The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma.

OBJECTIVE: This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC). RESULTS: A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.

The Diagnostic Power of Circulating miR-1246 in Screening Cancer: An Updated Meta-analysis.

Background: MicroRNA-1246 (miR-1246), an oncomiR that regulates the expression of multiple cancer-related genes, has been attracted and studied as a promising indicator of various tumors. However, diverse conclusions on diagnostic accuracy have been shown due to the small sample size and limited studies included. This meta-analysis is aimed at systematically assessing the performance of extracellular circulating miR-1246 in screening common cancers. Methods: We searched the PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases for relevant studies until November 28, 2022. Then, the summary receiver operating characteristic (SROC) curves were drawn and calculated area under the curve (AUC), diagnostic odds ratio (DOR), sensitivity, and specificity values of circulating miR-1246 in the cancer surveillance. Results: After selection and quality assessment, 29 eligible studies with 5914 samples (3232 cases and 2682 controls) enrolled in the final analysis. The pooled AUC, DOR, sensitivity, and specificity of circulating miR-1246 in screening cancers were 0.885 (95% confidence interval (CI): 0.827-0.892), 27.7 (95% CI: 17.1-45.0), 84.2% (95% CI: 79.4-88.1), and 85.3% (95% CI: 80.5-89.2), respectively. Among cancer types, superior performance was noted for breast cancer (AUC = 0.950, DOR = 98.5) compared to colorectal cancer (AUC = 0.905, DOR = 47.6), esophageal squamous cell carcinoma (AUC = 0.757, DOR = 8.0), hepatocellular carcinoma (AUC = 0.872, DOR = 18.6), pancreatic cancer (AUC = 0.767, DOR = 12.3), and others (AUC = 0.887, DOR = 27.5, P = 0.007). No significant publication bias in DOR was observed in the meta-analysis (funnel plot asymmetry test with P = 0.652; skewness value = 0.672, P = 0.071). Conclusion: Extracellular circulating miR-1246 may serve as a reliable biomarker with good sensitivity and specificity in screening cancers, especially breast cancer.

Characteristics of Hepatitis B Virus Genotype and Sub-Genotype in Hepatocellular Cancer Patients in Vietnam.

Untreated chronic hepatitis B virus (HBV) infection can lead to chronic liver disease and may progress to cirrhosis or hepatocellular carcinoma (HCC). HBV infection has been prevalent in Vietnam, but there is little information available on the genotypes, sub-genotypes, and mutations of HBV in patients with HBV-related HCC confirmed by histopathological diagnosis. We studied the molecular characteristics of HBV and its genetic variants in Vietnamese HCC patients after liver tumor resection. We conducted a descriptive cross-sectional study on 107 HBV-related HCC hospitalized patients from October 2018 to April 2019. The specimens collected included EDTA anticoagulant blood and liver tissues. Extracted HBV DNA was subjected to whole genome sequencing by the Sanger method. We discovered 62 individuals (57.9%) with genotype B and 45 patients (42.1%) with genotype C, with only sub-genotypes B4 and C1. Among the mutations, the double mutation, A1762T-G1764A, had the most significant frequency (73/107 samples; 68.2%) and was higher in genotype C than in genotype B (p < 0.001). The most common genotypes found in HCC patients in this investigation were B and C, with sub-genotypes B4 and C1 for each. The prevalence of genotype B4 was greater in HBV-infected Vietnamese HCC patients.

EGFR-plasma mutations in prognosis for non-small cell lung cancer treated with EGFR TKIs: A meta-analysis.

BACKGROUND: The plasma-based epidermal growth factor receptor (EGFR) mutation testing is approved recently to use in clinical practice. However, it has not been used as a prognostic marker yet because of contradictory results. AIM: This meta-analysis aims to clarify the role of the EGFR-plasma test in prognosis for non-small cell lung cancer (NSCLC) who have mutant tumors and receive EGFR tyrosine kinase inhibitors (TKIs). METHODS AND RESULTS: The PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases were searched for relevant studies by April 10, 2021. The hazard ratio (HR) from reports was extracted and used to assess the correlation of EGFR-plasma status with progression-free survival (PFS) and overall survival (OS). A total of 35 eligible studies with 4106 patients were enrolled in the final analysis. Patients with concurrent EGFR mutations in pretreatment plasma have shorter PFS (HR = 2.00, 95% confidence interval [CI]: 1.73-2.31, p < .001) and OS time (HR = 2.31, 95% CI: 1.89-2.83, p < .001) compared to the tumor-only mutation cases. Besides, the persistence of EGFR-activating mutations in post-treatment plasma is associated with worse PFS (HR = 3.84, 95% CI: 2.96-4.99, p < .001) and OS outcome (HR = 3.22, 95% CI: 2.35-4.42, p < .001) compared to others. Notably, the prognostic value of the EGFR-plasma test is also validated in treatment with third-generation EGFR TKI and significance regardless of different detection methods. CONCLUSION: The presence of EGFR-plasma mutations at pretreatment and after EGFR TKI initiation is the worse prognostic factor for PFS and OS in NSCLC.

The diagnostic power of CD117, CD13, CD56, CD64, and MPO in rapid screening acute promyelocytic leukemia.

OBJECTIVE: The same immuno-phenotype between HLA-DR-negative acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) causes APL rapid screening to become difficult. This study aimed to identify the associated antigens for APL and the best model in clinical uses. RESULTS: A total of 36 APL (PML-RARA+) and 29 HLA-DR-negative non-APL patients enrolled in this study. When a cut-off point of 20% events was applied to define positive or negative status, APL and non-APL patients share a similar immuno-phenotype of CD117, CD34, CD11b, CD13, CD33, and MPO (P > 0.05). However, expression intensity of CD117 (P = 0.002), CD13 (P < 0.001), CD35 (P < 0.001), CD64 (P < 0.001), and MPO (P < 0.001) in APL are significantly higher while CD56 (P = 0.049) is lower than in non-APL subjects. The Bayesian Model Averaging (BMA) analysis identified CD117 (≥ 49% events), CD13 (≥ 88% events), CD56 (≤ 25% events), CD64 (≥ 42% events), and MPO (≥ 97% events) antigens as an optimal model for APL diagnosis. A combination of these factors resulted in an area under curve (AUC) value of 0.98 together with 91.7% sensitivity and 93.1% specificity, which is better than individual markers (AUC were 0.76, 0.84, 0.65, 0.82, and 0.85, respectively) (P = 0.001).

Smoking habit and chemo-radiotherapy and/or surgery affect the sensitivity of EGFR plasma test in non-small cell lung cancer.

OBJECTIVE: This study aimed to identify the influential factors for the sensitivity of epidermal growth factor receptor (EGFR) plasma test in non-small cell lung cancer (NSCLC). The mutations were detected in tumor tissue and matched plasma samples from 125 newly diagnosed adenocarcinoma, clinical-stage IIIB-IV patients, and compared the diagnostic values of EGFR plasma test between groups of clinical characteristics. The influential factors for the sensitivity were identified and assessed by logistic regression. RESULTS: EGFR mutations were detected in 65 (52.0%) tumor tissue and 50 (40.0%) matched plasma samples (P = 0.028). Compared to the tissue method, the concordance rate, sensitivity, and specificity of the EGFR plasma test were 86.4%, 75.4%, and 98.3%, respectively. Notably, we found that sensitivity of the test is higher in non-smokers (84.1%) compared to smokers (57.1%, P = 0.018), and in treatment naïve subjects (85.7%) compared to whom undergone chemo-radiotherapy with/without surgery before testing (56.5%, P = 0.009). Furthermore, the highest sensitivity was attained in patients without these two factors (90.3%), whilst the lowest value was noted in those with both factors (40.0%, P = 0.004). The multivariable analysis confirmed that smoking habit and treatment history have independently negative impacts on sensitivity (OR = 0.24, P = 0.019, and OR = 0.36, P = 0.047, respectively).

Emergence role of nucleated red blood cells in molecular response evaluation for chronic myeloid leukemia.

PURPOSE: To investigate and evaluate the role of nucleated red blood cells (NRBCs) and other markers in predicting remission failure in chronic myeloid leukemia (CML) patients treated with imatinib. METHODS: Seventy-one CML patients with BCR-ABL(+) in bone marrow cells were selected for this study. Molecular response evaluations were done every three months according to the recommendations of European LeukemiaNet (ELN). Patients were defined as remission failure if BCR-ABL transcripts >10% after 6 months (T6), >1% after 12 months (T12), and >0.1% after 18 (T18) months of treatment. The logistic regression was used to determine the optimal cut-off point of each marker and test the association of marker level with remission failure. RESULTS: The median NRBC, white blood cells, blast cells, basophils, and platelets were declined parallel with the decreases of BCR-ABL transcripts in bone marrow cells after 6 months of treatment (P<0.001). In addition, NRBC was almost not found in the blood of patients who archived good response at T6, T12, and T18 time-points. Interestingly, patients with a high level of NRBC (cut-off: 0.003×109/L) have higher BCR-ABL transcripts compared to others. The elevated NRBC at T6 (OR=6.49, P=0.042), T12 (OR=6.73, P=0.007), and T18 (OR=5.96, P=0.009) time-points was identified as an independent factor for the remission failure. CONCLUSION: The results of this study showed that a high number of NRBC in peripheral blood of CML patients is associated with higher BCR-ABL transcripts in bone marrow cells. The elevated NRBC might serve as an independent marker for molecular remission failure in CML.

EGFR plasma mutation in prediction models for resistance with EGFR TKI and survival of non-small cell lung cancer.

BACKGROUND: This study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. A total of 94 Adenocarcinoma, clinical stage IV NSCLC patients with either E19del or L858R mutation were admitted to the prospective study from Jan-2016 to Jul-2018. EGFR mutations in plasma were detected by scorpions ARMS method. The Kaplan-Meier and Cox regression methods were used to estimate and test the difference of progression-free survival (PFS) and overall survival (OS) between groups. The prognostic power of each factor was appraised by the Bayesian Model Averaging (BMA) method. RESULTS: Among 94 patients, 28 cases still are good responses according to the RECIST criteria and negative for EGFR mutations in plasma. Of 66 resistant patients, EGFR mutations were positive in plasma of 57 cases (86.4%) which was higher than the value of pre-treatment (48.5%). Of which, 17 patients (25.8%) have the occurrence of EGFR mutations in plasma earlier than progression 2.1 (0.6-7.9) months. The secondary T790M mutation was found in the plasma of 32 cases (48.5%). Median PFS and OS for the study subjects were 12.9 (11.0-14.2) and 29.5 (25.2-41.3) months, respectively. The post-treatment EGFR plasma test with brain and new metastasis were detected as independent prognostic factors for worse PFS (P = 0.008, 0.016 and 0.028, respectively). While EGFR plasma (P = 0.044) with bone metastasis at baseline (P = 0.012), new metastasis (P = 0.003), and high cfDNA concentration (P = 0.004) serve as the worse survival factors, surgery treatment helps to prolong OS in NSCLC treated with EGFR TKI (P = 0.012). BMA analysis identified EGFR plasma test as the strongest prognostic factor for both PFS and OS (possibility of 100% and 99.7%, respectively). CONCLUSIONS: EGFR plasma test is the powerfully prognostic factor for early resistance with EGFR TKI and worse survival in NSCLC regardless of clinical characteristics.

The prognostic impact of neutrophil to lymphocyte ratio in advanced non-small cell lung cancer patients treated with EGFR TKI.

PURPOSE: To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI). PATIENTS AND METHODS: One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either EGFR exon 19 deletion (E19del) or EGFR exon 21 L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers. The Kaplan-Meier statistics and Cox regression model were used to test the differences of progression-free survival (PFS) between groups by the optimal cutoff point of biomarkers. RESULTS: The median values of white blood cell (WBC), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) in NSCLC patients tended to be reduced after 3 months treated with EGFR TKI and increased conversely when the disease develops progression (P<0.001). With an optimal cutoff point of 2.96, NLR is the best prognostic marker in prediction of clinical response among the investigated markers (area under the curve [AUC]=0.873, 95% CI: 0.821-0.926, P<0.001), and it is an independent predictive marker (OR=3.52, 95% CI: 1.42-8.71, P<0.001). With optimal cutoff point of 0.38, MLR is also a predictive marker in response evaluation (AUC=0.762, 95% CI: 0.691-0.832). Univariate analyses have shown that the larger tumor size (>3cm) and the high level of pretreatment NLR were associated with the shortening of PFS (HR=2.24, 95% CI: 1.04-4.83, P=0.039 and HR=2.67, 95% CI: 1.41-5.03, P=0.006, respectively). Multivariate analysis has shown that the elevated NLR is an independent prognostic marker for worse PFS of NSCLC patients treated with EGFR TKI (HR=2.15, 95% CI: 1.15-3.99, P=0.016). CONCLUSION: NLR and MLR are valuable markers in response evaluation for NSCLC patients treated with EGFR TKI. The elevated NLR is also an independent prognostic factor for worse survival.