Development and validation of radiology-clinical statistical and machine learning model for stroke-associated pneumonia after first intracerebral haemorrhage.

BACKGROUND: Society is burdened with stroke-associated pneumonia (SAP) after intracerebral haemorrhage (ICH). Cerebral small vessel disease (CSVD) complicates clinical manifestations of stroke. In this study, we redefined the CSVD burden score and incorporated it into a novel radiological-clinical prediction model for SAP. MATERIALS AND METHODS: A total of 1278 patients admitted to a tertiary hospital between 1 January 2010 and 31 December 2019 were included. The participants were divided into training and testing groups using fivefold cross-validation method. Four models, two traditional statistical models (logistic regression and ISAN) and two machine learning models (random forest and support vector machine), were established and evaluated. The outcomes and baseline characteristics were compared between the SAP and non-SAP groups. RESULTS: Among the of 1278 patients, 281(22.0%) developed SAP after their first ICH. Multivariate analysis revealed that the logistic regression (LR) model was superior in predicting SAP in both the training and testing groups. Independent predictors of SAP after ICH included total CSVD burden score (OR, 1.29; 95% CI, 1.03-1.54), haematoma extension into ventricle (OR, 2.28; 95% CI, 1.87-3.31), haematoma with multilobar involvement (OR, 2.14; 95% CI, 1.44-3.18), transpharyngeal intubation operation (OR, 3.89; 95% CI, 2.7-5.62), admission NIHSS score ≥ 10 (OR, 2.06; 95% CI, 1.42-3.01), male sex (OR, 1.69; 95% CI, 1.16-2.52), and age ≥ 67 (OR, 2.24; 95% CI, 1.56-3.22). The patients in the SAP group had worse outcomes than those in the non-SAP group. CONCLUSION: This study established a clinically combined imaging model for predicting stroke-associated pneumonia and demonstrated superior performance compared with the existing ISAN model. Given the poor outcomes observed in patients with SAP, the use of individualised predictive nomograms is vital in clinical practice.

Metabolomic insights into pulmonary fibrosis: a mendelian randomization study.

BACKGROUND: This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets. METHODS: Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences. RESULTS: The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis. CONCLUSIONS: The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis.

Assembly and comparative analysis of the initial complete mitochondrial genome of Primulina hunanensis (Gesneriaceae): a cave-dwelling endangered plant.

BACKGROUND: Primulina hunanensis, a troglobitic plant within the Primulina genus of Gesneriaceae family, exhibits robust resilience to arid conditions and holds great horticultural potential as an ornamental plant. The work of chloroplast genome (cpDNA) has been recently accomplished, however, the mitochondrial genome (mtDNA) that is crucial for plant evolution has not been reported. RESULTS: In this study, we sequenced and assembled the P. hunanensis complete mtDNA, and elucidated its evolutionary and phylogenetic relationships. The assembled mtDNA spans 575,242 bp with 43.54% GC content, encompassing 60 genes, including 37 protein-coding genes (PCGs), 20 tRNA genes, and 3 rRNA genes. Notably, high number of repetitive sequences in the mtDNA and substantial sequence translocation from chloroplasts to mitochondria were observed. To determine the evolutionary and taxonomic positioning of P. hunanensis, a phylogenetic tree was constructed using mitochondrial PCGs from P. hunanensis and 32 other taxa. Furthermore, an exploration of PCGs relative synonymous codon usage, identification of RNA editing events, and an investigation of collinearity with closely related species were conducted. CONCLUSIONS: This study reports the initial assembly and annotation of P. hunanensis mtDNA, contributing to the limited mtDNA repository for Gesneriaceae plants and advancing our understanding of their evolution for improved utilization and conservation.

Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis.

BACKGROUND: Obesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP. METHOD: The body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test. RESULTS: Patients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678-0.784. CONCLUSIONS: This study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.

Non-Invasive Diagnosis of Prostate Cancer and High-Grade Prostate Cancer Using Multiparametric Ultrasonography and Serological Examination.

OBJECTIVES: This study aimed to assess the efficacy of multiparametric ultrasonography (mpUS) combined with serological examination, as a non-invasive method, in detecting prostate cancer (PCa) or high-grade prostate cancer (HGPCa) respectively. METHODS: A cohort of 245 individuals with clinically suspected PCa were enrolled. All subjects underwent a comprehensive evaluation, including basic data collection, serological testing, mpUS and prostate biopsy. Random Forest (RF) models were developed, and the mean area under the curve (AUC) in 100 cross-validations was used to assess the performance in distinguishing PCa from HGPCa. RESULTS: mpUS features showed significant differences (p < 0.001) between the PCa and non-PCa groups, as well as between the HGPCa and low-grade prostate cancer (LGPCa) groups including prostate-specific antigen density (PSAD), transrectal real-time elastography (TRTE) and intensity difference (ID). The RF model, based on these features, demonstrated an excellent discriminative ability for PCa with a mean area under the curve (AUC) of 0.896. Additionally, another model incorporating free prostate-specific antigen (FPSA) and color Doppler flow imaging (CDFI) achieved a high accuracy in predicting HGPCa with a mean AUC of 0.830. The nomogram derived from these models exhibited excellent individualized prediction of PCa and HGPCa. CONCLUSION: The RF models incorporating mpUS and serological variables achieved satisfactory accuracies in predicting PCa and HGPCa.

Prediction of Multimorbidity in Brazil: Latest Fifth of a Century Population Study.

BACKGROUND: Multimorbidity is characterized by the co-occurrence of 2 or more chronic diseases and has been a focus of the health care sector and health policy makers due to its severe adverse effects. OBJECTIVE: This paper aims to use the latest 2 decades of national health data in Brazil to analyze the effects of demographic factors and predict the impact of various risk factors on multimorbidity. METHODS: Data analysis methods include descriptive analysis, logistic regression, and nomogram prediction. The study makes use of a set of national cross-sectional data with a sample size of 877,032. The study used data from 1998, 2003, and 2008 from the Brazilian National Household Sample Survey, and from 2013 and 2019 from the Brazilian National Health Survey. We developed a logistic regression model to assess the influence of risk factors on multimorbidity and predict the influence of the key risk factors in the future, based on the prevalence of multimorbidity in Brazil. RESULTS: Overall, females were 1.7 times more likely to experience multimorbidity than males (odds ratio [OR] 1.72, 95% CI 1.69-1.74). The prevalence of multimorbidity among unemployed individuals was 1.5 times that of employed individuals (OR 1.51, 95% CI 1.49-1.53). Multimorbidity prevalence increased significantly with age. People over 60 years of age were about 20 times more likely to have multiple chronic diseases than those between 18 and 29 years of age (OR 19.6, 95% CI 19.15-20.07). The prevalence of multimorbidity in illiterate individuals was 1.2 times that in literate ones (OR 1.26, 95% CI 1.24-1.28). The subjective well-being of seniors without multimorbidity was 15 times that among people with multimorbidity (OR 15.29, 95% CI 14.97-15.63). Adults with multimorbidity were more than 1.5 times more likely to be hospitalized than those without (OR 1.53, 95% CI 1.50-1.56) and 1.9 times more likely need medical care (OR 1.94, 95% CI 1.91-1.97). These patterns were similar in all 5 cohort studies and remained stable for over 21 years. A nomogram model was used to predict multimorbidity prevalence under the influence of various risk factors. The prediction results were consistent with the effects of logistic regression; older age and poorer participant well-being had the strongest correlation with multimorbidity. CONCLUSIONS: Our study shows that multimorbidity prevalence varied little in the past 2 decades but varies widely across social groups. Identifying populations with higher rates of multimorbidity prevalence may improve policy making around multimorbidity prevention and management. The Brazilian government can create public health policies targeting these groups, and provide more medical treatment and health services to support and protect the multimorbidity population.

Transcriptome mapping of renal clear cell carcinoma revealed by machine learning algorithm based on enhanced computed tomography images.

BACKGROUND: A growing number of studies have shown that inflammation-related components of the tumor microenvironment (TME) affect the clinical outcomes of cancer patients, and advances in radiomics may help predict survival and prognosis. METHODS: We performed a systematic analysis of inflammation-related genes (IRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and mapped their interaction network to assess the specific relationship between these differentially expressed inflammation-related genes (DEIRGs) and inflammation. The association between DEIRGs and prognosis was discussed and further validated using consensus cluster analysis. Next, we constructed IRGs-related risk score from the collected information and validated the prognostic value of the model using Kaplan-Meier survival analysis and receiver operating characteristic analysis. Computed tomographic images corresponding to the TCGA-ccRCC cohort were obtained from the Cancer Imaging Archive database for radiomics signature extraction. RESULTS: We screened for prognostic IRGs and found that they were positively correlated with inflammatory cells in the tumor microenvironment associated with tumor progression and metastasis, such as activated CD8+ cells, myeloid-derived suppressor cells and neutrophils. The impact of IRGs on the prognosis of ccRCC patients was also verified. Using these differentially expressed genes, we successfully constructed a risk signature and validated its good prognosis assessment for patients. Furthermore, radiomics-based prognostic models performed better than those using risk signatures or clinical characteristics. CONCLUSIONS: IRG-related risk scores play an important role in assessing the prognosis and improving the management of patients with ccRCC. Through this feature, the infiltration of immune cells in the TME can be predicted. Furthermore, non-invasive radiomics signatures showed satisfactory performance in predicting ccRCC prognosis.

Prognostic value of genomic mutations in metastatic prostate cancer.

Metastatic prostate cancer (mPC) has a poor prognosis, and new treatment strategies are currently being offered for patients in clinical practice, but mPC is still incurable. A considerable proportion of patients with mPC harbor homologous recombination repair (HRR) mutations, which may be more sensitive to poly (ADP-ribose) polymerase inhibitors (PARPis). We retrospectively included genomic and clinical data from 147 patients with mPC from a single clinical center, with a total of 102 circulating tumor DNA (ctDNA) samples and 60 tissue samples. The frequency of genomic mutations was analyzed and compared with that in Western cohorts. Cox analysis was used to assess progression-free survival (PFS) and prognostic factors related to prostate-specific antigen (PSA) after standard systemic therapy for mPC. The most frequently mutated gene in the HRR pathway was CDK12 (18.3%), followed by ATM (13.7%) and BRCA2 (13.0%). The remaining common ones were TP53 (31.3%), PTEN (12.2%), and PIK3CA (11.5%). The frequency of BRCA2 mutation was close to that of the SU2C-PCF cohort (13.3%), but the frequency of CDK12, ATM, and PIK3CA mutations was significantly higher than that in the SU2C-PCF cohort: 4.7%, 7.3%, and 5.3%, respectively. CDK12 mutation were less responsive to androgen receptor signaling inhibitors (ARSIs), docetaxel, and PARPi. BRCA2 mutation helps predict PARPi efficacy. Additionally, androgen receptor (AR)-amplified patients do not respond well to ARSIs, and PTEN mutation are associated with poorer docetaxel response. These findings support the genetic profiling of patients with mPC after diagnosis to guide treatment stratification to customize personalized treatment.

The impact of food restriction on liver enzyme levels: a systematic review and meta-analysis.

CONTEXT: The relationship between food restriction (FR) and liver enzyme levels, such as alanine transferase (ALT), aspartate transferase (AST), and γ-glutamyl transferase (GGT), has not yet been confirmed. OBJECTIVE: A meta-analysis of research articles was conducted to investigate the association of FR and liver enzyme levels. DATA SOURCES: The PubMed, Web of Science, Embase, and Cochrane Library databases were screened for articles published up to April 30, 2022. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement methodology was used to search for research articles. Publication bias was detected using Begg's test. Finally, 17 trials involving 1982 participants and that reported mean value, mean difference, and standard deviation were identified. DATA ANALYSIS: Data were described as the weighted mean difference of body mass index, body weight, and standardized mean difference (SMD) of ALT, AST, and GGT. A reduction in ALT level was observed after a FR intervention (total SMD, -0.36, 95% confidence interval [CI], -0.68 to -0.05). GGT levels also were decreased in 4 studies (total SMD, -0.23; 95%CI, -0.33 to -0.14). According to subgroup analysis, serum AST levels decreased in the medium-term (between 5 wk and 6 mo) group (subtotal SMD, -0.48; 95%CI, -0.69 to -0.28). CONCLUSION: Existing evidence suggests that dietary restriction improves adult liver enzyme levels. The long-term maintenance of healthy liver enzyme levels, particularly in real-world applications, necessitates additional consideration.

Status of 18F-PSMA-1007-PET/CT compared with multiparametric MRI in preoperative evaluation of prostate cancer.

PURPOSE: Treatment of primary prostate cancer extremely depends on preoperative stage. The role of 18F-1007-PSMA-PET/CT in preoperative staging has not been well defined. Our aim was to compare the diagnostic performance of 18F-1007-PEMA-PET/CT, mpMRI, and mpMRI + PEMA-PET/CT in local progression and lymph node invasion of prostate cancer using histopathology as the gold standard. MATERIALS AND METHODS: In this retrospective study, all patients with prostate cancer who underwent mpMRI and 18F-PSMA-1007-PET/CT before operation were included. The role of preoperative imaging was evaluated by predicting the sensitivity and specificity of EPE (extraprostatic extension), SVI (seminal vesicle invasion), and lymph node invasion results. RESULTS: Ultimately, 130 patients were included in this study. In the preoperative judgment of EPE and SVI, mpMRI + PSMA-PET/CT had higher sensitivity and specificity. When predicting lymph node metastasis, PSMA-PET/CT was the best choice. The accuracy of mpMRI + PSMA-PET/CT and PSMA-PET/CT in the T and N stages, respectively, was affected by the least factors. CONCLUSIONS: Based on the combined results of mpMRI and 18F-1007-PSMA-PET/CT, the accuracy of the preoperative judgment of prostatic capsule invasion can be improved, which may be conducive to developing intra-fascial technology while ensuring no tumor-touch isolation. PSMA-PET/CT has the advantages over mpMRI alone in terms of lymph node positivity. Compared with PSMA-PET/CT alone, the combined results can improve the sensitivity, but reduce specificity. Therefore, it is recommended to focus on PSMA-PET/CT to decide whether lymph node dissection should be performed.

Alien species revises systematic status: integrative species delimitation of two similar taxa of Symbrenthia Hübner, [1819] (Lepidoptera, Nymphalidae).

Introduction of organisms to new range may impose detrimental effects on local organisms, especially when closely related species are involved. Species delimitation employing an integrative taxonomy approach may provide a quick assessment for the species status between taxa of interest, and to infer ecological competition and/or introgression that may be associated with the introduction. A nymphalid butterfly, Symbrenthia lilaea lunica, was recently introduced to Taiwan, where a closely related local taxon, S. l. formosanus, can be found. We employed multiple species delimitation methods to study the species status between the two taxa, and the results revealed that they can be recognized as two distinct species, revised to S. l. lilaea (syn. nov.) and S. formosanus (stat. rev.) respectively. We further performed a niche modeling approach to investigate the ecological interaction between the two species. The taxonomic status of the two taxa, now elevated to species, has been revised and conservation facing rapid expansion of the introduced species discussed.

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.

Preparation and identification of isoquinoline alkaloids with ATP citrate lyase inhibitory activity from Dactylicapnos scandens.

Three new isoquinoline alkaloids including a morphine derivative (1), two aporphine alkaloids (2-3), together with five known alkaloids (4-8) were obtained from the extract of Dactylicapnos scandens (D.Don) Hutch. (D. scandens). Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-8 were evaluated for ATP Citrate Lyase (ACLY) inhibitory activity through an enzymatic assay. Among them, 2 and 3 showed the high ACLY inhibitory activity with an IC50 value of 10.48 ± 1.59 and 10.89 ± 4.89 µM.

FTX271: A potential gene resource for plant antiviral transgenic breeding.

Flammutoxin (FTX), as well as its precursor TDP, is a protein from Flammulina velutipes with antiviral activity. Transgenic tobacco with the FTX271 (gene of FTX or TDP) can not only delay the onset time of symptoms but also alleviate the symptoms caused by tobacco mosaic virus (TMV), but the mechanism is still unclear. In this study, FTX271 was introduced into Nicotiana benthamiana, and the disease resistance mechanism activated by FTX271 was speculated by transcriptomic and proteomic techniques. The results showed that TDP was detected, and some genes, proteins and pathways were significant upregulated or enriched in transgenic tobacco, including the mitogen-activated protein kinase (MAPK) cascade signal transduction pathway, the expression of hypersensitive response (HR) marker genes H1N1 and HSR203J, pathogenesis-related (PR) genes, and the key genes COI1 and lipoxygenase gene LOX2 of the jasmonic acid (JA) signaling pathway, indicating FTX271 may activate the MAPK pathway and increase the content of reactive oxygen species (ROS) and JA, which promoted the HR and inducible systemic resistance (ISR). ISR caused increased expression of peroxidase (POD) and other proteins involved in pathogen defense. In addition, transgenic tobacco may use sHSP-assisted photoreparation to alleviate the symptoms of TMV. In conclusion, JA-mediated ISR and sHSP-assisted photoreparation are activated by FTX271 to protect tobacco from TMV infection and alleviate the symptoms caused by the virus. The study provided a theoretical basis for the TMV resistance mechanism of FTX271, which may represent a potential gene resource for plant antiviral transgenic breeding.

Role of moesin and its phosphorylation in VE-cadherin expression and distribution in endothelial adherens junctions.

BACKGROUND AND AIM: Vascular endothelial cadherin (VE-cadherin) is an important element of adherens junctions (AJs) between endothelial cells. Its expression and proper distribution are critical for AJ formation and vascular integrity. Our previous studies have demonstrated that moesin phosphorylation mediated the hyper-permeability in endothelial monolayer and microvessels. However, the role of moesin and its phosphorylation in VE-cadherin expression and distribution is not clear. METHODS AND RESULTS: In vivo, expression of VE-cadherin was significantly reduced in retina and other various tissues in moesin knock out mice (Msn-/Y). In vitro, by regulating moesin expression with siRNA and adenovirus transfection, we verified that moesin has an effect on VE-cadherin expression in HUVECs, while transcription factor KLF4 may participate in this process. In addition, treatment of advanced glycation end products (AGEs) induced abnormal distribution of VE-cadherin in retinal microvessels from C57BL/6 wild type mice, and in vitro studies indicated that moesin Thr558 phosphorylation had a critical role in AGE-induced VE-cadherin internalization from cytomembrane to cytoplasm. Further investigation demonstrated that the inhibition of F-actin polymerization with cytochalasin D could abolish AGE- and Thr558 phosphor-moesin-mediated VE-cadherin internalization. CONCLUSION: This study suggests that moesin regulates VE-cadherin expression through KLF4 and the state of moesin phosphorylation at Thr558 affects the integrity of VE-cadherin-based AJs. Thr558 phosphor-moesin mediates AGE-induced VE-cadherin internalization through cytoskeleton reassembling.

Advanced glycation endproducts mediate chronic kidney injury with characteristic patterns in different stages.

Advanced glycation endproducts (AGEs) have been confirmed to play a causative role in the development of diabetic nephropathy (DN). In this study, we revealed that AGE-induced kidney injury with characteristic patterns in different stages and moesin phosphorylation plays a role in these processes. In WT mice treated with AGE-modified bovine serum albumin (AGE-BSA), distinct abnormal angiogenesis in Bowman's capsule of the kidney emerged early after 1 m under AGE-BSA stimulation, while these neovessels became rare after 6 m. AGE-BSA also induced glomerular hypertrophy and mesangial expansion at 1 m but glomerular atrophy and fibrosis at 6 m. Electron microscopy imaging demonstrated the damage of foot process integrity in podocytes and the uneven thickening of the glomerular basement membrane in the AGE-BSA-treated group, which was more significant after 6 m of AGE-BSA treatment than 1 m. The kidney dysfunction appeared along with these AGE-induced morphological changes. However, these AGE-BSA-induced pathological changes were significantly attenuated in RAGE-knockout mice. Moreover, moesin phosphorylation was accompanied by AGE-BSA-induced alterations and moesin deficiency in mice attenuated by AGE-BSA-induced fibrosis. The investigation on glomerular endothelial cells (GECs) also confirmed that the phosphorylation of moesin T558 is critical in AGE-induced tube formation. Overall, this study suggests that AGEs mediate kidney injury with characteristic patterns by binding with RAGE and inducing moesin phosphorylation.

The DDR-related gene signature with cell cycle checkpoint function predicts prognosis, immune activity, and chemoradiotherapy response in lung adenocarcinoma.

BACKGROUND: As a DNA surveillance mechanism, cell cycle checkpoint has recently been discovered to be closely associated with lung adenocarcinoma (LUAD) prognosis. It is also an essential link in the process of DNA damage repair (DDR) that confers resistance to radiotherapy. Whether genes that have both functions play a more crucial role in LUAD prognosis remains unclear. METHODS: In this study, DDR-related genes with cell cycle checkpoint function (DCGs) were selected to investigate their effects on the prognosis of LUAD. The TCGA-LUAD cohort and two GEO external validation cohorts (GSE31210 and GSE42171) were performed to construct a prognosis model based on the least absolute shrinkage and selection operator (LASSO) regression. Patients were divided into high-risk and low-risk groups based on the model. Subsequently, the multivariate COX regression was used to construct a prognostic nomogram. The ssGSEA, CIBERSORT algorithm, TIMER tool, CMap database, and IC50 of chemotherapeutic agents were used to analyze immune activity and responsiveness to chemoradiotherapy. RESULTS: 4 DCGs were selected as prognostic signatures, and patients in the high-risk group had a lower overall survival (OS). The lower infiltration levels of immune cells and the higher expression levels of immune checkpoints appeared in the high-risk group. The damage repair pathways were upregulated, and chemotherapeutic agent sensitivity was poor in the high-risk group. CONCLUSIONS: The 4-DCGs signature prognosis model we constructed could predict the survival rate, immune activity, and chemoradiotherapy responsiveness of LUAD patients.