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.

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.