Diagnostic Value of Immunohistochemical Markers in Four-grade Histological Classification of Hepatocellular Carcinoma

Abstract Backgrounds: Accurate differential diagnosis regarding histological grades of hepatocellular carcinoma (HCC) is critical for targeted treatment and prognostic evaluation. However, the currently used descriptive diagnosis of histological grading have to observe tedious item of neovascularization, stromal invasion, cellular and structural atypia, which have drawbacks of subjectivity and error-prone. Immunohistochemical (IHC) markers-based diagnosis only needs to determine whether there is staining in the cell membrane, cytoplasm and / or nucleus. Using IHC markers targeted heat shock protein (HSP)70, glypican (GPC)3, glutamine synthetase (GS), and organic anion transport peptide (OATP), we sought to establish an easy method for the diagnosis of the histopathological grades and further explore the best efficacy by their combined or independent application.Methods: We retrospectively conducted a study of 157 patients with 200 histologically confirmed HCCs, which were classified into early (n= 45), well (n=31), moderately (n=68), and poorly (n=56) differentiated (diff.) HCC. The sensitivity, specificity, accuracy of HSP70, GPC3, GS and OATP on each histological grade were examined. Results: HSP70 and GPC3 showed difference in most histological grades of HCC ( P < 0.05). GS distinguished early HCC from three other histological grades (p < 0.01). OATP8 only differentiated early HCC from poorly diff. HCC (P=0.019). When any two of the three indicators (HSP, GPC3, and GS) were negatively expressed, the diagnostic efficacy of early HCC was the highest, with an area under the curve (AUC) of 0.802 and accuracy of 80.5%. The optimal efficacy for poorly diff. HCC detection was obtained when both GPC3 and HSP70 were positively expressed (74.4% accuracy; AUC = 0.703). However, for well and moderately diff. HCC, a relative satisfactory AUC value (>0.60) failed to yield either by the independent or combined diagnosis of any IHC indicators.Conclusion: Using GS, HSP70, and GPC3, early and poorly diff. HCC can be properly diagnosed. IHC markers might be a potential alternative tool for histological differential diagnosis of HCC.

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Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma

Diagnostics ◽

10.3390/diagnostics10050321 ◽

2020 ◽

Vol 10 (5) ◽

pp. 321 ◽

Cited By ~ 5

Author(s):

Feiqian Wang ◽

Kazushi Numata ◽

Masayuki Nakano ◽

Mikiko Tanabe ◽

Makoto Chuma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Area Under The Curve ◽

Diagnostic System ◽

Diagnostic Value ◽

Imaging Method ◽

Multicenter Studies ◽

Diagnostic Efficacy ◽

Portal Phase ◽

Contrast Enhanced ◽

Early Hcc

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

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Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

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Diagnostic Value of C-Reactive Protein in Discrimination between Uncomplicated and Complicated Parapneumonic Effusion

Diagnostics ◽

10.3390/diagnostics10100829 ◽

2020 ◽

Vol 10 (10) ◽

pp. 829

Author(s):

Yana Kogan ◽

Edmond Sabo ◽

Majed Odeh

Keyword(s):

Area Under The Curve ◽

Diagnostic Value ◽

Parapneumonic Effusion ◽

C Reactive Protein ◽

Diagnostic Efficacy ◽

Reactive Protein ◽

Significant Difference ◽

Study Population ◽

Complicated Parapneumonic Effusion

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.

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Diagnostic efficacy of serum and urinary netrin-1 in the early detection of diabetic nephropathy

Journal of Investigative Medicine ◽

10.1136/jim-2021-001785 ◽

2021 ◽

pp. jim-2021-001785

Author(s):

Rasha A Elkholy ◽

Reham L Younis ◽

Alzahraa A Allam ◽

Rasha Youssef Hagag ◽

Muhammad Tarek Abdel Ghafar

Keyword(s):

Diabetic Nephropathy ◽

Early Detection ◽

Characteristic Curve ◽

Fasting Blood Glucose ◽

Area Under The Curve ◽

Diagnostic Value ◽

Control Group ◽

Diagnostic Efficacy ◽

Significant Difference ◽

Patients With Diabetes

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. Serum and urinary levels of netrin-1 were measured by ELISA. The mean levels of serum and urinary netrin-1 were significantly higher in the microalbuminuric and macroalbuminuric patients with DN than those in the normoalbuminuric patients with T2DM, with the highest values detected in macroalbuminuric patients with DN. Urinary netrin-1 level was significantly higher in the normoalbuminuric T2DM group than control group, whereas no significant difference existed regarding serum netrin-1 level. In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.

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Clinically Correlated MicroRNAs in the Diagnosis of Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2018/5930951 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Min Jiang ◽

Xuelian Li ◽

Xiaowei Quan ◽

Xiaoying Li ◽

Baosen Zhou

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Value ◽

Small Cell ◽

Diagnostic Tools ◽

Small Cell Lung ◽

Diagnostic Efficacy

(1) Background. Non-small cell lung cancer (NSCLC) has a high mortality rate. MiRNAs have been found to be diagnostic biomarkers for NSCLC. However, controversial results exist. We conducted this meta-analysis to evaluate the diagnostic value of miRNAs for NSCLC.(2) Methods. Databases and reference lists were searched. Pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to examine the general diagnostic efficacy, and subgroup analysis was also performed.(3) Results. Pooled SEN, SPE, and AUC were 85%, 88%, and 0.93, respectively, for 71 studies. Multiple miRNAs (AUC: 0.96) obtained higher diagnostic value than single miRNA (AUC: 0.86), and the same result was found for Caucasian population (AUC: 0.97) when compared with Asian (AUC: 0.91) and Caucasian/African population (AUC: 0.92). MiRNA had higher diagnostic efficacy when participants contained both smokers and nonsmokers (AUC is 0.95 for imbalanced group and 0.91 for balanced group) than when containing only smokers (AUC: 0.90). Meanwhile, AUC was 0.91 for both miR-21 and miR-210.(4) Conclusions. Multiple miRNAs such as miR-21 and miR-210 could be used as diagnostic tools for NSCLC, especially for the Caucasian and nonsmoking NSCLC.

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Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma

Gut ◽

10.1136/gutjnl-2017-315084 ◽

2018 ◽

Vol 68 (6) ◽

pp. 1014-1023 ◽

Cited By ~ 102

Author(s):

Zhigang Ren ◽

Ang Li ◽

Jianwen Jiang ◽

Lin Zhou ◽

Zujiang Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Gut Microbiome ◽

Cross Validation ◽

Area Under The Curve ◽

Northwest China ◽

Central China ◽

Advanced Hcc ◽

Non Invasive ◽

Faecal Samples ◽

Early Hcc

ObjectiveTo characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of microbiome as non-invasive biomarkers for HCC.DesignWe collected 486 faecal samples from East China, Central China and Northwest China prospectively and finally 419 samples completed Miseq sequencing. We characterised gut microbiome, identified microbial markers and constructed HCC classifier in 75 early HCC, 40 cirrhosis and 75 healthy controls. We validated the results in 56 controls, 30 early HCC and 45 advanced HCC. We further verified diagnosis potential in 18 HCC from Xinjiang and 80 HCC from Zhengzhou.ResultsFaecal microbial diversity was increased from cirrhosis to early HCC with cirrhosis. Phylum Actinobacteria was increased in early HCC versus cirrhosis. Correspondingly, 13 genera including Gemmiger and Parabacteroides were enriched in early HCC versus cirrhosis. Butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early HCC versus controls. The optimal 30 microbial markers were identified through a fivefold cross-validation on a random forest model and achieved an area under the curve of 80.64% between 75 early HCC and 105 non-HCC samples. Notably, gut microbial markers validated strong diagnosis potential for early HCC and even advanced HCC. Importantly, microbial markers successfully achieved a cross-region validation of HCC from Northwest China and Central China.ConclusionsThis study is the first to characterise gut microbiome in patients with HCC and to report the successful diagnosis model establishment and cross-region validation of microbial markers for HCC. Gut microbiota-targeted biomarkers represent potential non-invasive tools for early diagnosis of HCC.

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Multiparameter Analysis Using 18F-FDG PET/CT in the Differential Diagnosis of Pancreatic Cystic Neoplasms

Contrast Media & Molecular Imaging ◽

10.1155/2021/6658644 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Guanyun Wang ◽

Haodan Dang ◽

Peng Yu ◽

Honghong Liu ◽

Yue Wu ◽

...

Keyword(s):

Differential Diagnosis ◽

Fdg Pet ◽

Diagnostic Value ◽

Combined Model ◽

Cystic Neoplasms ◽

Diagnostic Efficacy ◽

Multiple Parameters ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Purpose. To evaluate multiparametric analysis in differential diagnosis between pancreatic serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs) as well as the differentiation of the benign and malignant MCNs with 18F-FDG (18-fluorodeoxyglucose) PET/CT (positron emission tomography). Methods. Forty patients with total of 41 lesions (SCNs: 27/41; MCNs: 14/41), who were preoperatively examined with 18F-FDG PET/CT, were retrospectively analyzed. Multiple quantitative parameters using conventional and texture features were included. The combined model was established with complementary PET/MR parameters. The differential diagnostic efficacy of each independent parameter and the combined model were evaluated with receiver operating characteristic (ROC) analysis. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI) were used to evaluate improvement of diagnostic efficacy by using combination of multiple parameters. Results. Among all independent parameters, the percentile 5th (0.88 ± 0.38 vs 0.47 ± 0.23, P < 0.001 ) showed the highest discriminative diagnostic value. The combination of multiple parameters can improve the differential diagnostic efficacy of SCNs and MCNs (sensitivity = 71.4%, specificity = 77.8%, and AUC = 0.788), and the addition of texture parameters to the conventional parameters allowed a significant reclassification with IDI = 0.236 (95% CI: 0.095–0.377) and categorical NRI = 0.434 (95% CI: 0.030–0.838). SURmax (tumor to normal pancreas ratio, T/P) and SURmax (tumor to aorta ratio, T/A) both showed the highest discriminative diagnostic value (sensitivity = 100.0%, specificity = 70.0%, AUC = 0.900, and Youden index = 0.700) in the differential diagnosis of benign and malignant MCNs, with the cutoff values of 0.84 and 0.90, respectively. Conclusion.Combination of multiple parameters using 18F-FDG PET/CT could further improve differentiation between pancreatic SCNs and MCNs. SURmax (T/P) and SURmax (T/A) could improve differential diagnosis of benign and malignant MCNs.

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Role of ssDNA as a Noninvasive Indicator for the Diagnosis and Prognosis of Hepatocellular Carcinoma: An Exploratory Study

Disease Markers ◽

10.1155/2021/9958909 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Qi Zhao ◽

Yiqiu Xu ◽

Dandan Yuan ◽

Junjun Yang ◽

Ying Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Exploratory Study ◽

Magnetic Beads ◽

Area Under The Curve ◽

Radical Resection ◽

Diagnostic Value ◽

Healthy Individuals ◽

Diagnosis And Prognosis ◽

Imaging Results

Background and Aim. This exploratory study explored single-stranded DNA (ssDNA) for hepatocellular carcinoma (HCC) diagnosis and prognosis. Methods. This prospective study enrolled 102 patients with newly diagnosed HCC, 21 with cirrhosis, 20 with chronic hepatitis, 284 with nonliver diseases, and 45 healthy individuals at the Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University (May-October 2018). ssDNA was extracted using magnetic beads and quantified using the Qubit ssDNA assay. ssDNA levels were compared among the disease groups and in HCC vs. non-HCC. Receiver operating characteristic (ROC) curves were used to determine the diagnostic value of ssDNA. In patients with resectable HCC, ssDNA and α-fetoprotein (AFP) levels were measured during follow-up and compared with HCC recurrence detected by imaging. Results. The median ssDNA levels were higher in HCC than in healthy individuals, cirrhosis, and chronic hepatitis (median, 23.20 vs. 9.36, 9.64, and 9.76 ng/μL, respectively, P < 0.001 ). ssDNA levels in HCC were higher than those in cirrhosis and chronic hepatitis (both P < 0.001 ); there were no differences in ssDNA levels between healthy controls and patients with cirrhosis ( P = 0.15 ) or chronic liver disease ( P = 0.39 ). The area under the curve of ssDNA for HCC diagnosis was 0.909 (95% CI: 0.879-0.933). The ssDNA levels decreased by 3.19-fold ( P < 0.001 ) after HCC radical resection. In six patients, the ssDNA levels increased about 3-6 months before a recurrence was detected by AFP and imaging. Conclusions. ssDNA might be a noninvasive indicator for HCC diagnosis and prognosis. ssDNA could eventually be complementary to AFP levels and imaging, but confirmatory studies are necessary.

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Application of PCT, CRP and WBC levels in the differential diagnosis of acute bacterial, viral, and mycoplasmal respiratory tract infections

10.22541/au.162878993.35055514/v1 ◽

2021 ◽

Author(s):

Li Yang ◽

Min Lanfang ◽

Zhang Xin

Keyword(s):

Differential Diagnosis ◽

Respiratory Tract ◽

Bacterial Infections ◽

Respiratory Tract Infections ◽

Respiratory Infections ◽

Area Under The Curve ◽

Diagnostic Value ◽

Significant Difference ◽

Group A ◽

Tract Infections

Objective There is a lack of studies comparing Procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) levels in the differential diagnosis of acute bacterial, viral, and mycoplasmal respiratory infections. It is necessary to explore the correlation between above markers and different types of acute respiratory tract infections (ARTI). Methods 108 children with confirmed bacterial infection were regarded as group A, 116 children with virus infection were regarded as group B, and 122 children with mycoplasma infection were regarded as group C. The levels of PCT, CRP and WBC of the three groups were detected and compared. Results The levels of PCT, CRP and WBC in group A were significantly higher than those in groups B and C (P <0.05). The positive rate of combined detection of PCT, CRP and WBC was significantly higher than that of single detection. There was no significant difference of PCT, CRP and WBC levels between the group of Gram-positive (G+) bacteria infection and Gram-negative (G-) bacteria infection (P >0.05). ROC curve results showed that the area under the curve (AUC) of PCT, CRP and WBC for the diagnosis of bacterial respiratory infections were 0.65, 0.55, and 0.58, respectively. Conclusions PCT, CRP and WBC can be used as effective indicators for the identification of acute bacterial or no-bacterial infections in children. The levels of PCT and CRP have higher differential diagnostic value than that of WBC in infection, and the combined examination of the three is more valuable in clinic.

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Lack of Efficacy of Combined Carbohydrate Antigen Markers for Lung Cancer Diagnosis

Disease Markers ◽

10.1155/2020/4716793 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Zhineng Wen ◽

Ying Huang ◽

Zhougui Ling ◽

Jifei Chen ◽

Xiaomou Wei ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Markers ◽

Cell Lung Cancer ◽

Area Under The Curve ◽

Nonsmall Cell Lung Cancer ◽

Diagnostic Value ◽

Carbohydrate Antigen ◽

Ca 125 ◽

Chi Square ◽

Diagnostic Efficacy

Background. Lung cancer (LC) is top-ranked in cancer incidence and is the leading cause of cancer death globally. Combining serum biomarkers can improve the accuracy of LC diagnosis. The identification of the best potential combination of traditional tumor markers is essential for LC diagnosis. Patients and Methods. Blood samples were collected from 132 LC cases and 118 benign lung disease (BLD) controls. The expression levels of ten serum tumor markers (CYFR21, CEA, NSE, SCC, CA15-3, CA 19-9, CA 125, CA50, CA242, and CA724) were assayed, and that the expression in the levels of tumor markers were evaluated, isolated, and combined in different patients. The performance of the biomarkers was analyzed by receiver operating characteristic (ROC) analyses, and the difference between combinations of biomarkers was compared by Chi-square ( χ 2 ) tests. Results. As single markers, CYFR21 and CEA showed good diagnostic efficacy for nonsmall cell lung cancer (NSCLC) patients, while NSE and CEA were the most sensitive in the diagnosis of small cell lung cancer (SCLC). The area under the curve (AUC) value was 0.854 for the panel of four biomarkers (CYFR21, CEA, NSE, and SCC), 0.875 for the panel of six biomarkers (CYFR21, CEA, NSE, SCC, CA125, and CA15-3), and 0.884 for the panel of ten markers (CYFR21, CEA, NSE, SCC, CA125, CA15-3, CA19-9, CA50, CA242, and CA724). With a higher sensitivity and negative predictive value (NPV), the diagnostic accuracy of the three panels was better than that of any single biomarker, but there were no statistically significant differences among them (all P values > 0.05). However, the panel of six carbohydrate antigen (CA) biomarkers (CA125, CA15-3, CA19-9, CA50, CA242, and CA724) showed a lower diagnostic value (AUC: 0.776, sensitivity: 59.8%, specificity: 73.0%, and NPV: 60.4%) than the three panels ( P value < 0.05). The performance was similar even when analyzed individually by LC subtypes. Conclusion. The biomarkers isolated are elevated for different types of lung cancer, and the panel of CYFR21, CEA, NSE, and SCC seems to be a promising serum biomarker for the diagnosis of lung cancer, while the combination with carbohydrate antigen markers does not improve the diagnostic efficacy.

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