Elucidating the molecular distinctions between invasive and non-invasive forms of lung adenocarcinoma is essential for the development of personalized therapeutic approaches and the optimization of patient outcomes. Transfer RNA-derived small RNAs (tsRNAs) have been recognized as pivotal regulators in oncogenic processes. In this study, we identified a specific tsRNA associated with non-invasive lung adenocarcinoma and demonstrated its suppressive effects on cellular proliferation and metastatic potential. At the molecular level, this tsRNA exerts its regulatory function by targeting and repressing G6PD mRNA, thereby perturbing the equilibrium between NADPH and reactive oxygen species (ROS) production. This discovery positions the identified tsRNA as a promising candidate for therapeutic intervention in non-invasive lung adenocarcinoma. Further investigation into the role of tsRNAs in lung adenocarcinoma is imperative to fully harness their potential in clinical management.

The aim of the study was to explore the role of the E3 ubiquitin ligase MARCH7 in the development of non-small-cell lung cancer (NSCLC) and to explore the underlying molecular mechanism.Western blot and immunohistochemistry results showed that the expression of MARCH7 in NSCLC cancer tissues was higher than that in paracancerous tissues. Tissue microarray staining results and clinicopathological parameters of NSCLC patients revealed that MARCH7 expression was closely related to TNM stage, degree of tumor differentiation and lymph node metastasis of NSCLC patients. Furthermore, univariate and multivariate analyses and survival curve analysis showed that high expression of MARCH7 was associated with poor prognosis.In vitro, siRNA was constructed and transfected into A549 cells to inhibit the expression of MARCH7. The CCK-8 assay indicated that the growth rate of tumor cells in the interference group was reduced. The number of colonies and cells in the interference group decreased in the plate clone formation experiment. Flow cytometry showed that G0/G1 phase cells were predominantly increased after blocking endogenous MARCH7 expression, and G0/G1 phase arrest occurred in A549 cells. The reporter gene activity of the NF-κB signaling pathway and Wnt/β-catenin signaling pathway was reduced, as validated by a double luciferase reporter gene assay. Western blot analysis showed that the expression of NF-κB P50, NF-κB P65 and β-catenin was decreased, while the expression of E-cadherin was elevated.In vivo, MARCH7-overexpressing virus was constructed and transfected into A549 cells and then subcutaneously injected into nude mice. It was demonstrated that the tumor volume was significantly larger in the MARCH7 overexpression group than in the control nude mice during the same period. Elevated expression of PCNA and Ki-67 was observed in the tumor mass of the MARCH7 overexpression group, as measured by immunohistochemical analysis, accompanied by enhanced levels of NF-κB P50, NF-κB P65 and β-catenin, as detected by Western blot. These results provide a new idea for the experimental basis for the treatment of NSCLC in the future.

e16039 Background: About half of the newly diagnosed esophageal cancer (EC) cases worldwide occur in China each year. The distribution of EC patients (pts) in China shows a significant regional concentration. Most advanced or metastatic EC pts receive treatment at nearby hospital rather than national or provincial medical centers. Since the approval of PD-1 inhibitors for the treatment of advanced EC in 2022, immunotherapy has become a common treatment for advanced EC. This study aimed to focus on the patient characteristics and treatment pattern of EC pts treated in the hospitals from county or prefecture-level cities in the era of immunotherapy. Methods: This retrospective observational study utilized electronic health records data of pts with advanced/metastatic EC from 6 medical centers between 1 January 2022 and 1 June 2024. Pts were followed up until the last patient record as of November 1, 2024. Descriptive analyses were performed to evaluate patient and treatment characteristics. Results: A total of 322 pts were included in the study, of which 71.4% were male. The median age was 68.4 years. 79.8% of the pts came from the local county or city, 13.6% were from within the province, and 6.6% were from other provinces. A total of 97.8% of pts sought medical attention due to EC-specific symptoms, and 93.6% were diagnosed with EC through endoscopy. Squamous cell carcinoma of the esophagus accounted for 90.4%. 67.1% advanced-stage pts was progressed from earlier stages of the disease. A total of 126 (39.1%) pts had undergone surgical treatment, of which 97.5% were R0 resection, and 56.3% patients received perioperative treatment. 116 (36%) pts received definitive chemoradiotherapy. At the advanced stage, 126 (39.1%) pts had only lymph node metastasis, and 176 (54.7%) pts had organ metastasis. Among the patients with lymph node metastasis, the most common sites were the mediastinal lymph nodes (64.0%) and supraclavicular lymph nodes (32.0%). Among the patients with organ metastasis, lung metastasis (46.0%) was the most common, followed by liver metastasis (36.9%) and bone metastasis (26.7%). Information on 309 patients who received first-line (1L) treatment was recorded. 88.7% received chemotherapy, including TP (51.1%), FP (14.6%) and single-agent therapy (24.1%). Additionally, 78.3% received PD-1 inhibitor treatment, 7.1% received TKI therapy and 28.2% received radiotherapy. Information on 111 patients who received 2L+ treatment was recorded, and the regimens for subsequent treatments were more diverse. Conclusions: Most advanced EC pts received treatment at local hospitals in high-incidence areas of China. The majority of advanced-stage pts have progressed from earlier stages of the disease. Immunotherapy and chemotherapy are commonly used treatment for advanced EC. Clinical trial information: ChiCTR2400089404 .

TGFB1, which encodes TGF-β1, a potent cytokine regulating varies cellular processes including immune responses. TGF-β1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.

目的 探讨不同化疗方案治疗多发性骨髓瘤(MM)患者对其血清血管细胞黏附因子-1(sVCAM-1)、可溶性内皮细胞间黏附因子-1(sICAM-1)、血管内皮生长因子(VEGF)、β2-微球蛋白(β2-MG)水平,以及T淋巴细胞亚群的影响.方法 根据随机数字表法将南通大学附属海安医院2016年3月至2021年8月收治的100例MM患者分为对照组和观察组,各50例.两组患者入院后均给予MM规范化常规治疗,在此基础上,给予对照组患者长春新碱+多柔比星+地塞米松(VAD化疗方案)化疗,给予观察组患者硼替佐米+环磷酰胺+地塞米松(PCD化疗方案)化疗,均以21 d为1个疗程,两组患者均治疗3个疗程.比较两组患者的临床疗效,治疗前后血清sVCAM-1、sICAM-1、VEGF、β2-MG水平,全血T淋巴细胞亚群水平,以及治疗期间不良反应发生情况.结果 观察组患者总有效率显著高于对照组;与治疗前比,治疗后,两组患者血清sVCAM-1、sICAM-1、VEGF、β2-MG水平,以及CD4+CD25+T细胞百分比、CD4+CD25+/CD4+比值均显著降低,且观察组显著低于对照组(均P<0.05);两组患者不良反应总发生率比较,差异无统计学意义(P>0.05).结论 与VAD化疗方案相比,PCD化疗方案的临床疗效显著,更有利于改善MM患者的免疫功能,减轻对其肾功能的损害,抑制癌组织新生血管生成,阻止疾病的持续进展,但两种化疗方案均有一定程度的不良反应,治疗时需注意严格控制药物剂量.

Background Enhancer RNAs (eRNAs), the transcriptional products of active enhancers, are of great significance in the initial progression of cancers. However, the biological function and bioinformatics profiles of eRNA in gastric cancer remains largely enigmatic. Methods Firstly, STAD were clustered into three subtypes with the data of eRNA expression from TCeA. Then we explored the difference of the tumor immune microenvironment, transcription levels, and transcription regulation among the three clusters. Finally, samples collected from 12 patients diagnosed with STAD were used to conduct qRT-PCR, verifying the conclusion based on network database. Results The three clusters were detected to have different tumor microenvironments: Cluster A has an immune "cold" microenvironment. While cluster B features as more infiltration of immune cells, accompanied with higher expression of immune checkpoints such as PDCD1, LAG3, and TIGIT. Besides, Cluster C shows a higher stromal feature with B lineage, neutrophils, and fibroblasts. Further analyses indicated that CpG island methylation level of Cluster B is different from the other two clusters. Meanwhile, Cluster A and B showed significant enrichment of TP53 and KRAS mutation respectively while Cluster C has higher tumor mutation burden (TMB) and microsatellite instability (MSI). With the elaboration of transcriptional regulation of epigenetic clustering, we detected that Cluster A enriched in epithelial phenotype pathways. Cluster B enriched in cell-cell adhesion. Cluster C enriched in fibroblast proliferation. The clinical cohort show that Cluster B patients have lower interstitial cell characteristics and CAF infiltration. Conclusion We identified three unique epigenetic clusters of STAD through the differential activation of super-enhancers, and identified Cluster B with a higher immune infiltrating and a better prognosis, which provides a novel understanding of eRNAs and potential clinical applicability of eRNA-based molecular subtypes in gastric cancer.

Background: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced lung adenocarcinoma and significantly improve treatment outcomes. The effect of tobacco smoking on the response of immune checkpoint inhibitors is somewhat diverging. Here, we assessed the impact of tobacco exposure on the tumor microenvironment and developed a feasible tool for predicting prognosis. Methods: Whole exon sequence data and the corresponding clinical information were downloaded from the Cancer Genome Atlas. The signature was developed by the Random Forest algorithm. CIBERSORTx online tool was used to estimate immune infiltration. Functional assays were performed to assess the roles of tobacco exposure in cancer cells. Immunohistochemistry (IHC) was performed to identify and validate the immune activation status. Results: The TMB of lifelong non-smoker, current reformed smoker for over 15 years, current reformed smoker<15 years and current smoker had a significantly increasing trend in LUAD patients. In vitro tobacco exposure promoted the expression of PD-L1 and malignant phenotype of LUAD cells. In addition, patients with high Random Forest score (RFscore) had a poorer prognosis than those with low RFscore. The ROC curve analysis of RFscore revealed a promising prognostic capability. Memory activated CD4 + T cells, CD8 + t cells and memory B cells were noticeably enriched in the high RFscore group and PDCD1 appreciably upregulated in the high RFscore group as well. Furthermore, IHC results suggested that patients with high RFscore remained an immune activation status, indicating a positive correlation between RFscore and patient's immune status. Conclusion: Our analysis provides further insight into the profound impacts of tobacco exposure on tumor immune microenvironment and envisions integrative predictive models of RFscore, predicting the prognosis of smoking lung adenocarcinoma, which might help to understand the potential mechanism of smoking exposure on tumor immune microenvironment.

目的:探讨血清CEA、CK-MB水平与晚期肿瘤患者预后的关系.方法:回顾性分析168例血清CK-MB>75 U/L晚期肿瘤患者的临床资料,分析CK-MB水平与患者性别、年龄、原发肿瘤种类的关系,比较肝转移患者与无肝转移患者总生存期,分析抗肿瘤治疗前后CK-MB变化与患者总生存期的关系,比较肝转移前后CEA、CK-MB水平.结果:血清CK-MB水平与患者性别(P=0.035)及原发肿瘤种类(P=0.001)显著相关.肝转移组总生存时间较无肝转移组缩短,但差异无统计学意义(P=0.126).治疗后CK-MB下降组的总生存时间明显长于不降组,差异有统计学意义(P=0.047).肝转移后患者血清CEA、CK-MB水平分别为166.25±31.36 ng/mL和68.37±2.72 U/L,高于肝转移前的87.39±32.48 ng/mL和15.24±2.15 U/L,差异均有统计学意义(P<0.01).结论:血清CK-MB水平及其变化可作为晚期肿瘤患者的预后指标,血清CEA、CK-MB异常增高需考虑肝转移可能.

Esophageal cancer (ESCA) is the eighth most common cause of cancer-associated mortality in humans. An increasing number of studies have demonstrated that microRNAs (miRs) serve important roles in mediating tumor initiation and progression. miR-454-3p has been found to be involved in the development of various human malignancies; however, little is known about the role of miR-454-3p in esophageal cancer. In the present study, the protein and gene expression levels of miR-454-3p in ESCA tissues and cells were downregulated compared with adjacent normal tissues and normal human esophageal epithelial cells. Additionally, miR-454-3p downregulation resulted in improved survival rates in patients with ESCA, and miR-454-3p overexpression significantly suppressed cell proliferation, migration and invasion and promoted apoptosis in four ESCA cell lines (EC9706, ECA109, TE-1 and TE-8). It was found that miR-454-3p overexpression inhibited the expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) at the protein and mRNA expression levels. Furthermore, it was demonstrated that miR-454-3p inhibited ESCA cell proliferation, migration and apoptosis by targeting IGF2BP1 via the ERK and AKT signaling pathways in a subcutaneous xenograft tumor mouse model. These results showed that miR-454-3p functioned as an important tumor suppressor in ESCA by targeting IGFBP1. Therefore, miR-454-3p may be a novel prognostic biomarker and therapeutic target for patients with ESCA.

Background VHL mutation is the most common mutation in clear cell renal cell carcinoma (ccRCC). Here, we developed and validated an immune-related signature to predict the prognosis of ccRCC with VHL mutations. Methods VHL mutation status and RNA expression were analysed in the TCGA datasets and our cohort. LASSO Cox analysis was performed to develop an immune-related signature. Candidate genes for the immune-related signature were differentially expressed between VHLwt and VHLmut ccRCC patients. Results VHL mutations resulted in the downregulation of the immune response in ccRCC. To develop an immune-related signature, LASSO Cox analysis was constructed by immune-related genes that were differentially expressed between VHLwt (WHL wild type) and VHLmut (VHL mutation) ccRCC patients. The signature was developed and validated in the TCGA and our own cohort to classify patients into groups based on having a low or high risk of poor survival. Functional enrichment analysis showed that the immune-related pathway represented the major function and pathway. In addition, patients in the high-risk group had a positive correlation with low fractions of CD4 + T cells and dendritic cells and presented a lower expression of CTLA-4 and PD-1 than the low-risk group. Conclusion In this study, we proposed a novel immune-related signature, which is a feasible biomarker for predicting the overall survival in VHLmut patients with ccRCC.

目的 探讨血府逐瘀汤联合硼替佐米+地塞米松(VD)方案治疗多发性骨髓瘤的临床疗效,以及对患者血清及造血系统相关指标的影响.方法 依据治疗方法的不同将82例多发性骨髓瘤患者分为对照组(n=39)和观察组(n=43),对照组患者接受VD方案治疗,观察组患者在此基础上联合血府逐瘀汤辨证治疗.比较两组患者的造血系统相关指标、临床疗效及不良反应发生情况.结果 治疗后,两组患者红细胞沉降率(ESR)、M蛋白水平和破骨细胞数均明显低于本组治疗前,血红蛋白水平、CD4+/CD8+和成骨细胞数均明显高于本组治疗前,差异均有统计学意义(P﹤0.01);治疗后,观察组患者ESR、M蛋白水平和破骨细胞数均明显低于对照组患者,血红蛋白水平、CD4+/CD8+和成骨细胞数均明显高于对照组患者,差异均有统计学意义(P﹤0.01).观察组患者的疾病控制率为90.70％,高于对照组患者的71.79％,差异有统计学意义(P﹤0.05).对照组患者的不良反应总发生率为20.51％,高于观察组患者的16.28％,但差异无统计学意义(P﹥0.05).结论 血府逐瘀汤联合VD方案化疗治疗多发性骨髓瘤,可有效改善患者的临床疗效,减轻其对骨髓造血功能的抑制作用,提高免疫力,改善骨痛症状,安全性较高.

The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76.67%, respectively, all of which were significantly higher than those in the tissues adjacent to the tumor. The expression of these proteins represents the local invasion and stage. AR, MMP-2 and MMP-9 expression levels in HCC tissues have the potential to be employed as predictors of the progression of local cancer invasion and the tumor stage.