1.Retrospective analysis of the predictive value of immunoglobulin and complement combined leukocyte levels on the outcome of severe COVID-19
Yong ZHAO ; Weirong ZENG ; Fuan YU ; Youtao HU ; Li XU ; Junfeng ZENG ; Kunyun JIA ; Jianbin SUN ; Jiancheng TU
Chinese Journal of Experimental and Clinical Virology 2021;35(1):1-6
Objective:To retrospectively analyze the blood leukocytes (WBC), lymphocytes (LYM), lymphocyte% (LYM%), and serum total immunoglobulin (IGA, IGG, IGM) and complement (C3, C4) index levels to explore its predictive value for the outcome of COVID-19 severe pneumonia.Methods:Eighty-five COVID-19 patients with severe pneumonia diagnosed in our hospital were randomly selected and were divided into good outcome group (50 cases) and poor outcome group (35 cases). WBC, LYM, LYM%, IGA, IGG, IGM, and C3, C4 level data, and analyze the differences between the two groups, the correlation of each indicator, and ROC curves of single and joint detection to explore relationship between indicators and outcomes, and the predictive efficacy of indicators on outcomes.Results:Differences in WBC, LYM, LYM%, IGG, and IGA levels were significant between the two groups ( P=0.000, 0.015, 0.000, 0.000, 0.001), among them with significant differences, LYM and LYM% were significantly positively correlated ( r=0.669, P=0.000), while WBC and LYM% levels were significantly negatively correlated ( r=-0.600, P=0.000), WBC and IGA levels were significantly positively correlated ( r=0.283, P=0.009) and IGG and IGA levels were also significantly positively correlated ( r=0.0.442, P=0.000); After logistic regression analysis, WBC, LYM, LYM%, IGG, and IGA are all important influencing factors ( P=0.001, 0.022, 0.000, 0.000, 0.003); but only the levels of WBC, IGG, and LYM% are Independent risk factors ( P=0.034, 0.004, 0.001), the ROC curve of the single detection and joint detection of their predicted outcome performance, respectively, and the max AUC (AUC=0.890, P=0.000) at the time of joint testing of WBC, LYM% and IGG, index YI=0.657, it has the greatest predictive power for adverse outcomes, with a sensitivity of 77.10% and a specificity of 88.00%. IGM, C3, C4, IGG/IGM, and C3/C4 levels were not significantly different( P=0.066, 0.204, 0.076, 0.310, 0.156). Conclusions:The levels of WBC, LYM, LYM%, IGG, and IGA in the early admission of COVID-19 infected patients with severe pneumonia have important predictive value for the outcome of them. WBC, LYM% and IGG levels are independent risks and joint detection of the three indexes have the best predictive performance.
2.Expression of MiRNA-221 in Non-small Cell Lung Cancer Tissues and Correlation with Prognosis
LV JUNJIE ; XU LEI ; XU YOUTAO ; QIU MANTANG ; YANG XIN ; WANG JIE ; YIN RONG ; XU LIN
Chinese Journal of Lung Cancer 2014;(3):221-225
Background and objective MicroRNAs were important regulators of tumors and the expression of miRNA-221 was associated with malignant proliferation and invasion in many tumors. hTe aim of this study is to explore the expression of miRNA-221 in non-small cell lung cancer (NSCLC) tissues and its correlation with prognosis. Methods We ret-rospectively analyzed the clinical characteristics of 117 NSCLC patients who underwent surgery in our hospital from Novem-ber 2005 to January 2007. Real-time PCR was used to detect the expression of miRNA-221. Chi-square test was utilized to ana-lyze the relationship between miRNA-221 expression and clinicopathologic features. Survival curves were plotted by using the Kaplan-Meier method and compared by the Log-rank test. A Cox proportional hazard regression model was applied to examine the joint effect of covariants. A P-value less than 0.05 was evaluated as statistically signiifcant. Results hTe patients were di-vided into two groups according to the relatively expression of miRNA-221. No statistically signiifcance was observed between the expression of miRNA-221 and the clinicopathologic parameters, including gender (χ2=0.070, P=0.791), histology (χ2=0.414, P=0.520), p-TNM stage (χ2=0.068, P=0.794) and history of smoking (χ2=0.206, P=0.650). Kaplan-Meier analysis showed that high expression of miRNA-221 was closely associated with a shorter survival time (P<0.001). Finally, both univariate and multivariate analyses demonstrated that high miRNA-221 expression might be a poor prognostic marker of NSCLC patients. Conclusion Our results indicated that down-regulation of miRNA-221 was associated with poor prognosis of patients with NSCLC. MiRNA-221 may serve as a molecular prognosis marker for patients with NSCLC.
3.Clinical Signifcance of Mutant P53 Protein Expression in Lung Adenocarcinoma
BIAN CHUN’AN ; LI ZHONGYOU ; XU YOUTAO ; WANG JIE ; XU LIN ; SHEN HONGBING
Chinese Journal of Lung Cancer 2015;(1):23-28
Background and objective P53 is a tumor protein that acts as a tumor suppressor. Te mutation of P53 may cause loss of tumor suppressor functions and gain of functions favoring cellular proliferation and apoptosis inhibition. Te clinical implications of the tumor protein P53 gene (TP53) mutation in lung adenocarcinoma are indefinite. Te aim of this study is to explore the clinical significance of the mutant P53 protein expression in lung adenocarcinoma tissues. Methods Te clinicopathological data of 120 lung adenocarcinoma patients who underwent surgery were retrospectively analyzed. Te mu-tant P53 protein expression was detected using the immunohistochemical method. Furthermore, the relationship between the mutant P53 expression and the clinicopathological parameters was analyzed using the Chi-square test, whereas that between the mutant P53 expression and overall survival was estimated using the Kaplan-Meier method and Cox regression model. Re-sults Te mutant P53 protein expression rate was 63.3%. Accordingly, the mutant P53 expression was significantly associated with tumor size (P=0.041) and clinicopathological stage (P=0.025). On the one hand, a univariate survival analysis showed that tumor size (P=0.031), lymph node metastasis (P<0.001), clinicopathological stage (P<0.001), and mutant P53 expression (P=0.038) were associated with overall survival. On the other hand, a multivariate survival analysis showed that lymph node metastasis (P=0.014) was an independent poor prognostic factor for overall survival. Conclusion Patients with lung adeno-carcinoma with mutant TP53 had a poor outcome. Accordingly, the mutant P53 protein may serve as a molecular prognosis marker for lung adenocarcinoma patients.
4.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
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.
Humans
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Lung Neoplasms/genetics*
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Adenocarcinoma of Lung/genetics*
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China
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Prognosis
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Transcription Factors