Esophageal squamous cell carcinoma (ESCC) is characterized by immune evasion and poor clinical outcomes. Autophagy has been implicated in tumor-immune interactions, but the molecular factors linking autophagy-associated processes to immune modulation in ESCC remain incompletely defined. We analyzed PSD3 expression in ESCC tissues and its association with prognosis and MHC-I-related molecules. Protein interactions were assessed by co-immunoprecipitation. Autophagy-associated marker changes, autophagic flux, total MHC-I protein levels, and immune cell infiltration were evaluated following PSD3 knockdown in murine and human ESCC models using Western blotting, tandem fluorescent LC3 reporter assays, immunohistochemistry, and single-cell RNA sequencing. Epistasis analysis was performed by silencing ATG7 following PSD3 knockdown. PSD3 was upregulated in ESCC and associated with unfavorable prognosis. PSD3 knockdown was accompanied by changes in autophagy-associated markers and reduced autophagosome abundance. In KYSE150 cells, tandem fluorescent mCherry-eGFP-LC3B analysis showed that PSD3 silencing impaired autophagic flux. PSD3 co-immunoprecipitated with ATG7, BAG3 and TBK1, supporting its association with autophagy-related protein complexes. PSD3 knockdown increased total MHC-I protein levels and was associated with enhanced immune cell infiltration in syngeneic tumor models. Furthermore, ATG7 silencing following PSD3 knockdown selectively restored HLA-E expression, while HLA-ABC and HLA-F showed no clearly distinguishable change. These findings support a working model in which PSD3 is linked to autophagy-associated immune modulation in ESCC. While additional studies are required to define pathway hierarchy and antigen-presentation function more directly, PSD3 emerges as a candidate molecular node for further mechanistic and translational investigation.

Mitochondrial ribosomal protein L13 (MRPL13) has been implicated in tumor progression, but its relevance to esophageal squamous cell carcinoma (ESCC) remains insufficiently defined. Because mitochondrial adaptation can influence tumor cell fitness under oncogenic and oxidative stress, we investigated whether MRPL13 is associated with aggressive ESCC biology and mitochondrial functional states. We analyzed MRPL13 expression, clinical associations, survival relevance, mutation patterns, immune-related correlates, and pathway enrichment using TCGA and related public datasets, with an emphasis on ESCC-specific analyses. Experimental validation was performed using paired ESCC tissues and KYSE150 cells with shRNA-mediated MRPL13 knockdown. Western blotting, colony formation, transwell migration/invasion assays, mitochondrial membrane potential assessment, and ROS staining were used to evaluate protein expression, cellular behavior, and mitochondrial status. MRPL13 was up-regulated in ESCC and its expression was associated with tumor stage and unfavorable prognosis. MRPL13 expression correlated with a set of cancer-associated genes, including SIX2, SPP1, COL11A1, DSC3, and CCNA1, several of which were also increased at the protein level in paired ESCC tissues. ESCC tumors with higher MRPL13 expression showed distinct mutation and immune-related expression patterns; however, these immune associations were interpreted as correlates of tumor state rather than direct evidence of immune regulation. Pathway analyses indicated enrichment of MAPK-related signaling in MRPL13-high tumors. Consistently, MRPL13 knockdown in KYSE150 cells reduced phosphorylation of MEK1/2, ERK1/2, JNK1/2, and p38, impaired colony formation and in vitro migration/invasion, decreased mitochondrial membrane potential, and increased intracellular ROS levels. These findings suggest that MRPL13 identifies an aggressive ESCC state in which mitochondrial integrity, MAPK-associated signaling, and tumor cell fitness are functionally coupled. Rather than establishing MRPL13 as a fully defined upstream driver, our data support a more restrained interpretation: MRPL13 may help ESCC cells maintain mitochondrial stress tolerance, and its loss exposes a vulnerability characterized by reduced MAPK phosphorylation, impaired clonogenic and invasive capacity, mitochondrial depolarization, and ROS accumulation.

Cancer cells evade immune detection through checkpoint molecules like PD-L1 and PD-L2 which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of pyruvate kinase M2 (PKM2) in modulating the immune checkpoint molecules PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. PKM2 knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of PD-L1 and PD-L2. In silico analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8 + T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of PKM2 results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.

Chemoresistance remains a major challenge in esophageal squamous cell carcinoma (ESCC) therapy, particularly resistance to 5-Fluorouracil (5-FU). This study uncovers how 5-FU resistance reprograms the tumour microenvironment, primarily through the up-regulation of ADAM10 and the release of soluble PD-L1, which collectively facilitate immune evasion. Using a 5-FU-resistant AKR mouse ESCC cell line (5-FU-AKR) and its parental counterpart, we applied third-generation DNA sequencing, proteomic analysis, and single-cell RNA sequencing to unravel the resistance-associated molecular and cellular shifts. We found that ADAM10 is significantly up-regulated in 5-FU-AKR cells, promoting soluble PD-L1 release, thereby limiting CD8+ T cell infiltration. Xenograft models further demonstrated enhanced tumourigenicity and immune exclusion in 5-FU-resistant tumours. These findings highlight a novel mechanism of immune suppression driven by ADAM10, suggesting that targeting the ADAM10-PD-L1 axis may restore anti-tumour immunity and improve treatment outcomes for 5-FU-resistant ESCC.

Introduction:Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor outcomes and limited targeted therapeutic options. While protein phosphatase 1γ (PP1γ) is overexpressed in various cancers, its role and mechanism in ESCC remains unclear. This study investigated the involvement of PP1γ in ESCC progression, particularly concerning YAP1 dephosphorylation and its regulation on stem cell markers. Methods:The expression levels of PP1γ, YAP1, SOX2, and NANOG in ESCC tissues and adjacent non-cancerous tissue samples were analyzed using bioinformatics and immunohistochemistry. Their association with clinical features and prognosis were also analyzed. Functional assays were performed in KYSE150 cells to assess the effects of PPP1CC silencing on cell proliferation, migration, and invasion. Western blotting and qRT-PCR were used to measure the expression of YAP1, phosphorylated YAP1 (p-YAP1), SOX2, and NANOG. Results and discussion:We found that PP1γ was highly expressed in ESCC and was significantly associated with poor prognosis, lymph node metastasis, and advanced pathological stages. Patients with high PP1γ levels had significantly shorter overall survival and progression-free survival (P < 0.05). In functional assays, silencing of PPP1CC in KYSE150 cells resulted in a marked decrease in cell proliferation, as measured by CCK-8 assays (P < 0.01). Colony formation assays confirmed the reduced colony-forming ability in PPP1CC-silenced cells (P < 0.01). Furthermore, Transwell invasion and migration assays demonstrated a significant reduction in both cell migration and invasion (P < 0.01). Western blot analysis revealed that silencing PPP1CC led to an increase in p-YAP1 and the ratio of p-YAP1 to YAP1, indicating inhibited YAP1 activity, alongside significant reductions in YAP1 and SOX2 protein levels (P < 0.05), while NANOG expression remained unchanged. This change was further confirmed by the qRT-PCR. Conclusively, PP1γ may promote ESCC progression by regulating YAP1 dephosphorylation and enhancing the expression of SOX2. The PP1γ/YAP1/SOX2 axis may provide potential therapeutic targets for ESCC treatment.

CD82, traditionally recognized as a metastasis suppressor within the tetraspanin family, has emerged as a key player in diverse cancer-related processes beyond its canonical functions. This review highlights recent research on the non-canonical roles of CD82 in cancer progression, with a particular focus on its regulation of immune cell interactions, its impact on tumor microenvironment modulation, and its potential as both a therapeutic target and a biomarker. By examining the novel functions of CD82 in immune modulation and its influence on key signaling pathways, we propose that CD82 offers promising avenues for therapeutic interventions in cancer. This paper provides a comprehensive synthesis of the current understanding of CD82's expanded roles, underscoring its potential in improving cancer diagnosis and therapy.

PH and Sect. 7 domain-containing protein 3 (PSD3) has been reported to be associated with some cancers, but its role in esophageal squamous cell carcinoma (ESCC) has not been thoroughly examined. The purpose of this study was to investigate the expression of PSD3 in ESCC and determine whether PSD3 is regulated by pyruvate kinase type M2 (PKM2) to affect the malignant phenotype of ESCC cells. First, we found that PSD3 was highly expressed in ESCC tissues and correlated with ESCC lymph node metastasis. In vitro, PSD3 promoted the proliferation, migration and invasion of ESCC cells. In vivo, PSD3 accelerated ESCC growth and metastasis. Next, the interaction between PSD3 and PKM2 was examined, and the results showed that PSD3 was directly regulated by PKM2. Functionally, PSD3 was regulated by PKM2 to promote the proliferation, migration and invasion of ESCC cells. Mechanistically, PSD3 was regulated by PKM2 to upregulate the expression of Vimentin and Snail and downregulate the expression of E-cadherin. Collectively, all the data we show here demonstrate that PSD3, regulated by PKM2, endows growth and metastasis advantages in ESCC by modulating epithelial-mesenchymal transition (EMT) progression.

Recent studies have increasingly focused on PIK3CA mutations in esophageal squamous cell carcinoma (ESCC); however, the clinicopathological significance of these mutations within the tumor microenvironment remains underexplored. This study aimed to evaluate and compare the clinicopathological significance of mutated PIK3CA in ESCC using in silico analyses of the ESCC dataset from the TCGA database. We assessed prognosis, differential expression, correlation with immune cell infiltration and immune checkpoint expression, heterogeneity, and drug sensitivity in comparison with wild-type PIK3CA. Our findings revealed that PIK3CA mutation is associated with increased tumor mutation burden and significantly correlated with the infiltration of CD4 naive and effector memory CD4 T cells. Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC.

Short for pyruvate kinase M2 subtype, PKM2 can be said of all‐round player that is notoriously known for its metabolic involvement in glycolysis. Holding a dural role as a metabolic or non‐metabolic (kinase) enzyme, PKM2 has drawn extensive attention over its biological roles implicated in tumor cells, including proliferation, migration, invasion, metabolism, and so on. wandering PKM2 can be transboundary both intracellularly and extracellularly. Specifically, PKM2 can be nuclear, cytoplasmic, mitochondrial, exosomal, or even circulate within the body. Importantly, PKM2 can function as an RNA‐binding protein (RBP) to self‐support its metabolic function. Despite extensive investigations or reviews available surrounding the biological roles of PKM2 from different angles in tumor cells, little has been described regarding some novel role of PKM2 that has been recently found, including, for example, acting as RNA‐binding protein, protection of Golgi apparatus, and remodeling of microenvironment, and so forth. Given these findings, in this review, we summarize the recent advancements made in PKM2 research, mainly from non‐metabolic respects. By the way, PKM1, another paralog of PKM2, seems to have been overlooked or under‐investigated since its discovery. Some recent discoveries made about PKM1 are also preliminarily mentioned and discussed.

Chronic apical periodontitis (CAP) is characterized by inflammation and destruction of the apical periodontium that is of pulpal origin, appearing as an apical radiolucent area, and does not produce clinical symptoms. Little is known about whether the PD-1/PD-L1 ratio is associated with the balance between RANKL and OPG in CAP. The relationship between PD-1/PD-L1 and RANKL/OPG in CAP is investigated in this study. A CAP rat model was established using Sprague-Dawley rats. The pulp chambers were exposed to the oral cavity to allow bacterial contamination. The apical tissues of the bilateral mandibular first molars were analyzed for histological morphology using hematoxylin and eosin (H E) staining. Immunohistochemistry and qRT-PCR were used to determine the expression of PD-1, PD-L1, OPG, and RANKL mRNA and proteins in periapical tissues and mandibular samples, respectively. The radiological images indicated a poorly defined low-density shadow and alveolar bone resorption after periodontitis induction. Histological analysis revealed an infiltration of inflammatory cells and alveolar bone resorption in the periapical tissues. Mandibular mRNA and periapical protein expression of PD-1, PD-L1, and RANKL was upregulated 7–28 days after periodontitis induction, while the expression of OPG was downregulated. No significant relationship was observed between PD-1/PD-L1 and RANKL/OPG at either mRNA or protein levels in CAP. There is an increased expression of PD-1, PD-L1, and RANKL and a decreased expression of OPG, indicating progression of CAP.

IntroductionMycoplasma pneumoniae (MP) is the major cause of respiratory infections that threaten the health of children and adolescents worldwide. Therefore, an early, simple, and accurate detection approach for MP is critical to prevent outbreaks of MP-induced community-acquired pneumonia.MethodsHere, we explored a simple and accurate method for MP identification that combines loop-mediated isothermal amplification (LAMP) with the CRISPR/Cas12b assay in a one-pot reaction.ResultsIn the current study, the whole reaction was completed within 1 h at a constant temperature of 57°C. The limit of detection of this assay was 33.7 copies per reaction. The specificity of the LAMP-CRISPR/Cas12b method was 100%, without any cross-reactivity with other pathogens. Overall, 272 clinical samples were used to evaluate the clinical performance of LAMP-CRISPR/Cas12b. Compared with the gold standard results from real-time PCR, the present method provided a sensitivity of 88.11% (126/143), specificity of 100% (129/129), and consistency of 93.75% (255/272).DiscussionTaken together, our preliminary results illustrate that the LAMP-CRISPR/Cas12b method is a simple and reliable tool for MP diagnosis that can be performed in resource-limited regions.

Compared with those in adenocarcinoma, PIK3CA mutations are more common in squamous cell carcinoma (SCC), which arises from stratified squamous epithelia that are usually exposed to adverse environmental factors. Although hotspot mutations in exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L and H1047R, are frequently encountered in the clinic, their clinicopathological meaning remains to be determined in the context of SCC. Considering that few reviews on PIK3CA mutations in SCC are available in the literature, we undertook this review to shed light on the clinical significance of PIK3CA mutations, mainly regarding the implications and ramifications of PIK3CA mutations in malignant cell behavior, prognosis, relapse or recurrence and chemo- or radioresistance of SCC. It should be noted that only those studies regarding SCC in which PIK3CA was mutated were cherry-picked, which fell within the scope of this review. However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.

Vimentin has been considered a canonical marker of epithelial-mesenchymal transition (EMT) and is associated with tumor escape characterized by aberrant PD-L1 expression. However, whether there is a relationship between vimentin and PD-L1 in esophageal squamous cell carcinoma (ESCC) remains poorly understood. The immunological involvement of vimentin in ESCC was first analyzed by multiplex immunofluorescence staining in ESCC tissue microarray followed by a xenografted mouse model. In vivo, C57BL/6 mice were subcutaneously transplanted with AKR cells after stable silencing of vimentin. In vivo results showed that in addition to PD-L1 and PD-L2 expression, vimentin expression was inversely correlated with CD8+ T-cell infiltration. Mechanistically, vimentin can directly interact with PD-L1 and promote nuclear translocation of PD-L1 in AKR cells. In addition, SEMA6C, STC-2 and TRAILR2 were identified as cytokines modulated by vimentin. Blockade of STC-2 and TRAILR2 in co-culture with their own primary antibodies was shown to recruit more CD8+ T cells than controls. Together, these data strongly suggest targeting Vimenin to overcome the immune cycle in ESCC.

Thought of as a metastasis-associated gene, however, NME/NM23 nucleoside diphosphate kinase 4 (NME4) has rarely been described in the context of the tumour microenvironment. To understand the immunological implications of NME4 in oesophageal squamous cell carcinoma (ESCC), we used multiplex immunohistochemistry to analyse the clinicopathological and prognostic importance of NME4 expression. Then, after establishing a syngeneic tumour model with a C57BL/6 mouse strain that can recapitulate the tumour microenvironment of humans, we examined the immunological involvement of NME4 expression. To explore the underlying molecular mechanism, via quantitative proteomics and protein microarray screening, we investigated the potential signalling pathways involved. The clinicopathological and prognostic importance of NME4 expression is limited in ESCC patients. In vivo, single-cell RNA sequencing showed that NME4 strikingly prevented CD8+ T cells from infiltrating the tumour microenvironment in murine ESCC. Mechanistically, we mapped out the NFκB2-CCL5 axis that was negatively controlled by NME4 in the murine ESCC cell line AKR. Collectively, these data demonstrated that regulation of NFκB2-CCL5 axis by NME4 prevents CD8+ T cells infiltration in ESCC.

Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20

Abstract Purpose To investigate the effect of MYCN on the proliferation, invasion and migration of NB and its molecular mechanism. Methods We first compared the expression level of MYCN mRNA in NB cells by PCR. Next, the expression level of miR-20a-5p in NB cells was detected by PCR. Then, cell counting kit-8, wound healing and transwell assays were used to determine the ability of proliferation, migration and invasion of NB cells. Both cells were infected with miR-20a-5p lentivirus particles, and then the infection efficiency was detected by PCR. Repeat the above cell function test to determine the proliferation, migration, invasion and apoptosis of NB cells after overexpression or low expression of miR-20a-5p. Bioinformatics analysis was used to predict the binding sites of miR-20a-5p and NFKBIB. A double luciferase reporting assay was used to verify the targeting relationship between miR-20a-5p and NFIBIB. WB confirmed that miR-20a-5p could activate the NF- κB pathway. Results MYCN and miR-20a-5p can promote the proliferation, invasion and migration of NB cells, and inhibit NFKBIB by upregulating miR-20a-5p, thereby activating the NF- κB pathway. Conclusion In this study, we speculate that the MYCN/miR-20a-5p/NFKBIB/NF- κ B signaling axis can promote the proliferation, invasion and migration of NB cells.

The involvement of the mitochondrial ribosomal protein 13 (MRPL13) gene in the development of adenocarcinoma has been previously reported. However, the clinicopathological significance of MRPL13 in squamous cell carcinoma (SCC) remains poorly understood. To gain insight into the clinicopathological and immunological implications of MRPL13 expression in SCC, we conducted a bioinformatic analysis utilizing various available databases, including TIMER 2.0, Xiantao academic tool and TISIDB, attempting to evaluate the abnormal expression, prognosis and immunological correlation of MRPL13 in the pan-SCC setting. Subsequently, we conducted experimental verification using an esophageal squamous cell carcinoma (ESCC) tissue array subjected to multiplexed immunofluorescent (mIF) staining. The ESCC tissue array we used consists of 93 dots of ESCC and 86 dots of matched adjacent normal tissues (ANT). Data from in silico analyses showed that MRPL13 mRNA is significantly up-regulated and correlated with infiltration of CD8+ T cells in pan-SCC. However, in silico analyses did not support the prognostic role of MRPL13 in SCC. Consistently, data from the ESCC tissue array showed that MRPL13 was remarkably elevated in ESCC tissues relative to ANT in stroma, which was controlled by pan-cytokeratin (pan-CK) staining. In the epithelia, no significant difference was identified between ESCC and ANT. Furthermore, MRPL13 expression markedly correlated with the infiltration of CD8+ T cells in the stromal region but not in the epithelial region. Prognostically, no significant association was observed between MRPL13 expression and overall survival, regardless of epithelial or stromal section. Through these pan-SCC analyses, we have expanded the understanding of MRPL13 previously reported, in particular, underscoring the immunological involvement of MRPL13 in the tumor microenvironment of SCC that has been under-recognized before, suggesting that MRPL13 may regulate the infiltration of CD8+ T cells into the SCC microenvironment.

目的 分析并探讨微小RNA-133b(miR-133b)和M2型丙酮酸激酶(M2 pyruvate kinase,PKM2)在食管鳞癌组织中的表达及临床意义.方法 选取2020年1月至2021年12月于西南医科大学附属医院收治的72例食管鳞癌患者手术切除的癌组织作为研究组;配对癌旁正常食管组织作为对照组.采用原位杂交技术检测miR-133b的表达,运用免疫组化法检测PKM2的表达.比较两组miR-133b、PKM2表达差异,分析食管鳞癌组织miR-133b与PKM2表达的相关性及与肿瘤浸润深度、分化程度、淋巴结转移等临床病理特征的关系.结果 miR-133b在对照组中的表达水平显著高于研究组,差异有显著性(P<0.05).PKM2在研究组中的表达水平显著高于对照组,差异有显著性(P<0.05).miR-133b低表达组PKM2高表达率显著高于miR-133b高表达组,差异有显著性(P<0.05).Spearman相关性分析结果显示,miR-133b和PKM2在食管鳞癌组织中的表达呈显著负相关(r=-0.532,P=0.000).食管鳞癌组织中miR-133b的表达水平与患者性别、年龄、肿瘤部位、病理类型、肿瘤直径、病理分级、浸润深度、脉管转移、神经转移及淋巴结转移均无关(P>0.05).PKM2在男性、高龄(年龄≥60岁)、发生于食管下段、溃疡型、肿瘤直径≤5cm、高/中分化、发生脉管转移和淋巴结转移的食管鳞癌患者中高表达率更高(P<0.05).49例食管鳞癌淋巴结转移组织中,PKM2高表达率显著高于miR-133b(P<0.05).结论 食管鳞癌组织中,miR-133b表达下调,PKM2表达上调.miR-133b可能通过下调PKM2的表达从而抑制食管鳞癌的浸润转移.

目的 观察通用转录因子3(BTF3)在食管鳞癌细胞中表达情况,探讨BTF3对食管鳞癌细胞增殖、凋亡的影响及可能机制.方法 取对数生长期正常食管鳞状上皮细胞株Het-1A、食管鳞癌细胞株KYSE150,采用Western blot法检测BTF3蛋白相对表达量.对数生长期KYSE150细胞分为BTF3敲低组(转染BTF3敲低慢病毒)、TWIST1过表达组(转染BTF3敲低+TWIST1过表达慢病毒)、基质金属蛋白酶-2(MMP-2)过表达组(转染BTF3敲低+MMP-2过表达慢病毒)、对照组(转染阴性对照慢病毒).BTF3敲低组、对照组细胞采用实时荧光定量PCR法检测BTF3 mRNA相对表达量,采用Western blot法检测BTF3、MMP-2、TWIST1、β-catenin、p-β-catenin蛋白相对表达量,采用流式细胞术检测细胞凋亡率.转染48、72、96、120 h时,应用Celigo细胞成像分析仪检测4组细胞增殖倍数.结果 KYSE150细胞BTF3 蛋白相对表达量(1.42±0.14)高于 Het-1A 细胞(1.09±0.10)(t=3.289,P=0.030).BTF3 敲低组细胞 BTF3 mRNA 和蛋白相对表达量(0.04±0.01、0.75±0.12)均低于对照组(1.25±0.44、1.03±0.05)(t=4.756,P=0.009;t=3.645,P=0.022),细胞凋亡率[(13.01±0.10)％]高于对照组[(3.34±0.14)％](t=97.670,P＜0.001);BTF3 敲低组细胞 MMP-2、TWIST1、p-β-catenin 蛋白相对表达量(0.65±0.02、0.92±0.04、0.56±0.08)均低于对照组(1.05±0.05、1.09±0.08、0.99±0.02)(t=13.350,P＜0.001;t=3.162,P=0.034;t=9.360,P＜0.001),β-catenin 蛋白相对表达量(0.91±0.10)与对照组(0.97±0.07)比较差异无统计学意义(t=1.152,P=0.314).转染48、72、96、120 h时,BTF3敲低组、TWIST1过表达组、MMP-2过表达组细胞增殖倍数均低于对照组(P＜0.05),TWIST过表达组均高于BTF3敲低组(P＜0.05),BTF3敲低组与MMP-2过表达组比较差异均无统计学意义(P＞0.05).结论 敲低食管鳞癌细胞中BTF3表达可抑制β-catenin磷酸化及TWIST1表达,从而抑制上皮-间质转化和细胞增殖,促进细胞凋亡.

Initially discovered in chronic viral infection and then extended to tumor, 'T-cell exhaustion' is a broad term describing the response of T cells to chronic antigen stimulation. By definition, whether T-cell exhaustion occurs in diffuse large B-cell lymphoma (DLBCL) remains largely unknown because little has been described. Here, the immune-suppressing checkpoint molecules involved in T-cell exhaustion, including PD-1, PD-L1, TIM-3 and TIGIT, whose expression levels were analyzed in DLBCL, were retrieved from the GEPIA database. Compared with the normal control, CD8A, TNFA, IFNG and GZMA were markedly elevated in DLBCL, indicating that infiltrated CD8+ T cells predominate in DLBCL. Meanwhile, inhibitory immune checkpoints, such as PD-1, PD-L1, TIGIT and TIM-3 were drastically higher in DLBCL. PTEN, WNT2 and DKK3 expression were also appraised. It was revealed that PTEN was lower in DLBCL, without being statistically significant. In contrast with PTEN, DKK3 and WNT2 were shown to be pronouncedly higher in DLBCL relative to the normal control. Prognostically, only TIGIT was found to be associated with overall survival in DLBCL. Collectively, all the data we curetted from the GEPIA and TIMER 2.0 databases explicitly indicate that CD8+ T cell exhaustion took place, which may be linked with lower PTEN in DLBCL. To the best of our knowledge, this is the first bioinformatic report explicitly proposing that CD8+ T cell exhaustion occurs in DLBCL, which may be associated with lower PTEN.