Microplastics (MPs) are omnipresent environmental pollutants posing potential impacts on organisms. To explore the transgenerational effects of polystyrene nanoplastics (PS-NPs) and the molecular mechanisms at environmental relevant concentrations, Caenorhabditis elegans (C.elegans) was applied as an in vivo model. Worms were incubated with PS-NPs at environmental concentrations from L1 larvae stage, while subsequent generations (F1 -F3) were maintained under non-exposure condition. Reproductive potential was estimated based on brood size, fertilized eggs, oocytes, and germline apoptosis. Results indicated that PS-NPs induced transgenerational toxicity in inhibiting reproductive ability, impairing gonad development, and promoting germline apoptosis. And these adverse effects were associated with dysregulated expression of apoptosis-related genes. Furthermore, DNA damage was participated in enhancing germline apoptosis through activating DNA damage checkpoint kinase ATL-1 and p53 ortholog CEP-1. Additionally, PS-NPs reduced the expression of DNA recombination repair protein RAD-51 across generations. This study demonstrates that reproductive toxicity evoked by PS-NPs can be transmitted to offspring by inducing DNA damage through activating ATL-1 and CEP-1, while simultaneously inhibiting DNA repair.

IntroductionGastric cancer (GC) is a common malignancy of digestive system with high morbidity and mortality. Cisplatin (CDDP) is often applied in GC clinical treatment, particularly in the postoperative adjuvant chemotherapy, where it improves patient survival and reduces recurrence risk. However, the development of drug resistance following prolonged use poses an obstacle in its clinical use. This study investigated the role of tumor necrosis factor receptor-associated protein 1 (TRAP1) in modulating the sensitivity of GC cells to CDDP through oxidative stress pathway.MethodsBioinformatic analysis was employed to assess TRAP1 expression in GC tissues compared to adjacent normal gastric tissues, and to evaluate its association with patient prognosis. Using lentivirus transfection and RNA interference, GC cell models with TRAP1 overexpression and silencing were established, then reactive oxygen species (ROS), mitochondrial membrane potential (MMP), DNA damage and cell death were measured following treatment with CDDP alone or in combination with antioxidant N-acetyl-L-cysteine (NAC).ResultsResults indicated that TRAP1 was upregulated in GC tissues and elevated TRAP1 was related with poor prognosis. In GC cells exposed to CDDP, TRAP1 reduced ROS, stabilized MMP and mitigated DNA damage, leading to diminished cell death. TRAP1 overexpression potentiated the protective effects of NAC, while TRAP1 silencing counteracted the protective effects.DiscussionThese findings indicated that TRAP1 attenuated CDDP sensitivity in GC cells by reducing cell death caused by CDDP-induced oxidative stress. TRAP1 represented a potential biomarker and a therapeutic target in GC treatment. This study provided a new strategy for improving the efficacy of CDDP-based chemotherapy through individualized treatment approaches.

The therapeutic efficacy of cisplatin in gastric cancer (GC) is frequently constrained by chemoresistance and systemic toxicity. Targeted small molecules hold promise for providing synergistic effects that enhance treatment outcomes. GC cell viability was assessed via a Cell Counting Kit-8 (CCK-8) assay. Apoptosis, intracellular reactive oxygen species (ROS) levels, and the mitochondrial membrane potential were evaluated via flow cytometry and JC-1 staining. Transcriptomic analysis [RNA-sequencing (RNA-Seq)] was subsequently conducted to identify differentially regulated pathways, followed by validation via reverse transcription-quantitative PCR and western blotting. DNA damage was measured by γ-H2AX immunofluorescence, and clonogenic survival was examined. The NOX1-specific inhibitor ML171 was used to verify its mechanistic involvement. Hesperadin markedly suppressed GC cell proliferation in a dose-dependent manner and induced mitochondrial apoptosis by regulating the Bcl-2/Bax ratio and activating caspase pathways. RNA-Seq analysis revealed significant upregulation of NOX1 and activation of oxidative stress-associated pathways following Hesperadin treatment. Cotreatment with Hesperadin and cisplatin markedly reduced the IC50 of cisplatin, increased ROS accumulation, aggravated DNA damage, and potentiated apoptotic cell death. Notably, ML171 attenuated ROS generation and apoptotic effects, confirming the occurrence of a NOX1-dependent mechanism. In conclusion, Hesperadin enhances the sensitivity of GC cells to cisplatin by inducing NOX1-mediated oxidative stress and promoting mitochondrial dysfunction-driven apoptosis, underscoring its potential as an effective combinatorial therapeutic strategy for GC treatment.

The transcription factor MYB proto-oncogene like 2 (MYBL2) has been reported to be involved in the occurrence and development of various tumors, however, its role in gastric cancer (GC) remains to be elucidated. In this study, the Kaplan-Meier plotter was used to evaluate the prognostic value of different MYBL2 expression levels in GC patients. The UALCAN database were applied to analyze the relationships between MYBL2 and clinicopathological characteristics of GC. GC cell proliferation, cell cycle and apoptosis were determined by CCK-8 and flow cytometry assays, and proteins were examined by Western blot analysis. Next, signaling pathway enrichment analysis of MYBL2-related genes and protein expression were analyzed by Gene Set Enrichment Analysis (GSEA) and Western blot assays. The results found that MYBL2 expression was significantly upregulated in GC compared with adjacent non-malignant tissues and associated with poor patient survival, tumor, stages and lymph node metastasis. Forced expression of MYBL2 could promote cell proliferation, resulting in an accelerated S phase progression and inhibiting cell apoptosis in GC cells. Conversely, MYBL2 silencing inhibited cell proliferation, induced G2/M phase arrest and promoted cell apoptosis in GC cells. Mechanistically, Western blot analysis showed that MYBL2 silencing decreased the expression of BCL2 and upregulated the expression of Cleaved-caspase-3 and BAX in HGC-27 cells. Conversely, MYBL2 overexpression in AGS cells resulted in the opposite effects. Furthermore, enforced expression of MYBL2 activated the PI3K/AKT signaling pathway, especially AKT phosphorylation. Additionally, the AKT inhibitor MK2206 significantly reversed the proliferation capacity of GC cells induced by MYBL2 overexpression. Therefore, these results suggest that upregulated expression of MYBL2 contributes to GC cell growth and inhibits cell apoptosis by regulating the PI3K/AKT and BCL2/BAX/Cleaved-caspase-3 signaling pathways in GC cells indicating that MYBL2 may be a new therapeutic target and prognostic marker for GC.

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.

Redox responses modulated by intracellular long noncoding RNA (lncRNA) can be involved in tumorigenesis and progression. However, the role of redox-related lncRNAs (RRlncRNAs) in gastric cancer (GC) development remains mostly unknown. Our research aims to establish and validate novel prognostic and immune infiltration markers for GC by constructing a prognostic model of RRlncRNAs. We downloaded the transcriptomic and mutational data for 407 GC pa-tients from The Cancer Genome Atlas (TCGA) database and randomized them 1:1 into a training and validation set to show that redox-related lncRNAs affect GC patients' prognosis. Subse-quently, the prognostic model was constructed for the screened RRlncRNAs using the Least Absolute Shrinkage and Selection Operator (LASSO) and the multivariate COX regression algo-rithm. Then, Survival analyses were performed on the train and test sets. The overall survival rate of GC patients was significantly correlated with the signatures of eight RRlncRNAs, including AC103702.2, AL138756.1, AL356417.2, CFAP61-AS1, RHPN1-AS1, CDK6-AS1, LINC02864, and AL355574.1. Meanwhile, we validated the model's accuracy through nomograms, Decision Curve Analysis (DCA), and comparisons using models from other studies. The results demonstrated that our model is more effective and outperforms the signature of Jiang et al. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of gene enrichment in high-risk patients shows significant enrichment in immune-related pathways. Waterfall plots of gene mutations, tumor mutation burden (TMB), and tumor immune dysfunction and exclusion (TIDE) showed significant differences in immune function between high- and low-risk groups. Then, we divided the 407 GC patients into two clusters using a consensus clustering algorithm and found significant differences in their immune microenvironment through immune cell difference anal-ysis, ESTIMATEScore, and gene set enrichment analysis (GSEA). Taken together, we conclude that the prognostic model constructed by RRlncRNAs can significantly affect the prognosis of GC patients and may alter their tumor progression by modulating the immune microenvironment in vivo. Our study found eight RRlncRNA-associated signatures, representing promising new markers for immunotherapy and diagnosis in GC patients.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

Abstract The oxidative phosphorylation(OXPHOS) is one of the important activities and plays an important role in the development of tumor. This study combines transcriptome and clinical data from gastric cancer(GC) patients from the GEO and TCGA databases. Consensus Cluster Analysis divides GC patients into OXPHOS-high and -low groups. The GSVA analysis displayed significant differences in the immune microenvironment among the different OXPHOS groups. Furthermore, WGCNA was used to screen immune-related core molecules, and analyzed the differentially-Expressed Genes(DEGs) among different subtypes. AURKB was identified as a key molecule linking oxidative phosphorylation and immunity in GC. Subsequently, the biological functions of AURKB in GC were analyzed using transcriptomics and cell experiments. Finally, the link between AURKB and immunotherapy effect in patients with GC was analyzed in combination with multiple immune-related databases. Our study determined that AURKB is involved in the OXPHOS and affects the response to immunotherapy in GC patients. The combination of AZD1152 and targeted Therapy or immunotherapy may be a promising strategy in the treatment of GC.

目的:分析情境模拟教学融入思政元素在医学遗传学实验课中的应用效果和学生认可度.方法:选取 2021 级临床专业本科生180 名(共6 个实验班),分为对照组(传统实验课教学法)和观察组(情景模拟教学法融入思政元素),各 90 名.比较2 组学生实验成绩分级、医德医风核心维度测评及教学方法对能力提升的认可度.结果:观察组学生的实验课成绩分级优于对照组(P<0.05);观察组在接近临床实际体验、提高学习主动性、提高医患沟通技巧和提高人文关怀的意识方面认可度均明显高于对照组(P<0.01);在同一因变量水平下,观察组医德医风核心维度多元线性回归分析的各维度得分及总分均高于对照组(P<0.05～P<0.01).结论:在医学遗传学实验课中运用情境模拟教学并融入思政元素,有助于提高学生的实验成绩并培养良好的医德医风,且学生对能力提升的认可度较高.

Abnormal N6-methyladenosine (m6A) modification levels caused by METTL3 have been identified to be a critical regulator in human cancers, and its roles in the immune microenvironment and the relationship between targeted therapy and immunotherapy sensitivity in gastric cancer (GC) remain poorly understood. In this study, we assessed the transcriptome-wide m6A methylation profile after METTL3 overexpression by m6A sequencing and RNA sequencing in BGC-823 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to analyze the function of core targets of METTL3. Eighteen methylation core molecules were identified in GC patients by combining transcriptome and methylome sequencing. GC patients can be separated into two subtypes based on the expression of 18 methylation core molecules. Furthermore, subgroup analysis showed that patients with different subtypes had a different OS, PFS, stage, grade, and TMB. Gene set enrichment analysis (GSEA) showed that immune-related pathways were enriched among subtype A. The ESTIMATE analysis suggested that the extent of infiltration of immune cells was different in two subtypes of GC patients. Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA) database also showed that there were significant differences in the efficacy of immunotherapy among different types of GC patients. Altogether, our results reveal that METTL3-mediated m6A methylation modification is associated with the immune microenvironment and the effects of immunotherapy in GC patients. Our findings provide novel insights for clinicians in the diagnosis and optimal treatment of GC patients.

METTL3-mediated RNA N6-methyladenosine (m6A) is the most prevalent modification that participates in tumor initiation and progression via governing the expression of their target genes in cancers. However, its role in tumor cell metabolism remains poorly characterized. In this study, m6A microarray and quantitative proteomics were employed to explore the potential effect and mechanism of METTL3 on the metabolism in GC cells. Our results showed that METTL3 induced significant alterations in the protein and m6A modification profile in GC cells. Gene Ontology (GO) enrichment indicated that down-regulated proteins were significantly enriched in intracellular mitochondrial oxidative phosphorylation (OXPHOS). Moreover, the protein-protein Interaction (PPI) network analysis found that these differentially expressed proteins were significantly associated with OXPHOS. A prognostic model was subsequently constructed based on the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, and the high-risk group exhibited a worse prognosis in GC patients. Meanwhile, Gene Set Enrichment Analysis (GSEA) demonstrated significant enrichment in the energy metabolism signaling pathway. Then, combined with the results of the m6A microarray analysis, the intersection molecules of DEPs and differential methylation genes (DMGs) were significantly correlated with the molecules of OXPHOS. Besides, there were significant differences in prognosis and GSEA enrichment between the two clusters of GC patients classified according to the consensus clustering algorithm. Finally, highly expressed and highly methylated molecules regulated by METTL3 were analyzed and three (AVEN, DAZAP2, DNAJB1) genes were identified to be significantly associated with poor prognosis in GC patients. These results signified that METTL3-regulated DEPs in GC cells were significantly associated with OXPHOS. After combined with m6A microarray analysis, the results suggested that these proteins might be implicated in cell energy metabolism through m6A modifications thus influencing the prognosis of GC patients. Overall, our study revealed that METTL3 is involved in cell metabolism through an m6A-dependent mechanism in GC cells, and indicated a potential biomarker for prognostic prediction in GC.

Objective: Investigate the effects of Hexokinase-3 on the proliferation, cell cycle, migration and immunologic invasion of RKO and HCT116. Methods: The expression levels of HK3 in tumor and normal colon samples were analyzed by bioinformatics. RKO and HCT116 were transfected with the control group (si-NC) and interference group HK3(si-HK3#1, si-HK3#2). CCK-8, Flow cytometry, wound healing and Transwell were used to examine the effects of interference with HK3 on the proliferation, cell cycle and migration of RKO and HCT116 cells. The expression levels of vimentin and E-cadherin, which are related to epithelial-mesenchymal transition(EMT), were detected by Western blot. Results: HK3 is associated with infiltration of multiple immune cells and co-expression with multiple immune checkpoints in colorectal cancer. Compared with the Control group (si-NC),the protein expression level of HK3 in interference group (si-HK3#1, si-HK3#2) was significantly decreased(P<0.05);the proliferation and migration of RKO and HCT116 cells were significantly inhibited(P<0.05);the cell cycle of RKO and HCT116 cells was arrested in S phase(P<0.05) and the expression of E-cadherin protein was increased, but the expression of vimentin protein was inhibited(P<0.05). Conclusion: HK3 affects the level of immunologic invasion of colon cancer. Interference with HK3 inhibits the proliferation, cell cycle and migration of colon cancer cells by inhibiting EMT behavior.

Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.

高校的立身之本在于立德树人.挖掘课程中思政元素,将思政育人融入到专业课教与学活动中,是落实高校思政教育教学改革的关键举措.推进课程思政建设的意义重大、影响深远,传统的高校思想政治教育任务主要由思政课程教师与党团学等部门负担.基于医学生重要基础课程《医学遗传学》,在确保基本知识点讲授的前提下,探索将思想政治教育内容融入专业课程,探讨以课程思想政治教育教学改革为抓手,培养优秀医学后备人才的可行性策略,使专业课程品出"思政味",确保专业课"同向同行、协同育人",并为其它医学院校专业课程思想政治教育提供借鉴.

目的 探索结肠癌对FOLFOX化疗方案耐药的关键机制.方法 综合GEO数据库中FOL-FOX 化疗方案相关数据集,合并后筛选差异表达基因,随机森林树提取特征基 因作为 耐药核心基因,评估其与临床药物的敏感性关系.共识聚类区分耐药核心基因的亚型及亚型的差异基因集,构建基于TCGA和GSE29621数据的风险模型,评估耐药核心基因与患者临床病理特征和预后的联系.结果 随机森林树筛选出来的耐药核心基因的表达水平能明显将对FOLFOX化疗方案反应与否的患者区分开来.分型结果显示主要的耐药原因为免疫浸润,使用耐药相关基因构建的风险模型比常规TNM分期更能预测患者的预后,且高低风险组患者的免疫浸润程度和免疫细胞水平具有明显差异.结论 FOLFOX化疗耐药与结肠癌患者的免疫浸润密切相关,耐药相关基因构建的风险模型能较好预测患者的临床病理转归和预后.

Graphene oxide (GO) exposure may cause damage to C. elegans. However, the role of autophagy and its interactive effect with oxidative response in GO toxicity still remain largely unclear. In the present study, we investigated the protective role of autophagy against GO and its association with oxidative response using C. elegans as an in vivo system. Results indicated that GO exposure induced autophagy in a dose dependent manner in C. elegans. Autophagy inhibitor 3-methyladenine (3-MA) and silencing autophagy genes lgg-1, bec-1 and unc-51 exacerbated the toxicity of GO whereas autophagy activator rapamycin alleviated it. In addition, the antioxidant N-Acetyl-L-cysteine (NAC) effectively suppressed the toxicity of GO with increased resistance to oxidative stress. Worms with RNAi-induced antioxidative genes sod-1, sod-2, sod-3 and sod-4 knockdown were more sensitive to GO. 3-MA increased the expression of superoxide dismutase SOD-3 under GO exposure conditions and exacerbated the toxicity of GO under the anti-oxidation inaction condition by sod-3 RNAi. In contrast, NAC reduced autophagy levels in GO exposed nematodes and increased tolerance to GO in autophagy-defective worms. These results suggested that autophagy and antioxidative response provide complementary protection against GO in C. elegans.

Objective: m7G is a post-transcriptional modification modality, however, limited research has been conducted on its role in colon cancer. DNA damage repair (DDR) is an important factor that contributes to colon cancer development, growth and chemoresistance. This study aimed to explore whether m7G-related DNA damage repair genes may be used as biomarkers to predict the prognosis of colon cancer patients. Methods: We use non-negative matrix factorization (NMF) to type CRC patients into. Risk models were constructed using different expression genes in two clusters. We assessed the reliability of risk models with DCA curves, and a Nomogram. Meanwhile, The receiver operating characteristic and C-index curves were used to compare the predictive significance of the constructed risk models with other studies. In additional, we examined the significance of risk models on patients' immunity microenvironment and response to immune therapy. Finally, we used a series of cellular experiments to validate the effect of model genes on the malignant progression of CRC cells. Results: Twenty-eight m7G genes were obtained from the GSEA database. Multivariate Cox and LASSO Cox regression analysis was performed and eleven m7G-related DDR genes were identified for constructing the risk model. Survival and stage of CRC patients were worser in the high-risk group than in the low-risk group for both the training and test sets. Additionally, the different immune microenvironment status of patients in the high- and low-risk groups, suggesting that patients in the low-risk group may be more sensitive to immunotherapy, particularly immune checkpoint inhibitors. Finally, we found that depletion of ATP2A1, one of the risk genes in our model, influence the biologic behaviour of CRC cells significantly. Conclusion: The m7G-related DDR genes can be used as important markers for predicting patient prognosis and immunotherapy response. Our data suggest that ATP2A1 may promote the proliferation of colon cancer cells. These findings may provide new therapeutic targets for the treatment of colon cancer.

OBJECTIVE:To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).METHODS:We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.RESULTS:We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.CONCLUSION:The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.

Objective DNA damage response (DDR) is a complex system that maintains genetic integrity and the stable replication and transmission of genetic material. m6A modifies DDR-related gene expression and affects the balance of DNA damage response in tumor cells. In this study, a risk model based on m6A-modified DDR-related gene was established to evaluate its role in patients with gastric cancer. Methods We downloaded 639 DNA damage response genes from the Gene Set Enrichment Analysis (GSEA) database and constructed risk score models using typed differential genes. We used Kaplan-Meier curves and risk curves to verify the clinical relevance of the model, which was then validated with the univariate and multifactorial Cox analysis, ROC, C-index, and nomogram, and finally this model was used to evaluate the correlation of the risk score model with immune microenvironment, microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoints. Results In this study, 337 samples in The Cancer Genome Atlas (TCGA) database were used as training set to construct a DDR-related gene model, and GSE84437 was used as external data set for verification. We found that the prognosis and immunotherapy effect of gastric cancer patients in the low-risk group were significantly better than those in the high-risk group. Conclusion We screened eight DDR-related genes (ZBTB7A, POLQ, CHEK1, NPDC1, RAMP1, AXIN2, SFRP2, and APOD) to establish a risk model, which can predict the prognosis of gastric cancer patients and guide the clinical implementation of immunotherapy.