Do CA 19-9 and TPA play a minor role as compared to AFP in diagnosing primary hepatocellular carcinoma?

This study was undertaken in order to compare the ability of 4 tumour markers to discriminate between liver cirrhosis patients with or without hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA 19-9 and tissue polypeptide antigen (TPA) were determined in 63 patients with liver cirrhosis and in 25 patients with HCC in liver cirrhosis. All 4 serum markers were found to be increased in a number of liver cirrhosis patients, regardless of the presence of HCC. AFP was found to be more elevated in HCC patients as compared to the other group; no difference was observed for CA 19-9, CEA and TPA. A significant correlation was detected in HCC patients between AFP and TPA. Significant correlation were detected in all except HCC patients between liver function tests and TPA. We can conclude that AFP determination remains as yet the only suitable marker able to detect HCC in liver cirrhosis. The newly introduced serum marker CA 19-9 is, as previously reported, unhelpful for CEA. TPA can in some instances (i.e. in the absence of an important hepatic cell necrosis or cholestasis) provide a clue to neoplastic growth.     

Tumor markers--personal experience. The use of tumor markers for cancer of digestive organs]

This review is concerned mainly with our experience in the use of tumor markers for cancer of digestive organs from study of tumor markers by the author over the past 20 years. Development of a radioimmunoassay for highly sensitive detection of alpha-fetoprotein (AFP) by Ishii et al. in 1971 enhanced the usefulness of screening for early hepatocellular carcinoma (HCC) occurring in the course of liver cirrhosis. PIVKA-II, reported as a highly specific tumor marker for HCC, was thought to be less available for detection of early HCC occurring in the course of liver cirrhosis in comparison with AFP. Carcinoembryonic antigen (CEA), a most popular and useful tumor marker for cancer of digestive organs, was frequently positive in sera of colorectal cancer patients who had no subjective complaint or physical sign. This experience supported employment of CEA as a routine screening test for colorectal cancer. A survey of routine examinations of serum CA 19-9 for a period of one month in the clinical laboratory of our hospital proved that 92% of the positive cases of low-level CA 19-9 from 37 U/ml to 75 U/ml were noncancerous. This result indicated that the cut-off value of 37 U/ml employed for serum CA 19-9, which had been evaluated as a specific and highly sensitive tumor marker for pancreatic cancer and bile duct cancer, was too low. Accordingly, it was thought necessary to investigate a change of cut off value and reevaluate CA 19-9 for pancreatic cancer and bile duct cancer in comparison with other tumor markers of carbohydrate antigen such as CA 50, sialyl SSEA-1. From our experience in the use of tumor markers, the combination assays of fetal protein such as AFP, CEA, basic fetoprotein (BFP) and carbohydrate antigen, such as CA 19-9 and CA 50, for routine examination of tumor marker, are recommended for effective screening of cancer of digestive organs.     

甲胎蛋白、癌胚抗原和糖链抗原19-9联合检测诊断消化系统恶性肿瘤的价值分析

目的 探讨甲胎蛋白(AFP)、癌胚抗原(CEA)和糖链抗原19-9(CA19-9)联合检测对消化系统恶性肿瘤的诊断价值.方法 回顾性分析300例消化系统恶性肿瘤患者和108例消化系统良性病变患者的临床资料,记录患者的血清AFP、CEA和CA19-9水平,评价其诊断效能.结果 肝癌患者的血清AFP、CEA和CA19-9水平均高于肝硬化患者,胃癌、胰腺癌和结直肠癌患者的血清CEA和CA19-9水平分别高于胃溃疡、胰腺炎和溃疡性结肠炎患者,差异均有统计学意义(P<0.05).单项检测中,AFP对肝癌的诊断敏感度(78.5%)高于CEA和CA19-9(P<0.05);CA19-9对胰腺癌的诊断敏感度(78.2%)高于AFP和CEA(P<0.05).对于肝癌、胃癌、胰腺癌和结直肠癌,3项联合检测的敏感度均高于单项检测(P<0.05).结论 血清AFP、CEA和CA19-9联合检测对消化系统恶性肿瘤的早期诊断具有重要意义,可提高诊断的敏感度,且不会降低特异度.     

Application of Joint Detection of AFP,CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identificationand diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and jointdetection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEAin CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s.The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly,and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combinedAFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99).Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity,the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEAare highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosisof CC.     

Establishment of an enzyme immunoassay using monoclonal antibody (HG1-219) and its application for the diagnosis of hepatocellular carcinoma.

A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 +/- 14.5 U/ml measured by EIA-219. When the mean +3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1-219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19-9 suggest that the epitope of HG1-219 Ag is a suger chain similar to CA 19-9.     

乙型肝炎病毒感染与肝细胞癌发生的关系

目的：探讨乙型肝炎病毒（HBV）的可能致癌机理，方法：采用免疫组化和原位分子杂交方法，对慢性乙型肝炎，肝硬化，癌旁肝硬化，肝细胞癌和正常肝组织中的乙型肝炎表面抗原（HBsAg)，核心抗原（HBcAg),HBV,DNA和甲胎蛋白（AFP）水平进行检测。结果：HBsAg,HBcAg和HBV DNA的阳性率在慢性乙型肝炎组中分别为61．9％（13／21），42．9％（9／21），75．0％（12／16），在肝硬化组中分别为64．0％（16／25），36．0（9／25），83．3％（15／18），在癌旁肝硬化组中分别为72．7％（16／22），61．1％（11／18），85．7％（12／14），在肝细胞癌组中分别为45．2％（14／31），50．0％（14／28），64．3％（9／14），慢性乙型肝炎，肝硬化和癌旁肝硬化组中HBV DNA阳性信号较肝细胞癌多而,AFP主在癌旁肝硬化（33．3％，9／27）和肝细胞癌（43．6％，17／39）组中表达，而在慢性肝炎和肝硬化组中不表达，癌旁肝硬化与不伴肝癌的肝硬化有非常显著性差异（P＜0．01），结论：大多数肝细胞癌的发生与HBV感染所致的慢性乙型肝炎和肝硬化密切相关，癌旁肝硬化可能是癌前肝硬化在癌周的残留。     

Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II

PurposeAssessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II).Patients and methodsThe subjects were 16 patients who underwent SBRT for solitary HCC ≤ 3 cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8–43 (median: 28) months, ages from 59–85 (median: 65) years.ResultsChanges in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself.ConclusionsThis is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.     

Establishment of an Enzyme Immunoassay Using Monoclonal Antibody (HG1-219) and Its Application for the Diagnosis of Hepatocellular Carcinoma

A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 ± 14.5 U/ml measured by EIA-219. When the mean + 3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1–219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19–9 suggest that the epitope of HG1–219 Ag is a suger chain similar to CA 19–9.     

肝癌免疫组化诊断谱的研究和应用

目的：探讨鉴别肝细胞癌（HCC）、肝内胆管癌（ICC）和肝转移性腺癌（MAC）的免疫组化诊断谱特点。方法：对手术切除的300例HCC、35例ICC和30例MAC分别进行AFP、Hep Pau 1、CK18、CK19、CA19－9、CD34和pCEA等7种免疫组化染色,将特异性和敏感性的综合性能计分（CCS）≥8分的抗体定为具有高度诊断价值。结果：CCS≥8分的抗体在HCC中为Hep Par 1和CD34,在ICC中为CK19,在MAC中无。Hep Par 1的CCS（9分）明显高于AFP（7分）,其对HCC的敏感性达到83.7%,特异性达到96．7％。结论：HCC的一线抗体由Hep Par 1和CD34组成,二线抗体由pCEA和AFP组成：ICC的一线抗体为CK19,二线抗体为CA19－9。由3种一线抗体组合成肝癌的核心免疫组化谱,酌情使用二线抗体,可以较好地解决对HCC、ICC和MAC之间的免疫病理诊断和鉴别诊断。     

多项肿瘤标志物联合应用对肝癌的诊断价值

目的 探讨甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)、癌胚抗原(CEA)和糖链抗原19-9(CA19-9)四种肿瘤标志物对肝癌的诊断价值.方法 收集70例肝癌患者(肝癌组)、80例慢性肝病患者(慢性肝病组)和80例健康体检者(对照组)的临床资料,比较3组研究对象的血清AFP、AFU、CEA和CA19-9水平及其阳性率,比较原发性肝癌与转移性肝癌患者的血清AFP、AFU、CEA和CA19-9水平,分析多指标联合应用对乙肝表面抗原(HB-sAg)(+)肝癌与HBsAg(-)肝癌患者的诊断价值.结果 肝癌组患者的血清AFP、AFU、CEA、CA19-9水平及阳性率均高于对照组和慢性肝病组(P﹤0.05).原发性肝癌患者的血清AFP和AFU水平明显高于转移性肝癌患者(P﹤0.01),血清CEA水平明显低于转移性肝癌患者(P﹤0.01).不同的筛查组合对HBsAg(+)肝癌患者的诊断灵敏度均高于HBsAg(-)肝癌患者,其中AFP+AFU+CEA筛查对HBsAg(+)肝癌患者的灵敏度和约登指数最高,分别为91.11%和0.80.结论 应用AFP+AFU+CEA进行肝癌筛查的诊断效率较好,适合作为HBsAg(+)肝癌高危人群的筛查项目,且有助于区别原发性肝癌和转移性肝癌.     

Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma

BACKGROUND: Although alpha-fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it has been reported insufficiently sensitive in detecting small HCCs. Plasma transforming growth factor-beta1 (TGFbeta1) has been reported to be elevated in HCC patients compared with liver cirrhosis patients. It has been reported that TGFbeta1 mRNA was overexpressed in HCC, especially in patients with small HCC and well-differentiated HCC compared with patients with liver cirrhosis. The current study investigated the usefulness of TGFbeta1 compared with AFP in the diagnosis of small HCCs. METHODS: Thirty-eight patients with small HCC (< or = 3 cm), 31 patients with liver cirrhosis only, and 23 normal volunteers were studied. Using plasma TGFbeta1 and serum AFP levels measured at the time of diagnosis, the sensitivities and specificities were calculated in the diagnosis of small HCCs. RESULTS: Plasma TGFbeta1 and serum AFP levels were significantly higher in patients with small HCC than in those with liver cirrhosis. In diagnosing small HCCs, the cut-off values of plasma TGFbeta1 and serum AFP were 800 pg/mL and 200 ng/mL, respectively, where the specificities were over 95%. At the cut-off level of plasma TGFbeta1 and serum AFP, the sensitivities were 68% and 24%, respectively. CONCLUSIONS: The current results suggest that TGFbeta1 may be a useful serologic marker in detecting HCCs earlier because it shows higher sensitivity than, with specificity as, AFP in the diagnosis of small HCCs.     

Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: a comparison with CA 19-9 and CEA.

EDAcFN enzyme immunoassay (EIA) is a new tumour marker assay measuring the extra domain A-containing isoform of cellular fibronectin (cFN), a component mainly found in extracellular matrices. The concentration cFN was measured in plasma and serum from 468 patients with malignant and benign diseases. The concentrations of cFN were higher in plasma than in serum. Using receiver operating characteristic (ROC) curve analysis, determination from plasma was superior to serum at specificity levels higher than 78% and was chosen for further analysis. The highest frequencies of elevated cFN values were seen in patients with hepato-pancreato-biliary malignancies (50-67%). In pancreatic and bile duct cancers, cFN provided little further information to that obtained by CA 19-9. The greatest advantage over CA 19-9 and CEA was seen in patients with local colorectal cancer and in hepatocellular carcinomas. Four out of nine patients with Dukes'' stage B colorectal cancer had an elevated cFn level, but only one had an abnormal CEA level. In hepatocellular carcinomas, cFN was also compared with alpha-fetoprotein. The sensitivity of cFN (72%) was superior to that of AFP (61%), and concomitant use of cFN and AFP raised the sensitivity to 83%. The highest frequencies of elevated values in patients with benign diseases were observed in those with severe liver disease (32%) and biliary (17%) and pancreatic (24%) diseases. A combination of cFN and CA 19-9 showed the highest overall sensitivity of 47%, compared with 31% for cFN and 33% for CA 19-9. The corresponding specificities were 76% for cFN +/- CA 19-9, 85% for cFN and 83% for CA 19-9. The accuracy of a combination of cFN and CA 19-9 or CEA (60% respectively) was higher than that of cFN (55%), CA 19-9 (55%) or CEA (45%) alone. In conclusion, the results of the new cFN test are encouraging and further studies on larger patient materials have been started.     

Androgen and estrogen receptors in hepatocellular carcinoma and the surrounding liver in women

Androgen receptors (AR) and estrogen receptors (ER) were consecutively assayed for hepatocellular carcinoma (HCC) and the surrounding liver was removed surgically from 19 female patients. Patient age ranged from 43 to 79 years, with an average of 61 +/- 9 years. All patients had underlying liver disease (liver cirrhosis in 16, liver fibrosis in two, and chronic hepatitis in one). Seven (37%) of 19 HCC had AR ranging from 2.3 to 82.6 fmol/mg of cytosol protein. The AR titer was higher in the HCC than in the liver in these cases. Three cases also had ER. ER existed in seven (37%) tumors (range, 2.4 to 25.6 fmol/mg of protein). AR and ER were detected in 11 (65%) and ten (58%) of 17 nonneoplastic liver tissues, respectively. Serum alpha-fetoprotein (AFP) level, hepatitis B virus markers, or histopathologic types of HCC had no correlation with the presence or absence of AR or ER and their titers. Also, there was no correlation between the AR and ER positivities. Further studies are mandatory to determine the genuine role of sex hormone receptors in the development and growth of HCC in humans.     

The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients

To establish if CA 19-9 could detect early pancreatic cancer, we measured its serum concentration in 866 patients admitted for benign diseases and observed for 2 years. All patients with an elevated CA 19-9 level (greater than 40 units (U)/ml) were submitted to a computed tomography (CT) scan of the pancreas. The CA 19-9 level was increased in 117 patients. One hundred fifteen of these 117 patients had false-positive elevations. The CA 19-9 concentration was elevated mostly in benign hepatobiliary diseases. In this group of patients, CA 19-9 was correlated to alkaline phosphatase values. Eleven patients showed an elevated CA 19-9 level for 10 months without any malignancy developing. One patient had a normal CA 19-9 concentration 8 months before clinical signs of pancreatic carcinoma developed. We conclude that CA 19-9 measurement is of no value for the early detection of this malignancy.     

肝细胞癌与肝炎后肝硬化中多种肿瘤标志物的比较

目的探讨多种肿瘤标志物在肝细胞癌和肝炎后肝硬化中的表达情况。方法采用多种肿瘤标志物蛋白芯片检测系统测定85例肝细胞癌患者和92例肝炎后肝硬化患者血清中肿瘤标志物（CA199、CEA、CA242、FER、AFP、CA125、CA153）的水平,并比较各指标在两组间的差异情况。结果 7项肿瘤指标在肝细胞癌和肝炎后肝硬化中都有不同程度的阳性表达,且CA242和AFP在两组肝病间的比较有明显的统计学意义。结论多种肿瘤标志物的联合检测对肝细胞癌的诊断有较高的临床参考价值,适合于无明显症状的门诊患者的筛查和肿瘤高危人群的普查。     

血清促血管生成素在肝癌中的表达及影响

目的探讨促血管生成素-2（angiogehin-2,Ang-2）对肝细胞肝癌（Hepatocellularcarcinoma,HCC）诊断的临床意义,以期为临床提供有意义的诊断依据。方法采用酶联免疫吸附试验测定30例HCC患者、10例肝硬化患者和10例健康者血清Ang-2水平,同时监测AFP、CEA、CAl99、FERR等肝癌相关指标进行对比。结果HCC组血清Ang-2水平（1892．54±482．82）μg／L和肝硬化组Ang-2水平（1244．21±14．65）μg／L均显著高于健康对照组（943．01±12．52）pg／L（P〈0．01,P〈0．05）,此外HCC组血清Ang-2水平亦显著高于肝硬化组（P〈0．01）。HCC患者血清AFP（4397．61±613．82）μg／L、CA199（64．88±10．71）U／mL、FERR（401．53±51．32）μg／L、CEA（4．69±1．00）μg／L水平显著高于健康对照组（P〈0．01）;其中合并肝硬化组血清Ang-2（2045．41±155．31）μg／L、AFP（5097．17±2830．22）μg／L、CAl99（67．53±9．35）U／mL、FERR（462．87±56．79）μg／L、CEA（5．41±2．25）μg／L水平均高于未发生肝硬化组,差别有统计学意义（P〈0．05,P〈0．01）。结论肝癌患者血清Ang-2增高与HCC的发生、发展有关,血清中Ang-2水平检测可能为HCC临床诊断提供依据。     

The fucosylation index of alpha-fetoprotein and its usefulness in the early diagnosis of hepatocellular carcinoma

The serum concentration and degree of fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples from 258 patients with hepatocellular carcinoma (HCC) and 114 patients with benign liver diseases. When the serum AFP concentration was below 1000 ng/ml, it could not be used as a measure to distinguish between HCC and benign liver diseases. However, the fucosylation index of AFP proved useful for such a purpose. The sensitivity of the analysis using the fucosylation index in total patients with HCC was 69%; the specificity was 96% in benign liver diseases, and the accuracy of this test was 77%. When HCC patients who were grouped according to tumor size (5 cm, 3 cm, and 2 cm in diameter) were analyzed, they all had a fucosylation index significantly higher than that in benign liver disease patients. The mean fucosylation index in 28 patients with a serum AFP concentration below 1000 ng/ml and a tumor diameter less than 3 cm was 26 +/- 30%. Corresponding values for 16 patients with an AFP concentration below 400 ng/ml and a tumor size less than 3 cm and for 8 patients with a concentration below 400 ng/ml and a tumor size less than 2 cm were 32 +/- 31% and 27 +/- 27%, respectively. These values were higher, with statistical significance, than those in patients with benign liver diseases. These data indicate that the measurement of the fucosylation index of AFP is useful for the early diagnosis of HCC.     

Human liver carboxylesterase 1 outperforms alpha‐fetoprotein as biomarker to discriminate hepatocellular carcinoma from other liver diseases in Korean patients

Although alpha‐fetoprotein (AFP) is currently the major serologic biomarker for hepatocellular carcinoma (HCC), it cannot efficiently distinguish this cancer from other forms of liver disease in early diagnosis due to its low sensitivity. The aim of this study is to compare sensitivity and specificity of human carboxylesterase 1 (hCE1) and AFP biomarker. Antibody‐based assays for hCE1 and AFP were used to test both biomarkers with respect to diagnostic efficiency, Youden's index and the area under the curve (AUC) through receiver operating characteristic (ROC) analysis in plasma from 208 patients with HCC (n=57), liver cirrhosis (n=27), chronic hepatitis (n=37), cholangiocarcinoma (n=22), gastric cancer (n=31) and pancreatic cancer (n=34), along with 52 healthy donors (HDs). The levels of hCE1 were significantly higher in patients with HCC than HDs and the other diseases (p<0.005), further verified by AUC values and Youden's index. In the set of HCC versus liver cirrhosis the AUC values were 0.744 (AFP), 0.918 (hCE1) and 0.938 (combination of AFP and hCE1), respectively. These results indicate that hCE1 is not only a more potent and specific marker in distinguishing cancer from liver diseases, in particular cirrhosis, but the combination of hCE1 and AFP shows also synergistic potential for greater sensitivity and specificity in early diagnosis. Therefore the antibody‐based hCE1 assay appears to have high diagnostic efficiency for discriminating HCC from other forms of liver disease. It is now feasible to further validate this novel plasma‐based biomarker in the large cohort we assembled.     

Diagnostic Performance of Circulating Tumor Cells for Predicting of Hepatocellular Carcinoma in Hepatitis C Virus-High Risk Patients: Role of Liquid Biopsy

Purpose: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of HCC. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), albumin, platelets count, and α-fetoprotein were assayed in HCC patients (42), liver cirrhosis patients (83) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-CTCs = AFP (U/L) × 0.08 - Albumin (g/dl) × 84 + CK 18 % × 2.9 + CK19 × 3.1- Platelets count (×109)/L× 0.75– 510. HCC-CTCs score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0. Conclusions: HCC-CTCs score could replace AFP during screening of HCV patients and early detection of HCC.     

原发性肝癌患者肿瘤组织生长抑素受体表达与血AFP水平的相关性

背景与目的:生长抑素类似物(somatostatin analogue,SSTA)对部分原发性肝癌(hepatocellular carcinoma,HCC)患者具有一定疗效,但HCC患者肿瘤组织中生长抑素受体(somatostatin receptor,SSTR)表达状况不详,其与血甲胎蛋白(alphafetoprotein,AFP)的相关性也未见探讨.本研究拟了解肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5亚型的表达状况及其与血AFP的相关性.方法:逆转录-聚合酶链反应及免疫组织化学法分别检测人肝癌及肝硬化组织(各40例)SSTR1、SSTR2、SSTR3、SSTR4及SSTR5亚型的mRNA及蛋白表达:酶联免疫吸附试验检测HCC患者肿瘤组织及外周血AFP水平.结果:肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5蛋白阳性率(分别为47.5%、70.0%、50.0%、65.0%及67.5%)显著高于肝硬化组织(分别为55.0%、67.5%、52.5%、60.0%及47.5%).肝癌组织中SSTR1、SSTR2、SSTR3、SSTR4及SSTR5表达与患者血AFP水平呈二次曲线正相关(r依次为0.882、0.901、0.877、0.854、0.903,P＜0.05).血AFP水平在200～800 μg/L范围时,伴有肝癌组织SSTRs的高表达,过低或过高的血AFP水平伴有SSTR低表达.结论:约60%HCC患者的肿瘤组织表达了SSTRs,其表达量明显高于肝硬化组织;15 AFP水平在200-800μg/L的HCC患者伴有肝癌组织SSTRs的高表达,提示为SSTA治疗的适宜候选者.