Benign Disease Group Research Articles

Clinical value of combined detection of serum CEA, CA199, CA125 in the diagnosis of lung cancer

Objective To investigate the diagnostic value of combined detection of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 125 (CA125) in lung cancer. Methods From July 2017 to February 2019, 64 patients with lung cancer, 40 cases of benign pulmonary lesions and 40 healthy people were selected by random lottery in Fuyang Hospital Affiliated to Anhui Medical University.Serum CEA, CA199 and CA125 levels of each group were analyzed. Results The levels of serum CEA, CA199 and CA125 in patients with lung cancer were significantly higher than those in patients with benign lung disease, the differences were statistically significant (t=18.355, P<0.001; t=11.757, P<0.001; t=10.754, P<0.001). The serum CA125 of lung benign disease group was significantly higher than the healthy group, and the difference was statistically significant(t=6.942, P<0.001). The positive rates of serum CEA, CA199 and CA125 in patients with lung cancer were significantly higher than those in the benign lung disease group and healthy group, the differences were statistically significant(χ2=22.110, P<0.001; χ2=13.321, P=0.002; χ2=15.125, P=0.001). The serum levels of CEA, CA199, and CA125 in patients with middle and advanced stage were significantly higher than those in the early stage, the differences between the advanced group and the early group were statistically significant (t=5.587, P<0.001; t=5.068, P<0.001; t=8.962, P<0.001). Those between the mid-term group and the early group had statistically significant differences (t=4.44, P<0.001; t=4.716, P<0.001; t=12.700, P<0.001). The CEA level of patients with advanced lung cancer was significantly higher than that of the intermediate patients.There was statistically significant difference in the CEA level between the advanced group and the mid-term group (t=3.860, P=0.001). Serum CA125 was the most sensitive in the diagnosis of lung cancer (60.84%), but had the lowest specificity (65.17%). CA125 compared with CA199, CEA, the difference was statistically significant (sensitivity: χ2=10.723, P<0.001 specificity: χ2=4.203, P=0.023). The sensitivity of CEA+ CA199+ CA125 combined detection was significantly higher than single detection, the difference was statistically significant(χ2=26.047, P<0.001), Conclusion The combined detection of serum CEA, CA125 and CA199 has high sensitivity in the diagnosis of lung cancer, which can improve the detection rate of early lung cancer and is worthy of clinical application. Key words: Lung neoplasms; Carcinoembryonic antigen; Antigens, tumor-associated, carbohydrate; Tumor markers, biological; Sensitivity; Specificity

Protein Induced by Vitamin K Absence II (PIVKA-II) as a potential serological biomarker in pancreatic cancer: a pilot study.

IntroductionProtein induced by vitamin K absence II (PIVKA-II) is an abnormal prothrombin increased in gastrointestinal malignancy. We aimed to evaluate PIVKA-II in comparison to established pancreatic cancer (PC) biomarkers (CA 19-9, carcinoembryonic antigen (CEA) and CA 242) measured in PC patients and in patients with benign pancreatic diseases.Materials and methodsWe studied 26 PC patients (Group 1) and 20 patients with benign pancreatic diseases (Group 2). PIVKA-II and CEA were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Gent, Belgium), CA 19-9 and CA 242 were measured by ELSA (CisBio Bioassays, Codolet, France) and EIA (Fujirebio Diagnostics AB, Göteborg, Sweden), respectively. Receiver operating characteristic (ROC) analysis was performed to assess biomarkers’ diagnostic characteristics in both groups.ResultsMedian and interquartile range (IQR) in Group 1 and Group 2 were: 1749.0 (320.2 – 3921.0) vs. 31.0 (23.0 – 43.0) mAU/mL (P < 0.001) for PIVKA-II, 260.0 (158.7 – 272.0) vs. 45.2 (9.0 – 58.0) U/mL (P = 0.034) for CA 19-9, 104.0 (30.2 – 150.0) vs. 7.2 (4.8 – 26.0) U/mL (P < 0.050) for CA 242, 9.4 (5.3 – 37.5) vs. 4.5 (1.8 – 7.0) ng/mL (P = 0.021) for CEA. Areas under the ROC curve of PIVKA-II, CA 19-9, CA 242, CEA were 0.86 (95% CI: 0.71 – 1.00), 0.58 (95% CI: 0.38 – 0.78), 0.73 (95% CI: 0.54 – 0.92), 0.64 (95% CI: 0.44 – 0.85), respectively.ConclusionsPIVKA-II is significantly higher in PC than in benign pancreatic diseases. PIVKA-II shows a rather good diagnostic performance compared to CA 19-9, CEA and CA242, thus its determination could help PC management.

Associated measurement of fucosylated levels of AFP, DCP, and GPC3 for early diagnosis in hepatocellular carcinoma.

Hepatocellular carcinoma is a serious health problem worldwide, especially in Asian countries, such as China. However, there are difficulties in diagnosing and treating hepatocellular carcinoma. The alteration of fucosylated proteins was closely associated with carcinogenesis. This study is designed to evaluate the early diagnostic value of associated detection of fucosylated alpha-fetoprotein (fuc-AFP), fucosylated des-γ-carboxy prothrombin (fuc-DCP), and fucosylated glypican 3 (fuc-GPC3) in hepatocellular carcinoma. All serum specimens collected from patients were diagnosed by complete clinicopathological examination and then subjected to the associated detection of fuc-AFP, fuc-DCP, and fuc-GPC3 by protein microarray. Canonical discriminant analysis was adopted to discriminate between the hepatocellular carcinoma group and the benign liver disease group. A total of 51 patients with hepatocellular carcinoma and 47 patients in the benign liver disease group were included in this study. Fuc-AFP, fuc-DCP, and fuc-GPC3 were significantly higher in the hepatocellular carcinoma group than in the benign liver disease group. The sensitivity, specificity, and accuracy of canonical discriminant analysis classification were 80.4%, 97.9%, and 88.8%, respectively. Fuc-AFP, fuc-DCP, and fuc-GPC3 are effective and useful tumor biomarkers. Associated measurement of these biomarkers with canonical discriminant analysis classification is a promising method for the early diagnosis of hepatocellular carcinoma.

Background and precancerous processes in the vulva and vagina: etiology, pathogenesis, diagnosis and treatment

Leukoplakia, kraurosis and pointed condylomas (papillomas) of the vulva represent the group of background benign vulvar diseases. Vulvar and vaginal intraepithelial neoplasms are classified as premalignant conditions. The etiology and pathogenesis of these diseases are not entirely clear due to their complexity. Despite the easy visual assessment of anatomic areas involved in the pathological process, these diseases are rarely diagnosed at an early stage, which might indicate insufficient vigilance of doctors and patients in relation to the early symptoms. Therefore, this field of oncogynecology needs further development ln terms of diagnosisprevention, screening and treatment.

Clinical significance of recombinant virus-specific detection for viable circulating tumor cells in lung cancer patients

Objective: To investigate the clinical significance of recombinant virus-specific detection for detecting viable circulating tumor cell (CTC) in lung cancer patients. Methods: From June 2017 to August 2018, 63 lung cancer patients diagnosed by imaging and pathology at the Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital were recruited for this study, including 38 cases of adenocarcinoma, 13 squamous cell carcinoma, and 12 small cell carcinoma. The patients consisted of 36 males and 27 females, with an average age of (65±11) years. In addition,21 patients with benign lung diseases were recruited for benign lung disease group, including 11 males and 10 females with an average age of (57±13) years. Another 18 healthy subjects were recruited for the healthy control group, including 10 males and 8 females, with an average age of (32±10) years. The peripheral blood viable CTCs were detected by a CTC in vitro detection kit containing recombinant virus. Fisher's exact test was used to compare the differences between the groups of viable CTC positive rates. Results: Cases with positive viable CTC in the lung cancer group, the benign lung disease group and the healthy control group were 56,4 and 0, respectively. The sensitivity and specificity of this CTC detection system were 89% (56/63) and 90% (35/39) , respectively. The positive rate of CTC detection for lung cancer patients with adenocarcinoma, aquamous cell carcinoma, and small cell carcinoma, were 84%(32/38), 92% (12/13) and 100% (12/12), respectively. The positive cases from adenocarcinoma and squamous cell carcinoma patients with different stages were 2 (n=2) in stageⅠ,6 (n=8) in stage Ⅱ,7(n=8) in stage Ⅲ and 29(n=33) in stage Ⅳ. There were no significant differences in the positive rates of CTC among different histological types or different stages (χ(2)=1.881, 3.419; P>0.05) . Conclusion: This CTC detection system was found to be a simple and non-invasive method for auxiliary diagnosis of lung cancer, with high sensitivity and specificity.

Comment on "Research on values of GDF-15 level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect".

Objective To investigate the values of growth differentiation factor-15 (GDF-15) level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect. Patients and methods 92 patients with liver cancer treated from June 2015 to May 2016 were selected as liver cancer group; 53 patients with benign liver lesion were selected as benign liver disease group, and 40 healthy subjects receiving physical examination were selected as healthy control group. Fasting venous blood was drawn from objects of study in the early morning at 1 d after admission and at the last day after chemotherapy (liver cancer group), and the serum GDF-15 level was measured. Results The serum GDF-15 levels in patients in liver cancer group and benign liver disease group were significantly higher than those in healthy control group and benign liver disease group (p 0.05). The ROC curve analysis showed that the threshold value of GDF-15 was 1573.23 ng/L, and the sensitivity, specificity, and accuracy were 81.23%, 83.99%, and 83.62%, respectively. The serum GDF-15 level in patients with progressive disease was significantly higher than those in patients with partial remission and stable disease, and the serum GDF-15 level in patients with stable disease was significantly higher than that in patients with partial remission (p Conclusions The serum GDF-15 level has certain clinical values in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect.

Vascular Endothelial Growth Factor-D (VEGF-D) is Elevated in Bronchoalveolar Lavage Fluid of Patients with Lung Squamous Carcinoma.

Previous studies have found that vascular endothelial growth factor (VEGF) is associated with lung cancer, yet little is known about vascular endothelial growth factor-D (VEGF-D) in bronchoalveolar lavage fluid (BALF) of lung cancer patients. In this study, we aim to investigate the expression and evaluation of VEGF-D in BALF for lung cancer diagnosis. BALF samples were acquired from 81 patients: 40 with benign diseases and 41 with lung cancer. The expression of VEGF-D in BALF was measured using sandwich enzyme-linked immune sorbent assays (ELISA), and the evaluation of VEGF-D in BALF for lung cancer diagnosis was also investigated. In the BALF samples, the levels of VEGF-D in the lung cancer group were higher than in the benign disease group; however, there was no statistical significance between the two groups (p > 0.05). In the pathological classification of lung cancer, the levels of VEGF-D in the BALF differed significantly between the lung squamous carcinoma group and the benign disease group (p < 0.05). The diagnostic accuracies of VEGF-D in BALF for discrimination between patients with squamous cell carcinoma and benign disease were reasonable based on receiver operating characteristic (ROC curve) analysis, with a corresponding sensitivity of 64.7% and specificity of 60%, respectively. This study demonstrated that the detection of VEGF-D levels in BALF is a valuable diagnostic tool for lung squamous carcinoma.

Value of the concentration and integrity of serum cell-free DNA for the clinical diagnosis of esophageal carcinoma

Objective: To explore the diagnostic value of serum cell-free DNA (cfDNA) concentration and integrity for esophageal carcinoma. Methods: Venous blood samples from 68 patients with esophageal cancer, 36 patients with benign esophageal lesions and 45 healthy subjects were collected. Circulating cfDNA was verified through quantitative real-time PCR (Alu-qPCR) using Alu-115 and Alu-247 primers. DNA integrity index was calculated as the ratio of Alu-qPCR results (Alu247/115). Concentrations of carcino-embryonic antigen (CEA) and squamous cell carcinoma associated antigen (SCC) were detected by chemiluminescence analyzer assay. Statistical analysis was performed using Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlation test. The Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of each index to esophageal carcinoma. Results: The median absolute serum Alu115 and the Alu247/115 index (1 162.0 ng/ml, 0.57) in esophageal cancer group were significantly higher than those in benign esophageal disease group (496.7 ng/ml, 0.43) and in healthy control group (432.3 ng/ml, 0.42) (all P<0.01, respectively). The Alu115 and Alu247/115 index of serum DNA in benign esophageal disease group were no statistically different from those in the healthy control group (all P>0.05, respectively). The levels of cfDNA and its integrity were not significantly correlated with age, gender, tumor differentiation, or disease stage according to American Joint Committee on Cancer (AJCC) staging system in the esophageal cancer group (all P>0.05). The serum Alu247/115 index of Stage Ⅲ patients was higher than that of Stage Ⅰ~Ⅱ patients(P<0.05). The serum Alu247/115 index of Stage Ⅳ was higher than that of Stage Ⅲ(P<0.05). In the esophageal cancer group, both of serum Alu115 and Alu247/115 index had no correlation with CEA or SCC (all P>0.05). The area under the ROC curve (AUC) of Alu115 and Alu247/115 index were 0.867 and 0.854, respectively, which were both higher than that of CEA (0.622) and SCC (0.753). The addition of Alu115 or Alu247/115 index to CEA and SCC detection increased the sensitivity of the diagnosis of esophageal cancer by 95.6% and 94.1%, respectively. Conclusions: The detection of serum cfDNA concentration and integrity is helpful to the early diagnosis and monitoring of esophageal cancer. Their diagnostic value of esophageal cancer is better than that of the traditional tumor markers CEA and SCC.

Diagnostic value of serum human epididymis protein 4 and carbohydrate antigen 125 combined with risk of ovarian malignancy algorithm index for ovarian cancer

Objective To investigate the clinical value of serum human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) combined with risk of ovarian malignancy algorithm (ROMA) index in the diagnosis of ovarian cancer. Methods A total of 541 patients in the Department of Gynaecology in Baoji Central Hospital from August 2016 to February 2018 were collected. The serum HE4 and CA125 levels were measured by using electrochemiluminescence immunoassay in 226 cases of ovarian cancer (ovarian cancer group), 315 cases of ovarian benign disease (ovarian benign disease group) and 100 female healthy people (the control group). ROMA index was calculated according to ROMA model and the results were analyzed statistically. Results The levels of serum HE4, CA125 and ROMA index were significantly different in premenopausal and postmenopausal ovarian cancer group, ovarian benign disease group and the control group (all P < 0.05). The sensitivity and Yonden's index of the three combined diagnosis of serum HE4, CA125 and ROMA for premenopausal ovarian cancer were 97.01% and 77.01% respectively, which were higher than those of a single detection (HE4: 79.37%, 69.11%; CA125: 76.06%, 66.38%; ROMA index: 89.55%, 72.41%; χ2sensitivity=12.35, P=0.000; χ2Yonden's index=6.460, P=0.013. The sensitivity and Yonden's index of the three combined diagnosis of serum HE4, CA125 and ROMA for postmenopausal ovarian cancer were 98.99% and 82.99% respectively, which were higher than those of a single detection (HE4: 86.90%, 79.40%; CA125: 82.98%, 76.31%; ROMA index: 93.54%, 80.64%; χ2sensitivity=14.25, P=0.000; χ2Yonden's index=4.822, P=0.031). The area under the curve of the combined detection of three indicators was higher than that of a single detection (premenopausal group: 0.871 vs. 0.682, 0.626, 0.708; postmenopausal group: 0.981 vs. 0.724, 0.705, 0.833), and there were significant differences (premenopausal group: χ2= 11.24, P= 0.000; postmenopausal group: χ2= 16.38, P= 0.000). Conclusion The combined detection of serum HE4, CA125 and ROMA index can increase the sensitivity and accuracy for diagnosing ovarian cancer, which can provide a more reliable basis for diagnosis and screening of ovarian cancer. Key words: Ovarian neoplasms; Human epididymis protein 4; Carbohydrate antigen 125; Risk of ovarian malignancy algorithm; Diagnosis

Where to "cut-off"?

Where to "cut-off"?

P2.11-07 Lung Cancer in a Tertiary Care Setting: So Near, Yet So Far

Lung cancer patients usually present in advanced stage. Once diagnosed, these patients do not take treatment/tend to leave it in-between, because of various financial and psychosocial problems, and issues related to administration of chemotherapy and side effect profile. If diagnosed at an early stage, lung cancer has a high overall 5 year survival. In developing countries, with a high burden of lung cancer and its associated morbidity and mortality, there is a need to screen the ‘at risk’ population, thus facilitating early diagnosis. Lung cancer patients were hence studied at presentation and followed up to 10-12 weeks after diagnosis. The utility of a biomarker, Heat shock protein 90-beta (Hsp 90-beta) was assessed along with. 60 individuals were included: 20 histologically/cytologically proven patients of lung cancer before treatment initiation(Group A), 20 patients with benign lung diseases(Group B) and 20 apparently healthy individuals(Group C). After thorough investigations and staging (TNM classification), patients of Group A were administered chemotherapy (NCCN guidelines), and followed up to 10-12 weeks after diagnosis. Also, 5ml of venous blood was collected from all individuals for Hsp90-beta evaluation by ELISA. In Group A, 1/20 patient was diagnosed with stage 3, rest 19/20 patients were diagnosed with stage 4 lung cancer. Predominant histopathological type was squamous cell carcinoma (14/20 patients), followed by adenocarcinoma (4/20) and small cell carcinoma (2/20). At follow up, 35% (7/20) patients were dead/lost to follow up. 13 patients were given chemotherapy, 10/13had partial response and 3/13 had progressive disease (RECIST Criteria). The 3groups were age and gender matched. Mean serum Hsp90-beta levels were 242.850, 129.825 and 107.150ng/ml in group A,B and C respectively. Group A had significantly higher levels (p<0.0005, cut off value: 146.5ng/ml, 95%sensitivity and specificity). The levels did not differ with histological type/stage of cancer. At follow up, in 13 patients of Group A, mean Hsp90-beta levels showed an increase. Majority of the patients presented in stage 4 signifying the urgent need of a diagnostic/screening tool for detection in early stages. Also, various factors which could be responsible for a high attrition rate due to death/lost to follow up need to be studied, so that specific interventions can be planned. Serum Hsp90-beta could be a valuable biomarker in diagnosis/screening of lung cancer. However, its prognostic role needs elucidation. Detailed studies with larger sample size, different histologies and different stages are required to establish various strategies for early diagnosis and timely comprehensive management, so as to drive the final treatment outcomes in a positive direction.

Clinical application value of soluble co-stimulatory molecule B7-H1 detection in colorectal cancer

Objective To determine the level of soluble B7-H1 (sB7-H1) in serum of patients with colorectal cancer (CRC), and to investigate its clinical application value in CRC. Methods 152 cases of CRC, 57 cases of benign colorectal diseases and 59 healthy subjects were enrolled. ELISA was used to determine the sB7-H1 level in serum. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 72-4 (CA72-4) were determined by electrochemiluminescence. The level of carbohydrate antigen 50 (CA-50) was determined by chemiluminescence. ROC curve was used to evaluate the diagnostic efficiency of sB7-H1 alone or combined with other tumor markers in CRC.It also analyzed the correlation between serum sB7-H1 level and some clinicopathological characteristics including tumor location, depth of invasion, lymph node metastasis status, distant metastasis status and tumor stages. Results (1)The differences of sB7-H1 level among CRC group, colorectal benign disease group and healthy control group (compared with each other respectively) were statistically significant (P 0.05). (2)The diagnosis ability of sB7-H1, CEA, CA19-9, CA72-4, and CA-50 were determined by the area under curve (AUC), which was 0.730, 0.772, 0.639, 0.663 and 0.635, respectively. The combination of sB7-H1 and CEA showed the best effect, and the AUC reached 0.831. (3)There was no significant correlation between the levels of sB7-H1 and CEA, or CA19-9, CA72-4, CA-50. (4)Immunohistochemistry result showed that the positive rate of CRC group was 52%, while that of benign disease group was 6.3%. The difference of the positive rate between two groups was statistically significant (P 0.05). Conclusion Serum sB7-H1 has a high clinical application value and could serve as a new tumor marker in CRC.(Chin J Lab Med, 2018, 41: 669-674) Key words: Colorectal neoplasms; Antigens, CD274; Biomarkers, tumor

Association of CYP19A1 gene rs7176005 single nucleotide polymorphism with breast cancer risk and clinicopathologic features of tumor

Objective: The aim of this study was to investigate the association of the CYP19A1 rs7176005 single nucleotide polymorphism (SNP) with breast cancer risk and with clinicopathologic features of tumors. Methods: This study was conducted by including 138 patients with breast cancer (cancer group), those who diagnosed as primary breast cancer after operation by pathology. There were 293 cases in the group of benign breast disease which was presented as a solid mass by the color ultrasound and pathologically diagnosed as "fibroadenoma or adenosis" (benign breast disease group), the cases were paired with breast cancer patients by age±5 in the same period, and there were 259 cases in the group of healthy control who received routine physical examination during the same period and were paired with breast cancer patients by age±5 without any detection of breast related diseases (healthy control group) at West China hospital between September 2012 and November 2016. The CYP19A1 rs7176005 SNP was detected by a direct sequencing method. Hardy-Weinberg test was used to analyze the genetic balance of the 3 groups. Chi square test was used to compare the distribution of rs7176005 genotypes between the 3 groups, and the differences of clinicopathological features in breast cancer patients carrying different genotypes. Results: The ages of the breast cancer cases, the benign breast disease group and the healthy control group were (44.69±8.09), (42.33±11.44) and (41.92±9.61) years old, respectively. Hardy-Weinberg equilibrium test identified that the composition ratios of alleles C and T in breast cancer group, benign breast disease group and healthy group were not statistically significant (χ(2) values were 0.83, 0.34 and 0.04, respectively, P values were 0.363, 0.561, and 0.852, respectively). All the three groups met the genetic balance, had consistency and could represent the population. Among the 138 cases of breast cancer, the CYP19A1 rs7176005 SNP was significantly associated with the diameter of the tumor (P=0.031). The majority of tumor size was <2 cm in patients who carrying TT and CT genotypes, and the proportion was 75% (12/16) and 58% (40/69), respectively. While those patients with TT genotype were mainly >2 cm and ≤5 cm, and the proportion was 51% (27/53). The distribution of TNM stage among patients with different genotypes was also statistically significant (χ(2)=11.19, P=0.025). The most common stage was Ⅱ in Patients who carrying CC and CT genotypes, and the proportion was 45.3% (24/53) and 52.2% (36/69), respectively. While those patients with TT genotype was mainly in stage Ⅰ and the proportion was 56.3% (9/16). Conclusion: Though the CYP19A1 rs7176005 SNP is not associated with breast cancer development, breast cancer patients with the C allele exhibit a high tumor growth rate and large diameters.

The value of ENO1 autoantibodies and CEA combination in the diagnosis of lung adenocarcinoma

Objective To study the differential diagnostic efficacy of α-enolase (ENO1) autoantibodies in lung adenocarcinoma, benign pulmonary disease, and normal individuals, and to evaluate the improvement of the diagnostic efficiency of existing markers by establishing a binary logistic regression model. Methods This was a case-control study. Participants were from the public health welfare program led by the National Cancer Center/Chinese Academy of Medical Sciences Peking Union Medical College Cancer Hospital. Serum samples were collected June 2014 to June 2017 including 60 patients with lung adenocarcinoma, 50 patients with benign lung diseases, and 90 healthy controls. Luminex MAGPIX platform was applied to detect serum ENO1 autoantibodies, CEA and Cyfra21-1 proteins. The receiver operating characteristic curve (ROC)analysis and binary logistic regression were used to evaluate the performance and build diagnostic model. Results The median level of serum ENO1 autoantibody in patients with lung adenocarcinoma was 918.5(665.5-2 043.3), which was significantly higher than that in the normal individuals (722.5, 585.5-921.8, Z=-3.113, P=0.002) and benign lung disease patients (693.0, 501.4-973.3, Z=-3.395, P=0.001). And no significant differences between benign disease groups and normal individuals (Z=-1.155, P=0.248). ROC was plotted, and the area under the curve (AUC) of ENO1 autoantibodies was 0.664 (95% confidence interval: 0.576-0.752), while the AUCs of existing diagnostic marker CEA and Cyfra21-1 were 0.680 (95% confidence interval: 0.594-0.767) and 0.617 (95% confidence interval: 0.532-0.703). A joint diagnostic model including ENO1 and CEA was built with an AUC of 0.757 (95% confidence interval: 0.675-0.838). The diagnostic efficacy of the model was significantly different from ENO1 autoantibodies (Z=2.648, P=0.008). When the specificity was 90%, the sensitivity of ENO1 autoantibodies was 38.3%, while the sensitivity of the combination with CEA was raised to 50%. Conclusion ENO1 autoantibodies could be a marker for the auxiliary diagnosis of lung adenocarcinoma, and can improve the efficacy of the existing diagnostic markers such as CEA. ENO1 has the potential use for the diagnosis and screening.(Chin J Lab Med, 2018, 41: 446-449) Key words: Lung adenocarcinoma; Alpha-enolase; Diagnosis

Research on values of GDF-15 level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect.

To investigate the values of growth differentiation factor-15 (GDF-15) level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect. 92 patients with liver cancer treated from June 2015 to May 2016 were selected as liver cancer group; 53 patients with benign liver lesion were selected as benign liver disease group, and 40 healthy subjects receiving physical examination were selected as healthy control group. Fasting venous blood was drawn from objects of study in the early morning at 1 d after admission and at the last day after chemotherapy (liver cancer group), and the serum GDF-15 level was measured. The serum GDF-15 levels in patients in liver cancer group and benign liver disease group were significantly higher than those in healthy control group and benign liver disease group (p<0.05). The serum GDF-15 levels in patients with stage III and IV liver cancer were significantly higher than those in patients with stage I and II liver cancer, and the serum GDF-15 level in patients with stage IV liver cancer was significantly higher than that in patients with stage III liver cancer (p<0.05). There was no significant difference in serum GDF-15 level among patients with different clinical data (p>0.05). The ROC curve analysis showed that the threshold value of GDF-15 was 1573.23 ng/L, and the sensitivity, specificity, and accuracy were 81.23%, 83.99%, and 83.62%, respectively. The serum GDF-15 level in patients with progressive disease was significantly higher than those in patients with partial remission and stable disease, and the serum GDF-15 level in patients with stable disease was significantly higher than that in patients with partial remission (p<0.05). The serum GDF-15 level has certain clinical values in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect.

The clinicopathological significance of Ki67 in papillary thyroid carcinoma: a suitable indicator?

BackgroundTo explore Ki67 expression in papillary thyroid carcinoma (PTC) and its clinical-pathological significance.MethodsA total of 776 consecutive PTC and benign thyroid disease patients underwent thyroidectomy at Shanghai General Hospital from January 2013 to December 2015 and were retrospectively analysed. Ki67 expression was determined in the PTC and benign thyroid disease tissues, and other clinicopathological factors were identified via statistical analyses.ResultsThe Ki67 expression intensity in the PTC group was significantly higher than that in the benign thyroid disease group. In the PTC group, a tumour size ≥ 1 cm and coexistence with thyroiditis were significantly associated with the Ki67 expression intensity. The TGAb and TPOAb plasma levels were linearly correlated with the Ki67 expression intensity. Moreover, the tumour size and Ki67 expression intensity also showed a linear correlation. Receiver operating characteristic (ROC) curve analysis suggested that the optimal cut-off value of Ki67 was 2.50%. Two groups divided by Ki67 cut-off values showed significant differences in the recurrence survival rate.ConclusionsKi67 is a suitable biomarker for distinguishing PTC from benign thyroid disease. Ki67 expression was related to the tumour size, thyroiditis and plasma levels of TGAb and TPOAb in PTC. Ki67 could be used as a prognostic indicator in PTC. Patients with high Ki67 expression are more likely to experience disease recurrence.

Serum receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a diagnostic and prognostic marker for non-small cell lung cancer.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and apoptosis in cells bearing the RCAS1 receptor. The aim of the study was to elucidate the diagnostic and prognostic value of RCAS1 levels in patients with non-small cell lung cancer. Sera collected from 30 healthy volunteers, 40 patients with benign lung diseases and 97 non-small cell lung cancer cases were subjected to RCAS1 ELISA, and relationships between serum RCAS1 and clinical characteristics were evaluated. Serum RCAS1 levels were higher in the non-small cell lung cancer group than in the healthy volunteers and benign lung disease groups (P <0.001). With a cutoff level 19.8 U/ml, RCAS1 had a sensitivity of 87.6%, a specificity of 82.5% and an accuracy of 86.1% for non-small cell lung cancer. Univariate analysis revealed that non-small cell lung cancer patients with elevated RCAS1 levels had significantly shorter overall survival (P = 0.042) than the other two groups. By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (P = 0.003). Assessment of serum RCAS1 levels could be considered as a diagnostic and prognostic marker in non-small cell lung cancer.

Diagnostic usefulness of KL-6 concentration of bile in biliary tract cancer.

The sensitivity of bile cytology for biliary tract cancer varies from 6-64%, and hence remains unsatisfactory. Sialylated carbohydrate antigen KL-6 mucin is positive in biliary tract cancer tissues and serum KL-6 levels are significantly increased in intrahepatic ductal adenocarcinoma patients compared with healthy individuals. The aim of the present study was to evaluate the usefulness of the KL-6 concentration of bile for the diagnosis of biliary tract cancer. Bile cytology and measurements of bile KL-6 concentration were conducted for 43 patients (25 biliary tract cancers and 18 benign biliary disease). The concentration of KL-6 in the bile of the biliary tract cancer group was compared with the benign biliary disease group. The diagnostic ability was assessed by using receiver operating characteristic curves (ROC). The mean KL-6 concentration of bile for biliary tract cancer (34.6±51.6 U/ml) was increased compared with benign biliary disease (5.2±3.9 U/ml, P<0.001). The area under the ROC for diagnosis of biliary tract cancer was 0.84 for benign biliary disease. When the cut-off level of the KL-6 concentration of bile was 8.6 U/ml, the sensitivity, specificity, and accuracy of the KL-6 concentration of bile alone for the diagnosis of biliary tract cancer were 72, 89, and 79%, respectively. Adding the bile KL-6 concentration to bile cytology measurements, the sensitivity for the diagnosis of biliary tract cancer was increased significantly (100%, P=0.0184). The KL-6 concentration of bile may strengthen the sensitivity of bile cytology for biliary tract cancer.

The diagnostic value of five serum tumor markers for patients with cholangiocarcinoma

ObjectiveTo assess the clinical significance and diagnostic value of the single and combined detection of five tumor markers in patients with cholangiocarcinoma. MethodsIn total, 296 patients with biliary tract disease who were diagnosed and received treatment at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (17113011) during April 2011 to Dec 2017 were chosen for this study. Patients were divided into a cholangiocarcinoma group and a benign biliary tract disease group. Serum was collected from the patients, and the concentrations of AFP, CEA, CA125, CA19-9, CA72-4 and total bilirubin (TBIL) were tested. BM SPSS Statistics 22.0 was used to analyze the data. Receiver-operating characteristic (ROC) curves for the single and combined detection of five tumor markers were generated, and the sensitivity, specificity, and area under ROC curve (AUC) were calculated. ResultsThe concentrations of serum tumor markers in the cholangiocarcinoma group were higher than those in the benign biliary tract disease group. The AUCs for the single detections of the AFP, CEA, CA125, CA19-9, CA72-4 were 0.654, 0.808, 0.772, 0.833, and 0.743, and the optimal cutoffs were 2.58 ng/mL, 2.85 ng/mL, 23.85 U/mL, 46.75 U/mL, and 2.46 U/mL respectively. The combined detection of CEA, CA125 and CA19-9 had great diagnostic value. Its AUC was 0.888, its sensitivity was 85.1%, and its specificity was 83.1%. ConclusionsThe levels of CEA, CA125, CA19-9 and CA72-4 had a different diagnostic value for cholangiocarcinoma, and combined serum CEA, CA125 and CA19-9 would have the best clinical diagnostic effect of cholangiocarcinoma.

Clinical value of ALU concentration and integrity index for the early diagnosis of ovarian cancer: A retrospective cohort trial.

CA125 amounts have a large overlap in ovarian cancer and benign diseases. We conducted a retrospective cohort trial to assess the clinical value of circulating cell-free DNA concentration and integrity index for the diagnosis of ovarian cancer. A total of 150 patients were recruited. Plasma samples of 24 ovarian cancer patients, 12 benign ovarian cysts, and 12 healthy controls were assessed. By amplifying short ALU-115 repeat and long ALU-219 fragments, circulating cell-free DNA concentrations and integrity index were measured. Plasma ALU-219 fragment levels and integrity index were significantly higher in the ovarian cancer group compared with the benign disease and healthy control groups (p = 0.023 and p = 0.004, respectively). These findings indicated that plasma ALU-219 levels and integrity may have a clinical value in the early diagnosis of ovarian cancer.