BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.

Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.

Objective:To improve the understanding of cervical papillary squamous cell carcinoma (PSCC), and to provide evidence for the diagnosis and treatment of PSCC.Methods:The clinicopathological and follow-up data of 18 patients diagnosed PSCC by preoperative cervical biopsy in Tangshan Gongren hospital were collected, the correlation of preoperative biopsy, liquid-based cells, and human papilloma virus (HPV) with postoperative pathology and prognosis was analyzed.Results:The concordance rate between preoperative biopsy and postoperative pathology was 50% (9/18). 4 patients showed the characteristic features of PSCC in their liquid-based cells of the 9 patients who were diagnosed as PSCC postoperatively (4/9), the HPV infection rate was 44.4% (4/9), the International Federation of Gynecology and Obstetrics stage were IA1-IB1, no lymph node metastasis, recurrence or death occurred in all patients.Conclusions:Cervical biopsy before operation has certain limitations in the diagnosis of PSCC, which requires a clear diagnosis by postoperative pathology. The HPV infection rate is lower, the stage is earlier and the prognosis is better in PSCC. Some patients can choose a less invasive surgical method than radical surgery.

Objective:To evaluate the value of visual analysis and standardized uptake value ratio (SUVR) during 18F-florbetapir (AV45) PET/CT brain imaging in diagnosis of β-amyloid (Aβ) deposition in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD), and to explore the clinical ancillary value of the two indexes. Methods:From December 2018 to July 2019, a total of 47 subjects, including 5 (3 males, 2 females, age (58±13) years) normal controls (NC), 8 (2 males, 6 females, age (66±10) years) patients with AD and 34 (16 males, 18 females, age (70±7) years) patients with MCI were enrolled. All subjects underwent 18F-AV45 PET/CT scan. All images were evaluated by visual analysis and SUVR were calculated. The diagnostic efficiencies of visual analysis and SUVR were compared by McNemar test and Kappa test. One-way analysis of variance and Welch test were used to compare data differences. The best threshold value of SUVR was obtained by receiver operating characteristic (ROC) curve analysis. Results:The positive rate of Aβ deposition for all subjects was 46.81%(22/47) by SUVR analysis, and 38.30%(18/47) by visual analysis. There was no significant difference between the two methods ( χ2=33.15, P>0.05), and the consistency was good ( Kappa=0.83). Considering the clinical diagnosis as the"gold standard", the Aβ deposition obtained by visual analysis and SUVR analysis can effectively distinguish AD from NC, and the sensitivities were 7/8 vs 8/8, respectively, both specificities were 5/5( χ2=9.48, P>0.05), with good consistency ( Kappa=0.84). SUVR quantitative analysis could distinguish AD from NC, AD from MCI ( F values: 3.99-8.79, all P<0.01), but could not distinguish NC from MCI (all P>0.05). ROC curve analysis showed that the best threshold value of precuneus′ SUVR was 1.08 for the differential diagnosis of AD and NC; for the differential diagnosis of AD and MCI, the best threshold value of lateral temporal′s SUVR was 1.06. Conclusion:Visual analysis was consistent with SUVR′s qualitative determination during 18F-AV45 PET/CT imaging for brain Aβ deposition, while SUVR quantitative analysis could assist in the differential diagnosis of AD and NC, AD and MCI.

Objective: To investigate the metabolic patterns of ¹¹C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and ¹⁸F-fluorodeoxyglucose (FDG) PET/CT imaging in patients with tremor and non-tremor Parkinson′s disease (PD). Methods: From March 2018 to March 2019, 28 PD patients (19 tremor patients: 14 males and 5 females, age: (59.9±11.4) years; 9 non-tremor patients: 3 males and 6 females, age: (62.6±9.0) years) were enrolled. For the two groups, the ¹¹C-CFT uptake values in caudate nucleus, anterior putamen and posterior putamen as well as ¹⁸F-FDG uptake values in all brain regions were calculated by regions of interest (ROI) method. Two-sample t test or Mann-Whitney u test were used to analyze the data. Results: Caudate nucleus ¹¹C-CFT uptake in PD patients with tremor was higher than that without tremor (3.03±0.51 vs 2.60±0.62; t=2.687, P<0.05). Yet thalamus glucose uptake of non-tremor PD patients showed more active than tremor patients (1.14±0.05 vs 1.10±0.03; t=3.449, P<0.01). Sorted by modified Hoehn-Yahr stage, tremor patients in advanced stage (stage≥2.5) were characterized by glucose uptake increase in the putamen and cerebellum compared with non-tremor advanced group (1.27±0.04 vs 1.21±0.05, 0.94±0.04 vs 0.86±0.08; t values: 2.695 and 2.492, both P<0.05). Metabolic decrease in the premotor areas was observed in tremor patients in advanced stage compared with early stage (1.07±0.02 vs 1.10±0.03; t=2.053, P<0.05). Conclusion ¹¹C-CFT and ¹⁸F-FDG PET/CT imaging can indicate different metabolic patterns between tremor and non-tremor PD, thus providing information for clinical practice and differential diagnosis.

Objective To analyze the correlation between CT characteristics and epidermal growth factor receptor (EGFR)mutations in pulmonary adenocarcinoma.Methods 82 patients (87 lesions)with pulmonary adenocarcinoma were retrospectively collected.All patients were underwent CT examination before operation,and EGFR gene were determined after operation.Results EGFR mutations were found in 44 of 87 lesions (50.57%).The EGFR mutations rate was 50.00% in females and 47.50% in males,there was no statistical difference between genders (P=0.821).The EGFR mutations rate was 46.55% in the right lung and 58.62% in the left lung,while no statistically significant difference was found (P=0.289).Among all the CT characteristics,the mutations rate was 63.89% in spiculated lesions and 60.71% in lesions with pleural indentation,the differences was statistically significant (P<0.05).The mutations rate was 59.25% in lesions containing solid component and 36.36% in pure ground glass opacity lesions,the difference was statistically significant (P=0.011). There were no statistically differences in lobulation,cavitation and lymphadenectasis (P>0.05).The pleural indentation was the highest in sensitivity (77.27%)and negative predictive value (67.74%).The spiculation was the highest in specificity (69.77%)and positive predictive value (63.89%).Conclusion Among all the CT characteristics,pleural indentation,spiculation and the lesion containing solid component are prone to EGFR mutations.

Purpose To detect the expressions of stress induced phosphoprotein 1 (STIP1) and estrogen receptor-α(ER-α) in papil-lary thyroid carcinoma and to analyse the relationship between STIP1 and ER-α. Methods 54 cases of paraffin-embedded tissues of papillary thyroid carcinoma, 18 cases of papillary thyroid carcinoma with lymph node metastasis, 15 cases of Hashimoto’ s thyroiditis, 10 cases of adjacent normal thyroid tissue were collected. The expressions of STIP1 and ER-αwere detected by immunohistochemistry, and the relationship between the expressions and clinicopathological features of papillary thyroid carcinoma was analyzed. Results The expression of STIP1 and ER-α in papillary thyroid cancer group ( 55. 6% and 44. 4%) were higher than that of normal thyroid group (10% and 0) and Hashimoto’s thyroiditis group (8. 3% and 0, all P<0. 05). STIP1 expressions was related to lymph node metastasis ( P<0. 05 ) , while ER-α expression was related to gender, TG-Ab and the merger of nodular goiter, but not related to lymph node metastasis (P>0. 05). The expressions of STIP1 and ER-α in papillary thyroid carcinoma were not related to patients’ age , tumor location, number of tumors, tumer size, invasion of capsule, the concomitant Hashimoto’ s thyroiditis and TPO-Ab ( all P>0. 05). And the expressions of STIP1 was not related to gender, TG-Ab and the merger of nodular goiter (all P>0. 05). A positive correlation was found between the expressions of STIP1 and ER-αin thyroid papillary carcinoma (P<0. 05). Conclusion STIP1 and ER-α in papillary thyroid carcinoma may be related with lymph node metastasis.