相关性分析

目的:探究血清癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原19-9、细胞角蛋白19片段(cytokeratin19 fragements,CYFRA21-1)与结直肠腺癌的病理相关性。方法:选择于我院接受治疗的80例结直肠腺癌患者为病例组,选择同期于我院接受治疗的50例良性结直肠病变患者为良性对照组,选择我院体格检查的50例健康个体为对照组,分别采集三组个体的血样并进行CEA、CA19-9以及CYFRA21-1水平的检测,并比对三组个体上述因子阳性表达率、因子水平,同时分析三种因子同结直肠腺癌患者TNM分期相关性,最后探究三种因子对结直肠腺癌的诊断价值。结果:(1)以CEA≥2.805μg/L、CA19-9≥39 U/m L、CYFR21-1≥3.3 ng/mL为临界值,结果显示病例组CEA阳性率51.25%,CA19-9阳性率31.25%,CYFR21-1阳性率40.00%,明显高于良性组的10.00%、20.00%和10.00%,高于对照组的8.00%、12.00%和2.00%(P<0.05);(2)比较显示病例组患者的CEA、CA19-9以及CYFR21-1水平明显高于良性对照组以及对照组(P<0.05),良性对照组CEA、CA19-9以及CYFR21-1水平明显高于对照组(P<0.05);(3)比较显示IV期结直肠腺癌患者CEA、CA19-9以及CYFRA21-1水平明显高于III期以及I+II期(P<0.05),III期三种因子水平明显高于I+II期(P<0.05);(4)CEA对结直肠腺癌诊断一致性71.25%,灵敏度65.00%,特异度90.00%;CA19-9诊断一致性46.25%,灵敏度35.00%,特异度80.00%;CYFRA21-1诊断一致性55.00%,灵敏度46.67%,特异度80.00%;联合诊断一致性95.00%,灵敏度95.00%,特异度95.00%。结论:血清CEA、CA19-9以及CYFRA21-1对结直肠腺癌具有较明确的诊断价值,不同病理分期患者中表达差异明显,可以考虑将联合诊断作为结直肠腺癌鉴别方式之一,推广于临床中。     

肺癌患者血清CEA，CA19-9，CA125 及CA153 围手术期动态监测的临床 意义

目的:探讨动态监测肺癌患者围手术期血清CEA、CA19-9、CA125及CA153水平变化的临床意义。方法:随机选取2014年5月至2015年5月收治的肺癌患者58例为研究对象,另选取同期在我院接受体检的健康人群15例为对照组。分别测定肺癌患者手术前及术后1天、1周、1个月、3个月的血清CEA、CA19-9、CA125、CA153水平,并与对照组的上述各血清肿瘤标志物进行比较。结果:肺癌患者术前空腹血清CEA、CA19-9、CA125、CA153水平明显高于对照组,差异具有统计学意义(P0.01)。肺癌患者术后1天、1周、1个月及3个月的血清CEA、CA19-9、CA125、CA153水平明显低于术前,差异具有统计学意义(P0.05)。肺癌患者术后1个月的平均空腹血清CEA、CA19-9、CA125、CA153水平高于术后3个月平均水平,但差异不具有统计学意义(P0.05)。结论:对肺癌患者的血清CEA、CA19-9、CA125、CA153水平进行围手术期动态监测有助于评估手术治疗效果。     

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients

The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary.     

Heterogeneity in antigenic expression and radiosensitivity in human colon carcinoma cell lines

Summary A panel of human colon carcinoma cell lines were characterized regarding both antigenic heterogeneity and variations in radiosensitivity. Monoclonal antibodies were used to study the expression of carcinoembryonic antigen (CEA), gastrointestinal cancer antigen (GICA or CA 19-9) and carcinoma-associated antigen (CA-50). Radiosensitivity was studied with the clonogenic survival technique. Three cell lines, LS 174T, HCTC, and SW 1116 stained positive for all three antigens. HT-29 was positive for CA 19-9 and CA-50 whereas Caco-2 was positive for CEA and CA 19-9. The cell lines SW 620 and LIM 1215 only stained positive for one of the antigens, CA-50 and CEA, respectively. In nearly all positive cases the stainings were very heterogeneous with mixtures of positive and negative cells. One exception was the HCTC cells which stained homogeneously for the CA 19-9 and CA-50 antigens. The neuroendocrinelike COLO 320 cells were negative in all cases. The radiosensitivity varied strongly between the cell lines with D_q-values between 0.8 and 1.9, extrapolation numbers between 2.0 and 4.7, D_o-values between 1.1 and 2.8. The surviving fraction at 2 Gy varied between 0.3 and 0.7 with HCTC as the most radiosensitive and HT-29 as the most radioresistant cell line. Thus, there were differences in antigenic expression and intrinsic radiosensitivity between the cell-lines and antigenic heterogeneities within each cell line. The analyzed panel of cell lines will be valuable in studies of dose-effect relations for monoclonal antibodies labeled with toxic radionuclides simulating both antigenic heterogeneity and variations in radiosensitivity.