Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Reverse-transcriptase polymerase chain reaction versus chest computed tomography for detecting early symptoms of COVID-19. A diagnostic accuracy systematic review and meta-analysis

ABSTRACT BACKGROUND: A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS CoV-2, from nasopharyngeal swabs, is the current gold standard diagnostic test for this virus and has sensitivity of 60-70%. Some studies have demonstrated a significant number of false-negative RT-PCR tests while displaying significant tomographic findings, in the early days of symptoms of COVID-19. OBJECTIVE: To compare accuracy between RT-PCR and computed tomography (CT) for detecting COVID-19 in the first week of its symptoms during the pandemic. DESIGN AND SETTING: Systematic review of comparative studies of diagnostic accuracy within the Evidence-based Health Program of a federal university in São Paulo (SP), Brazil. METHODS: A systematic search of the relevant literature was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL and LILACS databases, for articles published up to June 6, 2020, relating to studies evaluating the diagnostic accuracy of RT-PCR and chest CT for COVID-19 diagnoses. The QUADAS 2 tool was used for methodological quality evaluation. RESULTS: In total, 1204 patients with COVID-19 were evaluated; 1045 had tomographic findings while 755 showed positive RT-PCR for COVID-19. RT-PCR demonstrated 81.4% sensitivity, 100% specificity and 92.3% accuracy. Chest CT demonstrated 95.3% sensitivity, 43.8% specificity and 63.3% accuracy. CONCLUSION: The high sensitivity and detection rates shown by CT demonstrate that this technique has a high degree of importance in the early stages of the disease. During an outbreak, the higher prevalence of the condition increases the positive predictive value of CT. REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/UNGHA in the Open Science Framework.

CT-guided microwave ablation and biopsy of highly suspected malignant ground-glass nodule of lung with co-axle technique / 中国介入影像与治疗学

Objective: To observe the feasibility of CT-guided microwave ablation and biopsy of highly suspected malignant pulmonary ground-glass nodule (GGN) with co-axle technique. Methods: Totally 54 patients with highly suspected malignant pulmonary single GNN (with diameter of 10-25 mm) were retrospectively analyzed, including 26 underwent CT-guidance microwave ablation and biopsy with co-axle technique (ablation synchronous biopsy group) and 28 underwent simple puncture biopsy (biopsy group). The rates of pathological diagnosis, hemorrhage and pneumothorax were compared between 2 groups. Results: All patients underwent successful operation, the success rate was both 100% in 2 groups. The rate of pathological diagnosis was 88.46% (23/26), of pneumothorax was 26.92% (7/26) in ablation synchronous biopsy group, while in biopsy group was 92.86% (26/28) and 32.14%(9/28), respectively (both P>0.05). The rate of hemorrhage in ablation synchronous biopsy group was 30.77%(8/26),lower than that of biopsy group (42.86% [12/28], χ2=5.962,P=0.028). Conclusion: CT-guided microwave ablation and biopsy of highly suspected malignant pulmonary GGN with co-axle technique is safe and effective with lower bleeding risk compared with biopsy alone.

Primary Pulmonary Extranodal Natural Killer/T-cell Lymphoma, Nasal Type Presenting as Diffuse Ground Glass Opacities: a Case Report

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL) is a rare type of lymphoma that accounts for only 5%–18% of all cases of non-Hodgkin lymphoma (NHL). In published series, 60%–90% of NK/T-cell lymphomas are localized to the nasal and upper airway. We describe a 55-year man who presented with cough, sputum, dyspnea on exertion, and a chest computed tomography scan shows diffuse ground glass opacities (GGOs), suggestive of an interstitial lung disease. He was treated with a corticosteroid and his symptoms improved. However, when the corticosteroid was tapered, his symptoms recurred. The patient underwent a surgical lung biopsy and ENKTCL was diagnosed. We present this case because ENKTCL involving only the lung is very rare but very informative. To our knowledge, our patient is the first case that primary pulmonary ENKTCL is presented with GGOs.

The Area of Ground Glass Opacities of the Lungs as a Predictive Factor in Acute Paraquat Intoxication

Even though plasma paraquat (PQ) levels have known to be an informative predictor, many patients succumb at low PQ levels in acute PQ intoxication. This study was designed to see whether the high resolution computerized tomography (HRCT) of the lungs would be a predictive measure in acute PQ intoxication. HRCT of the lungs was obtained from 119 patients with acute PQ intoxication on 7 days after PQ ingestion. The areas with ground glass opacities (GGOs) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems. Among 119 patients, 102 survived and 17 died. The plasma PQ levels were significantly higher in the non-survivors than in the survivors (2.6+/-4.0 microgram/mL vs. 0.2+/-0.4 microgram/mL, P=0.02). The area with GGOs was 2.0+/-6.4% in the survivors and 73.0+/- 29.9% in the non-survivors (P<0.001). No patients survived when the area with GGOs was more than 40% but all of the patients survived when the area affected by GGOs was less than 20%. In conclusion, the area of GGOs is a useful predictor of survival in acute PQ intoxication, especially in patients with low plasma PQ levels.