Serum Tumor Biomarkers Research Articles

Serum carbohydrate antigen 125 is a significant prognostic marker in patients with unresectable advanced or recurrent gastric cancer.

We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer. The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients. The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5months, which was significantly shorter than that of a normal range group (18.3months, P<0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P<0.001). Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival.

Opto-Electron Eng, 2017, 44(2)] Research progress in applications of LSPR biosensor for clinical medicine detection

Tumor biomarker plays an important role in early diagnosis, treatment evaluation, and prognosis prediction for human medicine and cancers. At present, the human serum tumor biomarker detection methods mainly include radioimmunoassay (RIA), enzyme linked immunosorbent assay (ELISA), and chemiluminescence immunoassay (CLEIA), which have disadvantages of radioactive contamination, complicated operation, and long detection time and high cost. Various issues exist in these methods which limit its widespread applications in clinic screening. Recently, biosensors based on localized surface plasmon resonance (LSPR) have attracted much research attention for their remarkable superiority in the domain of biomedicine detection. The LSPR biosensor, a novel type of optical fiber-based biosensor, uses an optical fiber or optical fiber bundle to transform biological rec-ognition information into analytically useful signals in the LSPR spectrum, which is suitable for clinical detection because of the advantages of high sensitivity, high specificity, label free, portable equipment and lower cost. However, up to now, there was little progress on the report of the detection of tumor biomarkers associated diseases and tumors by using this LSPR biosensor. In this paper, the principle and research progress of local surface plasmon resonance biosensor, as well as the main findings of our study in the detection of tumor markers are reviewed.

Nomograms for predicting the prognostic value of serological tumor biomarkers in colorectal cancer patients after radical resection

A wide range of serum tumor biomarkers, including CA19-9, CA242, CA72-4, CA50, and CA125, has been studied in association with colorectal cancer (CRC). However, few previous studies have comprehensively considered the above tumor biomarkers to assess their clinical significance in predicting prognosis. Data from Fudan University Shanghai Cancer Center (FUSCC) between January 1, 2007 and December 30, 2012 was retrospectively analyzed. Univariate and multivariate analyses were performed to assess the association between prognostic factors and survival outcomes. Nomograms were established based on multivariate Cox regression model analysis for overall survival (OS) and disease free survival (DFS), and c-indexes were 0.772 (95% CI: 0.724-0.820) and 0.715 (95% CI: 0.678–0.752), respectively. Subgroup analyses according to CEA status (high/normal) suggested that CA724 was the only independent prognostic factor for OS (P = 0.001) and DFS (P < 0.001) in the CEA-high group, while, in the CEA-normal group, the only independent prognostic factor for OS (P = 0.031) and DFS (P = 0.043) was CA50. CA50 and CA724 could supplement CEA in monitoring recurrence and metastasis. Accordingly, nomograms based on CEA, CA50, CA724 and other clinical-pathological factors could improve prognosis prediction for colorectal cancer patients.

التأثير الواقي لعصائر الرمان والفراولة ضد سرطان الکبد الناجم عن نيتروز داى إ يثيل أمين في الفئران Protective Effect of Pomegranate and Strawberry Juices against Hepatocarcinoma Induced by Nitrosodiethylamine in Rats

This study aimed to evaluate the protective effect of pomegranate juice (PJ) and strawberry juice (SJ) against hepatocarcinoma induced by nitrosodiethylamine (NDA) in rats. Forty two male rats were distributed into 6 equal groups. Group 1 was negative control and the other 5 groups were intoxicated by a single intraperioneal dose (60 mg/kg B.wt.) of NDA in the 3rd week of experiment, followed by weekly 3 subcutaneous injections of CCl4 till the end of experiment (8 weeks) to induce hepatocarcinoma. Group 2 was kept positive (intoxicated) control and groups 3, 4, 5 and 6 were orally given PJ and SJ at low (5%) and high (10%) concentrations for 8 weeks, respectively. Changes in serum biochemical parameters, tumor biomarkers and liver histology were used to evaluate the protective effect. Lipid peroxidation, antioxidant defense capacity and content of 8-hydroxy-2-deoxyguanosine (8-OHdG) in liver DNA (a marker of apoptosis) were measured to examine the mechanism of action. Oral administration of PJ and SJ inhibited NDA-induced elevations in serum biochemical aspartate aminotransferase (AST), alanine aminotransferase(ALT), alkaline phosphatase (ALP) and total bilirubin(T Bil) and in tumor biomarkers (alpha fetoprotein, tumor necrosis factor-alpha and nuclear factor-kappa beta) levels. The results showed that oral administration of PJ and SJ ameliorated hepatic preneoplastic lesions induced by NDA, counteracted hepatic lipid peroxidation, alleviated hepatic oxidative stress and antagonized NDA-induced elevation of 8-OHdG content in liver DNA. These findings denoted that PJ and SJ produce a protective effect against hepatocarcinoma induced by NDA. The protective mechanism of action might be due to inhibition of hepatic lipid peroxidation, lowering oxidative stress and induction of apoptosis. استهدف هذا البحث دراسة التأثير الواقي وفحص آليات العمل لعصائر الرمان والفراولة ضد سرطان الکبد الناجم عن نيتروز داى إ يثيل أمين فى الفئران. فتم توزيع عدد 42 من ذکور الفئران البالغة بطريقة عشوائية إلى 6 مجموعات کل منها 7 فئران. المجموعة الأولى کانت ضابطة سالبة (فئران غير مصابة) والمجموعة الثانية ضابطة موجبة (فئران مصابة)، والمجموعات الثالثة والرابعة والخامسة والسادسة کانت فئران مصابة بالسرطان وسبق إعطائها عن طريق الفم عصير الرمان والفراولة وکل منهما بترکيز صغير(5 %) وکبير (10 %) على التوالى لمدة 8 اسابيع. وتم إحداث اﻹصابة بالسرطان بحقن الفئران فى التجويف البريتونى بجرعة مفردة ( 60 مجم/کجم) من نيتروز داى إ يثيل أمين فى الأسبوع الثالث من فترة التجربة وتلى ذلک حقن الفئران تحت الجلد برابع کلوريد الکربون (مخفف مع زيت البرافين بنسبة 1:1) بکمية 2سم/کجم ثلاث حقنات فى الأسبوع أثناء الأسابيع الرابع والخامس والسادس والسابع والثامن. وفى نهاية فترة التجربة تم تجميع عينات من الدم لعمل التحليلات البيوکيميائية فى المصل ، وتم أخذ نصف الأکباد لقياس دلائل أکسدة الدهون ونشاط اﻹنزيمات المضادة للأکسدة (سوبر أوکسيد دثميوتيز - جلوتاثيون بيرأوکسيديز- کاتاليز) وترکيز مرکب 8- هيدروکسى- دى اوکسى جوانوزين (دليل موت الخلايا المبرمج ) فى نسيج الکبد. واستخدم النصف الآخرﻹجراء الفحص الهستوباثولوجى للکبد. وأظهرت النتائج أن إعطاء عصير الرمان والفراولة عن طريق الفم لمدة 8 اسابيع أدى إلى نقص معنوى فى مستوى إنزيمات الکبد المرتفعة (اسبرتات أمينو ترانسفيريز٬ الانين أمينو ترانسفيريز والکالين فوسفاتيز) والبليروبين الکلى في المصل ٬ بينما أدى إلى زيادة بروتينات الدم. وأدى أيضا إلى نقص معنوي فى دلائل سرطان الکبد بالمصل بينما أدى إلى زيادة نشاط الإنزيمات المضادة للأکسدة فى نسيج الکبد ونقص ترکيز مرکب 8- هيدروکسى – دى اوکسى جوانوزين. وأظهر الفحص الهستوباثولوجى وجود تحسن أو إختفاء التغيرات المرضية المحدثة بمرکب نيتروز داى إ يثيل أمين فى نسيج کبد الفئران. ودلت النتائج على أن عصير الرمان والفراولة لهما تأثر واقي ضد سرطان للکبد. وأشارت النتائج إلى أن آليات عمل عصير الرمان والفراولة کمضاد للسرطان قد تکون عن طريق منع أکسدة الدهون بنسيج الکبد وزيادة نشاط اﻹنزيمات المضادة للأکسدة وإحداث موت مبرمج في خلايا الکبد. وتوصى هذه الدراسة أن شرب عصير الرمان والفراولة قد يکون مفيدا للمرضى الذين يعانون من سرطان الکبد.

Correlation of five secretory proteins with the nasopharyngeal carcinoma metastasis and the clinical applications.

In our previous study, five different secretory proteins, including GSN, ADAMTSL4, CALR, PPIA and TXN, have been identified to be associated with the nasopharyngeal carcinoma (NPC) metastasis. In this work, the 5 proteins were further investigated. Bioinformatics analysis suggested that they might play an important role in the process of NPC development. Western blotting analysis showed that all of these 5 targets could be secreted into extracellular by both high metastatic NPC 5-8F cells and non-metastatic NPC 6-10B cells. Except for GSN, the expressions of ADAMTSL4, CALR, PPIA and TXN proteins in extracts of the 5-8F and 6-10B cells were significantly different (P < 0.05). Thus, the expressions of these 4 differentially expressed proteins were further tested in a cohort of NPC tissue specimens. The results indicated that the expression levels of ADAMTSL4 and TXN were highly correlated with the lymph node and distant metastasis (P<0.05) in NPC patients. Moreover, Enzyme-linked immunosorbent assay (ELISA) was used to investigate the concentrations of the ADAMTSL4 and TXN in serum specimens of NPC patients. The results revealed that serum ADAMTSL4 expression level was closely correlated with lymph node metastasis and clinical stage (P<0.05) in NPC patients, and it was able to discriminate metastasis NPC from non-metastasis NPC with a sensitivity of 75.6% and a specificity of 64.7%. The present data show for the first time that the ADAMTSL4 and TXN may be novel and potential biomarkers for predicting the NPC metastasis.Furthermore, the serum ADAMTSL4 could be a potential serum tumor biomarker for prognosis of NPC.

The implication of tumor biomarker CA19-9 in the diagnosis of intracranial epidermoid cyst.

ObjectThe diagnosis of intracranial epidermoid cyst (IEC) relies solely on MRI, which is time and money consuming. The application of tumor biomarkers in IEC has never been systematically studied. Here we screened a group of commonly used tumor biomarkers to assess their diagnostic value in IEC.ResultsSerum tumor biomarkers were assessed in 42 IECs and 42 paired healthy controls. Only serum CA19-9 level was significantly higher in the IEC group (median 20.3U/ml vs. 6.5U/ml, p < 0.001). Area under curve for CA19-9 was 0.806 (95% CI 0.700–0.912), with cutoff value of 13.15 U/ml (sensitivity 71.4%, specificity 97.6%). Tumor size was significantly different between CA19-9 positive and CA19-9 negative groups(64.14 ± 67.91cm3 vs. 19.43 ± 13.76 cm3, p = 0.04) and linear regression analysis revealed a positive correlation. Neither the extent of resection nor recurrence rate showed any significant difference between the two groups.MethodsThis is a retrospective study of IEC patients treated between 2009 and 2014. We analyzed the expression of common serum tumor biomarkers, including carbohydrate antigen 19–9 (CA19-9), carcinoembryonic antigen, carbohydrate antigen125 and squamous cell carcinoma in both IEC and healthy control group. Receiver operating characterisitics curves were constructed to evaluate the diagnostic accuracy.ConclusionsOur data indicated that for serum CA19-9 level higher than 13.15U/ml, after excluding the possibility of gastrointestinal system tumor, lung cancer, inflammation and other related diseases, the existence of IEC should be considered. Further prospective study is needed to gain more understanding of the value of CA19- 9 in postoperative evaluation and surveillance.

Associations between serum CA724 and HER2 overexpression among stage II-III resectable gastric cancer patients: an observational study.

ObjectivesAssociations between serum tumor biomarkers and human epidermal growth factor receptor 2 (HER2) overexpression among locally advanced gastric cancer patients were yet to be determined and therefore warranted investigation.ResultsA total of 318 patients were analyzed. The odds ratios of CA724 were 4.79 (95% CI 1.55–14.79) and 6.29 (1.40–28.19) in comparing the HER2 (2+/3+) and HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the four biomarkers yielded slightly but not significantly greater areas under the curve (AUC = 0.83; 0.71–0.94) than that of serum CA724 alone (0.80; 0.68–0.91); however, an index generated from the combination had better diagnostic performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or CA125 alone was not associated with HER2 overexpression. Leave-one-out cross-validation found a consistent association between serum CA724 and HER2 (2+/3+) overexpression.MethodsPatients undergoing radical gastrectomy from 8/2012 to 12/2013 and with pathological stage II–III gastric cancer were retrospectively analyzed. HER2 expression of the surgical samples was estimated using immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively tested. Internal validation was performed using the leave-one-out approach.ConclusionsSerum CA724 is significantly associated with the overexpression of HER2 among locally advanced gastric cancer patients. The combination of CA724, CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2 overexpression. External validation and further investigation of the biological mechanisms of these associations are required.

Efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy for the treatment of malignant ascites: a midterm study of 36 patients.

BackgroundThis study aimed to evaluate the efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for the treatment of malignant ascites (MA).MethodsBetween July 2011 and June 2013, 36 MA patients were prospectively and consecutively hospitalized for three cycles of elective CHIPC under ultrasound guidance, maintained at a constant flow rate of 400–600 mL/min normal saline containing 5-fluorouracil plus mitomycin or carboplatin and at a constant temperature of 43°C±0.2°C, for 90 minutes. Main outcome measures were ascites resolution, Karnofsky performance status (KPS), and serum tumor biomarkers at 2 weeks after the last cycle of CHIPC. All the patients underwent uneventful CHIPC as scheduled, and vital signs remained stable over CHIPC.ResultsAt 2 weeks after the last cycle of CHIPC, MA completely and partially resolved in 26 (72.2%) patients and eight (22.2%) patients, respectively; mean KPS score increased from pretreatment 61±9 to posttreatment 76±9 (P<0.001), and serum carcinoembryonic antigen and carbohydrate antigens 12-5 and 19-9 significantly decreased (all P<0.01).ConclusionThe current study indicated that ultrasound-guided CHIPC is an effective and safe palliative treatment modality for MA with respect to MA resolution, patient’s general well-being, and systemic disease control. The long-term benefit of CHIPC on overall survival remains to be investigated in MA patients.

Screening and Identifying a Novel ssDNA Aptamer against Alpha-fetoprotein Using CE-SELEX.

Alpha-fetoprotein (AFP) is a liver cancer associated protein and has long been utilized as a serum tumor biomarker of disease progression. AFP is usually detected in HCC patients by an antibody based system. Recently, however, aptamers generated from systematic evolution of ligands by exponential enrichment (SELEX) were reported to have an alternative potential in targeted imaging, diagnosis and therapy. In this study, AFP-bound ssDNA aptamers were screened and identified using capillary electrophoresis (CE) SELEX technology. After cloning, sequencing and motif analysis, we successfully confirmed an aptamer, named AP273, specifically targeting AFP. The aptamer could be used as a probe in AFP immunofluorescence imaging in HepG2, one AFP positive cancer cell line, but not in A549, an AFP negative cancer cell line. More interesting, the aptamer efficiently inhibited the migration and invasion of HCC cells after in vivo transfection. Motif analysis revealed that AP273 had several stable secondary motifs in its structure. Our results indicate that CE-SELEX technology is an efficient method to screen specific protein-bound ssDNA, and AP273 could be used as an agent in AFP-based staining, diagnosis and therapy, although more works are still needed.

Increased serum carcinoembryonic antigen level can predict poor survival of patients with small cell lung cancer

Increased serum tumor biomarkers are usually associated with huge tumor burden, but the prognostic value of these markers remains controversial. The serum levels of carcinoembryonic antigen (CEA), nerve cell-specific enolase, and lactate dehydrogenase in 281 patients with small cell lung cancer (SCLC) were analyzed in this study. Increased serum CEA levels were observed in 92 (32.7%) patients. Survival was superior in patients with normal serum CEA levels compared with those with increased serum CEA levels. The median survival time, 2-year overall survival (OS) rate, and 3-year OS rate were 19.1 months vs 14.6 months, 42.7% vs 28.3%, and 30.6% vs 14.1%, respectively (P = 0.002). In multivariate analysis, extensive-stage (ES)-SCLC (hazard ratio [HR] = 1.936, P = 0.001), an increased serum CEA level (HR = 1.432, P = 0.021) at diagnosis, and <4 cycles of chemotherapy (ChT) (HR = 0.432, P = 0.001) were independent negative prognostic factors for the OS. Additionally, normal CEA level (HR = 1.678, P = 0.012), treatment modalities including surgery (HR = 1.595, P = 0.049), and ≥ 4 cycles of ChT (HR = 1.880, P = 0.004) were independent positive prognostic factors for OS in patients with local disease. In the subgroup with ES-SCLC, normal serum CEA level (HR = 1.608, P = 0.043), thoracic radiation therapy (HR = 1.744, P = 0.005), and ≥ 4 cycles of ChT (HR = 2.626, P = 0.001) were independent positive prognostic factors for OS.

Advances in Molecular Biomarkers for Gastric Cancer.

Gastric cancer (GC) is the second most frequent oncological cause of death, the fifth most common malignancy in the world, and accounts for 6.8% of all tumors. As an aggressive disease, GC is often diagnosed at an advanced stage, which is why it is a major cause of cancer-related death. In the last several decades, the incidence of GC has decreased, which should be credited to advances in diagnostic and therapeutic technologies including tumor-marker detection systems, imaging modalities, pathological methods, gastroscopy, and particularly surgical and pharmacologic interventions. Because they are economical, convenient, and noninvasive, the detection of conventional serum tumor biomarkers (e.g., CEA, CA19-9, and CA72-4) has been widely employed in the diagnosis and evaluation of GC. However, due to their poor specificity and sensitivity, these molecular markers cannot meet the demand of early GC detection. Hence, new and reliable tumor biomarkers are desperately needed. This review systematically summarizes the three most commonly used biomarkers of GC (e.g., CEA, CA19-9, and CA72-4) and addresses two categories of potential molecular biomarkers for the diagnosis of GC: microRNA and methylated DNA.

Reduction of Serum Cytokeratin-3A9 is Associated with Chemotherapeutic Response in Patients with Non-Small Cell Lung Cancer.

Many tumor markers have been analyzed for applications in diagnosis, prognosis, and monitoring of cancer. Currently chemotherapy is routinely performed for patients with non-small cell lung cancer (NSCLC). The purpose of this study was to examine the serum tumor biomarker of cytokeratin (CK)-3A9 level in patients with NSCLC and its potential correlation with chemotherapeutic response. The serum samples of 196 NSCLC patients, 84 healthy controls, and 87 benign lung disease patients were provided for measurement of CK-3A9 and carcinoembryonic antigen (CEA). Serum CK-3A9 concentration was examined using a chemoluminescent method. The potential correlation between serum CK18-3A9 concentration and chemotherapeutic response was analyzed in 124 patients with advanced NSCLC (stages III and IV). The serum CK-3A9 levels in NSCLC patients pre-chemotherapy were significantly higher than those of healthy controls and benign lung disease patients (p < 0.01). CK-3A9 was related to Union for International Cancer Control (UICC) stages (p < 0.01) and histological classification (p < 0.05), but not related to age, gender, smoking status, and chemotherapy regimen (all p > 0.05). The testing results of serum CK-3A9 levels showed a higher sensitivity than that for CEA (48.2% and 39.5%, respectively). The chemotherapeutic response in the 124 patients with advanced NSCLC included 0 complete response (CR), 50 partial response (PR), 65 no change (NC), and 9 progression disease (PD). Post-chemotherapy CK-3A9 levels were significantly decreased compared to pre-chemotherapy (p < 0.05). The serum CK-3A9 levels in patients who achieved PR declined significantly compared to those who did not respond (SD + PD) after 2 cycles chemotherapy (p < 0.05). CK-3A9 appeared to be a new biomarker for reliable, cost-effective prediction of the efficacy of chemotherapy in patients with advanced NSCLC, although the results should be confirmed in larger studies.

A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer.

To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) through progress-free survival, changes in tumor marker expression and adverse drug reactions. A total of 59 NSCLC patients were randomized into two groups. The treatment group (n = 30) received nimotuzumab (200 mg) with docetaxel (60 mg/m2) and carboplatin (area under curve = 5), whereas the control group (n = 29) received chemotherapy at the same dosage. All patients received two cycles of treatment lasting for 42 days. The serum tumor biomarker levels were measured on the day before treatment and at 60 days after treatment. The efficacy of treatment for the treatment and control groups were 36.7% and 27.6%, respectively; this difference was not statistically significant. However, progression-free survival (PFS) was significantly prolonged by 1 month in the treatment group. Peripheral blood CYFRA21-1 decreased significantly during treatment with a more extensive decrease in the treatment group, although the difference between the groups was not statistically significant. The neuron-specific enolase levels significantly decreased across all 59 patients. The carcinoembryonic antigen levels decreased significantly in the treatment group, but remained stable in the control group throughout the treatment period. Nimotuzumab was well tolerated by patients with only three cases of Grades I and II skin rash and no other toxic symptoms. Nimotuzumab with docetaxel and carboplatin can enhance the short-term clinical efficacy by extending the duration of PFS and was generally well tolerated by patients.

Carbohydrate antigens as potential biomarkers for the malignancy in patients with idiopathic deep venous thrombosis: a retrospective cohort study.

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.

Investigation on the application significance of serum tumor biomarker HE4 detection in the diagnosis of lung cancer

Objective To investigate the expression level of tumor biomarker human epididymis protein 4( HE4)in tissue and serum of patients with lung cancer and its role in differential diagnosis of lung cancer. Methods HE4 expressions in lung adenocarcinoma,lung squamous cell carcinoma and cancer-adjacent tissues were detected by immunohistochemistry,and serum HE4 levels were determined in 214 patients with lung cancer and 76 healthy subjects by enzyme-linked immunobsorbent assay( ELISA). Simultaneously,the serum levels of squamous cell carcinoma antigen( SCC),carcinoembryonic antigen( CEA),cytokeratin 19 fragment( CYFRA21-1) and neuron-specific enolase( NSE) were determined. The results were compared and analyzed among the groups. Results Lung adenocarcinoma tissues showed stronger positive staining than lung squamous cell carcinoma tissues,and the negative staining was shown in cancer-adjacent tissues. The level of serum HE4 in lung cancer patients[85. 04( 64. 91,118. 40) pmol /L] was significantly higher than that of healthy controls [48. 48( 43. 12,58. 81) pmol /L,P 0. 01]. HE4 had a better diagnosis efficiency than CYFRA21-1 and CEA in non-small cell lung cancer through receiver operating characteristic( ROC) curve analysis. The positive rate of combined detection of SCC,CEA,CYFRA21-1 and NSE was 79.44% for lung cancer. However,HE4 improved the positive rate to 89. 72% when combined with this biomarker panel. In the diagnosis of lung adenocarcinoma,the positive rate of combined detection of CEA and CYFRA21-1 was 68. 46%.Moreover,HE4 improved the positive rate to 82. 31% when combined with this biomarker panel. Conclusions HE4,as a biomarker of lung cancer,is a useful indicator for the early diagnosis of lung cancer.

Progress on serum tumor biomarkers of endometrial carcinoma

Serum tumor biomarkers are significant for the early diagnosis and treatment,preoperative evaluation,prognosis prediction and relapse surveillance of endometrial carcinoma.Recently,serum CA125 and human epididymal secretory protein 4 are widely recognized as closely related with staging,metastasis and prognosis of endometrial cancer.In addition,the serum miRNAs are characterized by their features of high stability and specificity.Omics studies will be helpful for the general assessment of the initiation and progression of endometrial cancer.Insights into these two aspects will facilitate the identifications of new biomarkers with higher sensitivity and specificity for endometrial carcinoma. Key words: Endometrial neoplasms; Tumor markers, biological; Serum

Differences in carcinoembryonic antigen levels between colon and rectal cancer.

The aim of the present study was to investigate the levels of the serum tumor biomarker carcinoembryonic antigen (CEA) in patients with carcinoma of the colon and rectum in different clinical stages. Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer worldwide and previous studies have reported rapidly updated therapeutic regimes. While the majority of studies focus on CRC as a single entity, certain studies distinguish colon cancer (CC) from rectal cancer (RC), as there is a hypothesis stating that CC and RC are two naturally different entities. CEA is reported to be an important tumor-associated antigen overexpressed in CRC, which is routinely detected as a significant indicator of CRC. Our study aimed to identify potential differences in the expression of CEA between CC and RC, which may, to some degree, reflect the natural differences between the two. We investigated 240 CRC cases between July, 2010 and December, 2012 from The First and Second Affiliated Hospitals of Dalian Medical University, including 117 CC and 123 RC patients with tumors classified by Duke's staging as A-D. The serum CEA level was measured preoperatively by radioimmunoassays as a routinely used auxiliary indicator. The expression of CEA differed between CC and RC, with the former exhibiting variation among the four stages, whereas no variation was observed in RC. In addition, there were differences between CC and RC regarding the CEA level in stage C and D. Furthermore, the CEA level in stage C of CC was significantly lower compared to that in any other stage. In conclusion, the intrinsic distribution of the CEA level between CC and RC suggests that CC and RC may be two naturally different entities; the significantly low CEA level in stage C of CC indicates that stage C may be crucial in the evolution of CC.

Prognostic value of serum leptin in advanced lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy.

Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman’s correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment.

Investigation of Combining Serum Tumor Biomarkers and Clinical Features for Elderly Lung Cancer Diagnosis and Classification

To evaluate the diagnosis model of serum tumor biomarker and several clinical features diagnose and classification for lung cancer, the solid protein chip technology (C-12) was used to detect the biomarkers of SF, CEA, CA242, NSE, CA125, CA19-9 and CA15-3 in serum and several clinical features of tumors and benign disease in elderly lung cancer patients were collected. Set up a discriminating analysis as a function diagnostic model in clinical elderly lung cancer diagnosis and sub-type discrimination. In combination of 2 obvious clinical indicators and 2 serum markers, it is possible to provide a diagnosis tool for lung cancer. With the help of mathematic model, it is promising to reduce the misjudgment risk based on the previous experience and therefore establish a reliable diagnosing function. This model is simple, cost-effective and easy to adapt in practice, and can also be used in screening of large population.

A critical review of the analytical approaches for circulating tumor biomarker kinetics during treatment

Changes in serum tumor biomarkers may indicate treatment efficacy. Traditional tumor markers may soon be replaced by novel serum biomarkers, such as circulating tumor cells (CTCs) or circulating tumor nucleic acids. Given their promising predictive values, studies of their kinetics are warranted. Many methodologies meant to assess kinetics of traditional marker kinetics during anticancer treatment have been reported. Here, we review the methodologies, the advantages and the limitations of the analytical approaches reported in the literature. Strategies based on a single time point were first used (baseline value, normalization, nadir, threshold at a time t), followed by approaches based on two or more time points [half-life (HL), percentage decrease, time-to-events…]. Heterogeneities in methodologies and lack of consideration of inter- and intra-individual variability may account for the inconsistencies and the poor utility in routine. More recently, strategies based on a population kinetics approach and mathematical modeling have been reported. The identification of equations describing individual kinetic profiles of biomarkers may be an alternative strategy despite its complexity and higher number of necessary measurements. Validation studies are required. Efforts should be made to standardize biomarker kinetic analysis methodologies to ensure the optimized development of novel serum biomarkers and avoid the pitfalls of traditional markers.