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.

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.

The objective of our study was to measure DLEU7-AS1 expression in de novo acute myeloid leukemia (AML) whilst also analyzing its clinical relevance. We used gene expression data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression project (GTEx) to assess the expression profile of DLEU7-AS1 in pan-cancers, cancer cell lines and normal tissues. Reverse transcription-quantitative PCR was used to measure DLEU7-AS1 expression in bone marrow from 30 normal individuals and 110 patients with de novo AML. DLEU7-AS1 expression was found to be markedly reduced in the AML samples of the TCGA pan-cancer datasets. In our PCR validation, DLEU7-AS1 expression was significantly decreased in the AML samples compared with that in controls (P<0.001). Low DLEU7-AS1 expression (DLEU7-AS1low) correlated positively with lower blood platelet counts (P=0.029). In addition, low DLEU7-AS1 expression was more frequently observed in the intermediate (58%; 44/76) and favorable karyotypes (65%; 15/23) compared with that in the poor karyotype (10%; 1/10; P=0.005). In particular, patients with high expression levels of DLEU7-AS1 (DLEU7-AS1high) showed lower complete remission rates (P=0.002) than patients with DLEU7-AS1low. Survival analysis revealed that patients with DLEU7-AS1low had longer overall survival (OS) than patients with DLEU7-AS1high (P<0.05). Multivariate Cox analysis demonstrated that in patients with non-acute promyelocytic leukemia (non-M3) who were ≤60 years old, DLEU7-AS1 expression was an independent prognostic factor for OS. Furthermore, we found distinct correlations among the expression of DLEU7-AS1, infiltration by immune cells and immune checkpoint genes in AML.

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.

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.

Hematological malignancies possess a distinctive immunologic microenvironment compared with solid tumors. Here, using an established computational algorithm (CIBERSORT), we systematically analyzed the overall distribution of 22 tumor-infiltrating leukocyte (TIL) populations in more than 2000 bone marrow (BM) samples from 5 major hematological malignancies and healthy controls. Focusing on significantly altered TILs in acute myeloid leukemia (AML), we found that patients with AML exhibited increased frequencies of M2 macrophages, compared to either healthy controls or the other four malignancies. High infiltration of M2 macrophages was associated with poor outcome in AML. Further analysis revealed that CD206, a M2 marker gene, could faithfully reflect variation in M2 fractions and was more highly expressed in AML than normal controls. High CD206 expression predicted inferior overall survival (OS) and event-free survival (EFS) in two independent AML cohorts. Among 175 patients with intermediate-risk cytogenetics, the survival still differed greatly between low and high CD206 expressers (OS; P < .0001; 3-year rates, 56% v 32%; EFS; P < .001; 3-year rates, 47% v 25%). When analyzed in a meta-analysis, CD206 as a continuous variable showed superior predictive performance than classical prognosticators in AML (BAALC, ERG, EVI1, MN1, and WT1). In summary, M2 macrophages are preferentially enriched in AML. The M2 marker CD206 may serve as a new prognostic marker in AML.

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.

MicroRNA miR-378 plays important roles in tumorigenesis by enhancing cell survival, reducing apoptosis, promoting tumor growth, angiogenesis and promoting cell migration and invasion. Abnormal expression of miR-378 has been observed in various types of cancers. The aim of this study was to investigate the expression status of miR-378 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. miR-378 overexpression was identified in 26 of 84 (31%) AML patients. The patients with miR-378 overexpression had lower hemoglobin level than those without miR-378 overexpression (66 versus 78 g/L, respectively, P=0.010). The frequency of miR-378 overexpression in FAB-M2 subtype was higher than other subtypes (44% versus 20%, P=0.032). Moreover, the frequency of miR-378 overexpression was higher in patients with t(8;21) than in others (64% versus 24%, P=0.012). The status of miR-378 expression was not correlated with the mutations of eight genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and U2AF1). The difference in relapse-free survival was observed between patients with and without miR-378 overexpression (P=0.049). These findings suggest that miR-378 up-regulation is a common event and might have an adverse impact on prognosis in AML.

Objective: SALL4 gene has been identified to stimulate the expansion of hematopoietic stem cell (HSCs) and enhance the self-renewal of HSCs. Overexpression of SALL4 has been found in several cancers. The present study was aimed to investigate the methylation status of SALL4 promoter region in acute myeloid leukemia (AML).Designs and methods: The methylation status of SALL4 promoter was analyzed in 84 patients with AML using methylation-specific PCR (MSP) and its clinical significance was evaluated.Results: Aberrant hypomethylation of SALL4 gene, which was correlated with SALL4 expression, was found in 17.8% (15/84) cases. The patients with SALL4 hypomethylation had significantly older age and higher WBCs than those without SALL4 hypomethylation. The incidence of SALL4 hypomethylation was higher in M1 subtype than in M2 and other subtypes (50%, 26% and 6%, respectively, P=0.001). SALL4 hypomethylation was associated with cytogenetically intermediate and poor groups. Although survival time of the SALL4-hypomethylated AML was shorter than that of SALL4-methylated group (4 months vs 9 months), the difference was not statistically significant (P=0.356).Conclusions: Hypomethylation of SALL4 promoter is a common event and is associated with the intermediate and poor karyotypes in AML. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

髓系分化起始反应基因88(MYD88)位于染色体3p22,编码蛋白为Toll样受体(TLR)信号传导途径中的一个重要接头分子,结构上主要包括2个功能域:N端的死亡域(DD)和C端的Toll域(TIR),在天然免疫应答和炎症反应中发挥着重要的调控作用[1-2].最近的研究发现39%活化B细胞(ABC)型弥漫大B细胞淋巴瘤(DLBCL)患者中存在MYD88基因的获得性突变[3],其中位于TIR域的L265P突变发生率最高(29%).高分辨率熔解曲线分析(High resolution melting curve analysis,HRMA)是一种新型的突变分析技术,具有灵敏度高、特异性好、成本低廉、高通量检测的优点,已在临床上得到越来越多的应用[4].我们拟建立HRMA法对MYD88 L265P突变进行检测.

This study was aimed to investigate the expression pattern of gene PDLIM4 (PDZ and LIM domain 4) and analyze its clinical correlation with the patients suffered from acute myeloid leukemia (AML). The expression pattern of PDLIM4 in AML was detected by using EvaGreen real-time quantitative PCR (RQ-PCR). The results showed that the PDLIM4 transcript significantly decreased in 94 AML patients, compared with 21 controls (P < 0.01). The decrease of PDLIM4 transcript was found in 42 (45%) AML patients. PDLIM4 low-expression occurred among the subtypes of M1/M2/M3 more frequently than that in M4/M5/M6 (56% vs 20%, P < 0.01). AML patients with PDLIM4 low-expression had an overall survival (OS) higher than that in AML patients without PDLIM4 low-expression (P < 0.05). Analysis with receiver operating characteristic curve (ROC) displayed that PDLIM4 expression possesses the diagnostic value to differentiate AML from controls, with ROC curve area of 0.865 (95% CI: 0.801-0.930). It is concluded that reduced PDLIM4 expression is a common and favorable event for the good prognosis in AML, and can be used as a potential diagnostic biomarker of cancer.

Objective: To establish high-resolution melting analysis(HRMA)assay and detect the SF3B1 mutations in patients with myelodysplastic syndrome(MDS).Methods: The PCR amplification systems with internal temperature calibrators were established with specific PCR primers against four hotspot mutation sites of SF3B1 gene(E622,H662,K666,and K700).Thirty MDS samples were amplified and analyzed by using HRMA technique.The results of HRMA were verified by DNA sequencing.Results: Abnormal melting curves were observed by HRMA assay in two MDS samples.DNA sequencing confirmed that these two samples harbored heterozygous K666M mutation and K700E mutation,respectively.The sensitivity of HRMA assay could reach 0.05.Conclusion: The HRMA assay for detecting SF3B1 mutations was established successfully and could be used to screen SF3B1 mutations rapidly in patients with MDS.

SF3B1, located on chromosome 2q33.1, encodes a core component of RNA-splicing machinery, and its mutation has been described in myelodysplastic syndromes (MDS) characterized with ring sideroblasts (RS). To explore the reliability and sensitivity of the high-resolution melting analysis (HRMA) technique for the identification of the SF3B1 mutations, mutations in 92 patients with MDS were detected in this study. The sensitivity could reach 5%, obviously higher than the 25% of direct DNA sequencing. A low frequency (5.4%) of SF3B1 mutations were identified in patients with MDS, including three cases of K700E, one case of H662Q, and one case of K666M. Further, SF3B1 mutations were more frequently recurrent in the 33% of patients with MDS characterized with RS, whereas in other subtypes of MDS, only 2.3% of patients were detected with SF3B1 mutations (p = 0.006). In conclusion, a rapid, reproducible, sensitive, and high-throughput HRMA assay has been established for the scanning of SF3B1 mutations.

Objective: To analyze the expression transcript level and promoter hypermethylation of PDZ and LIM domain 4(PDLIM4) gene and the clinical correlations in Chinese patients with chronic myeloid leukemia(CML).Methods: Real-time quantitative PCR(RQ-PCR) and real-time quantitative methylation-specific PCR(RQ-MSP) assays were used to detect the expression and methylation status of PDLIM4 gene in the bone marrow samples from CML patients.Results: Down-regulated PDLIM4 expression was found in 8/36(22%) CML cases,with significant statistical difference compared with all 21 controls(Fisher′s Exact Test,P=0.021).There was a significant correlation between PDLIM4 expression and bcr/abl fusion transcript(r=0.434,P=0.043) in CML patients.Hypermethylation of PDLIM4 promoter was detected in 13/59(22%) CML patients,but not in all 24 controls(Fisher′s Exact Test,P=0.016).PDLIM4 hypermethylation was not correlated with blood parameters(P>0.05).The frequencies of PDLIM4 promoter hypermethylation increased during the disease progression,as it was 16%(7/44),33%(2/6) and 44%(4/9) in chronic phase,accelerated phase and blast crisis,respectively.Conclusion: Hypermethylation of PDLIM4 promoter may be associated with the disease progression in CML.

The aim of this study was to investigate the expression level of the SALL4 gene and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Real-time quantitative PCR (RQ-PCR) was performed to detect the expression level of SALL4 mRNA in bone marrow mononuclear cells (BMMNC) from 35 AML, 12 CML patients and 24 iron deficiency anemia patients as controls. The results indicated that the expression level of SALL4 in AML (0%-14%, median 1.43%) was obviously higher than that in controls (0% - 1%, median 0%) (P < 0.001). SALL4 expression was positive in 65.7% (23/35) AML patients. The frequency of SALL4 expression was in M2 (86.7%, 13/15) > M3 (75.0%, 6/8) > M1 (60.0%, 3/5) > M4 (14.3%, 1/7), and the difference among 4 groups was statistically significant (P = 0.008); there was no correlation of the frequency of SALL4 expression with the age, sex, white blood cell WBC count, hemoglobin concentration, platelet count and chromosomal abnormalities of AML patients (P > 0.05). All the 13 CML cases showed positive expression of SALL4 gene (1% - 128%, median 19.39%), which was higher than that in controls (P < 0.001). The analysis of receiver operating characteristic (ROC) curve showed the area under ROC curve (AUC) of AML and CML were 0.983 (95% confidence interval: 0.95 - 1.017) and 0.997 (95% confidence interval: 0.986 - 1.007) respectively. It is concluded that SALL4 expression is a common molecular event and can be considered as a molecular marker for assisting diagnosis of AML and CML.

The aim of this study was to investigate the expression status of the helicase antigen (HAGE) transcript and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The expression of HAGE cDNA in bone marrow mononuclear cells from AML and CML patients was detected by using real-time quantitative PCR. The results indicated that overexpression of HAGE transcript (117.12% - 9842.70%, median 434.96%) was detected in 14.8% (11/74) AML patients. AML patients with HAGE cDNA expression were significantly older than those HAGE-negative patients (median 67 and 45 years, respectively, p = 0.001). HAGE cDNA expression was more frequently present among the patients with acute monoblastic leukemia (M(4) and M(5), 7 of 20, 35.0%), compared to the patients with acute non-monoblastic leukemia (M(1), M(2), M(3) and M(6), 4 of 54, 7.4%) (p = 0.007). 28.6% (8/28) cases with normal karyotypes showed HAGE cDNA overexpression, significantly higher than 7.5% (3 of 40) in those with chromosomal abnormalities (p = 0.041). Overexpression of HAGE transcript was found in 9 (34.6%) CML cases and more frequently observed at accelerated phase and blast crisis (4/4, 100%) than that at chronic phase (5/22, 22.7%) (p = 0.008). It is concluded that HAGE cDNA expression is relevant to specific subtypes of AML and to the progression of CML.

The purpose of this study was to detect the expression of RAGE-1 transcript in the bone marrow mononuclear cells (BMMNC) from patients with acute myeloid leukemia (AML) and to investigate the relationship of RAGE-1 expression level with clinical variables. The expression level of RAGE-1 gene in BMMNC from 94 newly diagnosed AML patients was measured using RQ-PCR. The relationship between RAGE-1 expression level and clinical parameters (age, sex, blood cell counts, diagnosis and prognosis) was investigated, and the levels of RAGE-1 expression were compared in patients before and after treatment. The results showed that overexpression of RAGE-1 transcript was found in 28% (26/94) AML patients (1.34 - 16.34, median 3.07). No significant difference was observed in sex, age, blood parameters and FAB subtypes between the groups with and without RAGE-1 overexpression. There was also no significant difference in the frequency of RAGE-1 overexpression among different cytogenetic risk groups and among the patients with different types of karyotypes. The level of RAGE-1 transcript significantly decreased in those patients obtained complete remission after treatment. The overall survival of AML patients with RAGE-1 overexpression was similar as that in those without RAGE-1 overexpression. It is concluded that RAGE-1 overexpression is a common event in AML, but has no impact on the prognosis of patients.

The abnormalities of SALL4 gene, which encodes a zinc-finger transcription factor and is essential for developmental events, have been found to be involved in tumorigenesis. In this study, we investigated the methylation status of the CpG island of SALL4 promoter region in myelodysplastic syndrome (MDS) using methylation-specific PCR (MSP). Aberrant hypomethylation of SALL4 gene was found in 21.7% (18/83) of the cases analyzed. A significantly positive correlation was identified between the level of SALL4 transcript and the status of SALL4 hypomethylation (R=0.641, P<0.001). No correlation was found between SALL4 hypomethylation and clinical parameters. However, the frequency of SALL4 hypomethylation significantly increased in higher risk MDS (14% in Low/Int-1 versus 39% in Int-2/High, P=0.031). The association between SALL4 hypomethylation and the mutations in three methylation modifiers (IDH1, IDH2 and DNMT3A) was not observed. Although the estimated 50% survival time of the SALL4-hypomethylated group was shorter than that of SALL4-methylated group (11.0 months vs. 20.0 months), the difference was not statistically significant (P=0.430). These findings suggest that hypomethylation of SALL4 promoter is a common event in MDS.