Table S3 includes primers for QPCR

INTRODUCTION:Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer worldwide. Long non-coding RNA (lncRNAs) are non-protein coding RNAs that are involved in lung cancer. This study aimed to develop a lncRNA-based risk assessment model based on RNA methylation to evaluate the prognosis of patients with LUAD. METHOD:The TCGA-LUAD dataset consisted of 524 primary tumor samples and 59 normal samples, and the validation set (GSE3121011), which included 246 patients with LUAD, was used for this analysis.Pearson's correlation analysis was used to identify lncRNAs associated with RNA methylation in LUAD. Univariate, least absolute shrinkage and selection operators, and multivariate Cox analyses were used to construct the prognostic model. Gene oncology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to identify enriched biological processes. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to visualize the dataset and gene set variation analyses. Kaplan-Meier and decision curve analyses were used to assess the accuracy. qRT-PCR was used to verify the expression of lncRNAs. Invasion and cell scratch assays were conducted to evaluate migration capacity, and colony formation experiments were performed to assess proliferation ability. RESULT:Ten RNA methylation-associated lncRNAs were identified to construct risk features. According to the risk model, the patients were categorized into low- and high-risk groups, with the latter exhibiting a less favorable prognosis. The expression levels of the lncRNAs exceeded those in lung epithelial cells. After siRNA transfection, the proliferation and migration abilities of the tumor cells were significantly reduced. The risk-scoring model may be a potential indicator for predicting the sensitivity of patients with LUAD to immunotherapy. CONCLUSION:The model constructed in this study can accurately predict the prognosis of patients with LUAD, and holds promise for future immunotherapies.

INTRODUCTION:Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive.METHODS:We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells.RESULTS:We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects.CONCLUSION AND FUTURE PERSPECTIVE:Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC.

Integrin β5 (ITGB5) is a pivotal player in the pathogenesis of gastric cancer (GC). We aimed to explore the potential value of ITGB5 as a predictor of diagnosis and immunotherapy in gastric cancer. The expression of ITGB5 in GC was assessed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and verified through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Kaplan-Meier curves were conducted to evaluate the prognostic significance. The immune cells infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS) were examined using CIBERSORT, TIMER, and TISIDB. In addition, colony formation, scratch assays, and transwell assays were employed to determine the impact on tumor progression and metastasis. CD276 expression was detected by western blotting following the knockdown of ITGB5. ELISA was utilized to measure serum ITGB5 levels. The expression of ITGB5 in GC tissue surpassed that in normal tissue, it might contribute to GC pathogenesis through pathways including PI3K-AKT, ECM-receptor interaction, and TGF-beta. The elevated ITGB5 expression is associated with poor prognosis in GC patients. In addition, a strong positive association between ITGB5 overexpression and the infiltration levels of macrophages and monocytes, and it significantly influenced immune response. Moreover, lower expression of ITGB5 was associated with better immunotherapy efficacy. Subsequent investigation demonstrated that silencing of ITGB5 suppressed the proliferation and migration of GC cell lines in vitro. ITGB5 expression was positively correlated with CD276 expression and the knockdown of ITGB5 resulted a notable decrease CD276 expression. Futhermore, a significantly high level of serum ITGB5 was observed in GC patients. The combined assessment of ITGB5, CEA, and CA19-9 improved the diagnostic accuracy. ITGB5 potentially serve as both a diagnostic biomarker and therapeutic target in managing GC.

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma.

To establish a nomogram for predicting brain metastasis (BM) in primary lung cancer at 12, 18, and 24 months after initial diagnosis. In this study, we included 428 patients who were diagnosed with primary lung cancer at Harbin Medical University Cancer Hospital between January 2020 and January 2022. The endpoint event was BM. The patients were randomly categorized into two groups in a 7:3 ratio: training (n = 299) and validation (n = 129) sets. Least absolute shrinkage and selection operator was utilized to analyze the laboratory test results in the training set. Furthermore, clinlabomics-score was determined using regression coefficients. Then, clinlabomics-score was combined with clinical data to construct a nomogram using random survival forest (RSF) and Cox multivariate regression. Then, various methods were used to evaluate the performance of the nomogram. Five independent predictive factors (pathological type, diameter, lymph node metastasis, non-lymph node metastasis and clinlabomics-score) were used to construct the nomogram. In the validation set, the bootstrap C-index was 0.7672 (95

Cardiovascular disorders are commonly prevalent in cancer patients, yet the mechanistic link between them remains poorly understood. Because neutrophil extracellular traps (NETs) have implications not just in cardiovascular diseases (CVD), but also in breast cancer (BC), it was hypothesized to contribute to CVD in the context of oncogenesis. We established a mouse model using nude mice to simulate liver metastasis of triple-negative BC (TNBC) through the injection of MDA-MB-231 cells. Multiple imaging and analysis techniques were employed to assess the cardiac function and structure, including echocardiography, HE staining, Masson staining, and transmission electron microscopy (TEM). MDA-MB-231 cells underwent treatment with a CaSR inhibitor, CaSR agonist, and NF-κB channel blocker. The phosphorylation of NF-κB channel protein p65 and the expression and secretion of IL-8 were assessed using qRT-PCR, Western Blot, and ELISA, respectively. In addition, MDA-MB-231 cells were co-cultured with polymorphonuclear neutrophils (PMN) under varying conditions. The co-localization of PMN extracellular myeloperoxidase (MPO) and DNA were observed by cellular immunofluorescence staining to identify the formation of NETs. Then, the cardiomyocytes were co-cultured with the above medium that contains NETs or not, respectively; the effects of NETs on cardiomyocytes apoptosis were perceived by flow cytometry. The ultrastructural changes of myocardial cells were perceived by TEM, and ELISA detected the levels of myocardial enzyme (LDH, MDA and SOD). Overall, according to our research, CaSR has been found to have a regulatory role in IL-8 secretion in MDA-MB-231 cells, as well as in the formation of NETs by PMN cells. These findings suggest CaSR-mediated stimulation in PMN can lead to increased NETs formation and subsequently to cytotoxicity in cardiomyocytes, which potentially via activation of the NF-κB signaling cascade of BC cell.

PDF file, 36K, Primers for qRT-PCR.

PDF file, 12461K, Immunohistochemical staining patterns.

Immunotherapy is widely used to treat various cancers, but patients with gastric cancer (GC), which has a high mortality rate, benefit relatively less from this therapy. Platelets are closely related to GC progression and metastasis. This study aimed to find novel potential biomarkers related to platelet function to predict GC and immunotherapy efficacy. First, based on platelet activation, signaling, and aggregation (abbreviation: function)-related genes (PFRGs), we used the least absolute shrinkage and selection operator (Lasso) regression method to construct a platelet-function-related genes prognostic score (PFRGPS). PRFGPS was verified in three independent external datasets (GSE26901, GSE15459, and GSE84437) for its robustness and strong prediction performance. Our results demonstrate that PRFGPS is an independent prognostic indicator for predicting overall survival in patients with GC. In addition, prognosis, potential pathogenesis mechanisms, and the response to immunotherapy were defined via gene set enrichment analysis, tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion (TIDE), microsatellite instability, and immune checkpoint inhibitors. We found that the high-PRFGPS subgroup had a cancer-friendly immune microenvironment, a high TIDE score, a low tumor mutational burden, and relatively low microsatellite instability. In the immunophenoscore model, the therapeutic effect on anti-PD-1 and anti-CTLA-4 in the high-PRFGPS subgroup was relatively low. In conclusion, PRFGPS could be used as a reference index for GC prognosis to develop more successful immunotherapy strategies.

Hippo通路最先在果蝇体内被发现,在哺乳动物中具有高度保守性,其主要功能是调节器官发育及维持内环境稳态.此外,越来越多的研究发现Hippo通路的失调与肿瘤的发生、发展密切相关.本文主要总结了 Hippo通路在调节肿瘤细胞增殖、凋亡、转移、肿瘤干细胞特性以及肿瘤免疫抑制等方面的作用,希望可以为相关研究提供借鉴和参考.

目的 探讨术前外周血系统性免疫炎症指数(Systemic immune-inflammation index,SII)、中性粒细胞与淋巴细胞比值(Neutrophil to lymphocyte ratio,NLR)、血小板与淋巴细胞比值(Platelet to lymphocyte radio,PLR)与可切除胃癌患者预后的相关性及其临床意义.方法 回顾性分析2013年10月—2015年2月哈尔滨医科大学附属肿瘤医院收治的226例经手术治疗胃癌患者的临床病理资料.评估并比较SII、NLR、PLR在可切除胃癌患者中的预后价值.结果 胃癌组SII、NLR、PLR显著高于健康对照组,差异均有统计学意义(P<0.05).多因素Cox回归分析结果显示SII高(HR=2.947,95％CI:1.345～6.454,P=0.007)、NLR高(HR=2.876,95％CI:1.445～5.724,P=0.003)、T分期越高(HR=5.885,95％CI:1.641～21.099,P=0.007)、有远处转移(HR=3.010,95％CI:1.472～6.154,P=0.003)是影响可切除胃癌患者预后的独立危险因素.SII预测可切除胃癌患者结局的ROC曲线下面积为0.840,灵敏度为86.6％,特异度为68.0％,高于NLR、PLR及CA199,且差异有统计学意义(P<0.05).结论 SII对可切除胃癌患者生存结局的评估价值优于NLR和PLR.

外泌体是细胞激活或损伤释放到细胞外液中的一种囊泡状物质,其内部装载了多种蛋白质、脂质和mRNA/microR-NA,在机体细胞间的通讯过程中起着重要作用.前期关于外泌体的研究大多集中在肿瘤的发病机制、诊断和治疗领域,而近年来外泌体在心血管系统疾病中的作用也越来越受到关注.目前,外泌体在糖尿病心肌病、心肌梗死、动脉粥样硬化、心力衰竭等疾病中取得了较多进展,可能成为临床心血管疾病治疗的一个潜在的新方向.

Ischemia-reperfusion (I/R) injury caused by acute myocardial infarction (AMI) can initiate a strong inflammatory response. Polymorphonuclear cells (PMNs) are the most important inflammatory cells. Our previous studies found that the calcium-sensing receptor (CaSR) regulates the proinflammatory effects of PMNs. However, the role and mechanism of CaSR-regulated PMNs in I/R injury remain uncertain. A rat AMI model was developed in this study and showed that the expression of CaSR on PMNs increased in AMI; however, the levels of Bcl-xl and SOD in myocardial tissue decreased, while Bax and MDA levels increased. Then, after coculture with CaSR-stimulated PMNs, the expression of Bcl-xl in cardiomyocytes significantly increased, Bax expression and the apoptotic rate decreased, and ROS production was significantly inhibited. At the same time, the cardiomyocyte damage caused by hypoxia-reoxygenation was reduced. Furthermore, we found that exosomes derived from PMNs could be taken up by cardiomyocytes. Additionally, the exosomes secreted by CaSR-stimulated PMNs had the same effect on cardiomyocytes as CaSR-stimulated PMNs, while the increased phosphorylation level of AKT in cardiomyocytes could be revered by AKT transduction pathway inhibitors. Subsequently, we identified the exosomes derived from CaSR-stimulated PMNs by second-generation sequencing technology, and increased expression of lncRNA ENSRNOT00000039868 was noted. The data show that this lncRNA can prevent the hypoxia-reoxygenation injury by upregulating the expression of PDGFD in cardiomyocytes. In vivo, exosomes from CaSR-stimulated PMNs played a significant role against AMI and reperfusion injury in myocardial tissue. Thus, we propose that exosomes derived from CaSR-stimulated PMNs can reduce I/R injury in AMI, and this effect may be related to the AKT signaling pathway.

乳腺癌是严重威胁女性健康的恶性肿瘤之一,在全球范围内,其发病率呈逐年升高以及年轻化的趋势.肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是乳腺癌肿瘤微环境中重要的免疫细胞,功能多样,具有高度的可塑性.当前的研究认为,TAMs在乳腺癌形成早期常表现为M1样表型,而在乳腺癌进展的过程中则极化为M2样表型,M2型TAMs能够促进乳腺癌的细胞增殖、血管生成、免疫抑制以及耐药性,与乳腺癌的预后呈负相关.因此,对TAMs极化方向的干预可作为乳腺癌抗癌治疗的一个新的研究方向.本文主要对乳腺癌中TAMs极化的分子机制以及对乳腺癌进展的影响进行综述.

整合素(integrin,ITG)是参与细胞与细胞外基质(extracellular matrix,ECM)黏附及细胞内外双向信号转导的跨膜糖蛋白.整合素β5(integrinβ5,ITGB5)作为整合素β亚基成员,在体内广泛表达,可在不同的生理、病理状态下发挥生物学功能.研究证实,ITGB5在肿瘤细胞和组织中的表达量显著升高,参与了肿瘤细胞增殖、迁移、侵袭、黏附等过程,并促进肿瘤血管形成及转化生长因子-β(TGF-β)诱导下的上皮-间质转化(epithelial-mesenchymal transition,EMT),是癌症形成和发生发展的关键因素.该文就ITGB5与肿瘤进展的相关研究作一综述,以期为临床肿瘤诊断、治疗及预后评价提供参考.

血小板是巨核细胞的衍生物,在止血、血栓形成和损伤修复等过程中均可发挥重要作用。同时,在肿瘤的发生发展过程中,肿瘤细胞可以诱导血小板发生活化并聚集,这一过程称为肿瘤细胞诱导的血小板聚集（TCIPA）。受肿瘤影响的血小板含有大量的活性生物分子,可以调节肿瘤细胞的血管生成,并为原发性肿瘤的转移建立一个相对适宜的转移前微环境,从而促进肿瘤的侵袭转移[1,2]。因此,了解

The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are markers of systemic inflammation. However, there is little evidence of the value of inflammation in the early diagnosis of gastric cancer (GC). A total of 2,606 patients diagnosed with GC in the past three years and 3,219 healthy controls over the same period were included in this study. Peripheral blood samples were obtained to analyze the NLR, PLR, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). The optimal cutoff levels for the NLR and PLR were defined by receiver operating characteristic (ROC) curve analysis (NLR = 2.258, PLR = 147.368). The value of different biomarkers for diagnosing GC was compared by the area under the curve (AUC). The NLR and PLR showed diagnostic sensitivity in GC (AUC = 0.715, AUC = 0.707). Using the Bonferroni correction, the NLR and PLR were superior to CEA and CA19-9 in the diagnosis of GC (P < 0.0001). The systemic inflammatory markers were significantly higher in the early stage of GC than tumor markers. After grouping patients and healthy controls by gender, we found that the diagnostic significance of combined NLR and PLR for GC was greater in male patients than in female patients (P < 0.0001). The diagnostic value of the NLR and PLR in GC is higher than that of the traditional tumor markers CEA and CA19-9. Systemic markers of inflammation are more valuable in male than female patients.

竞争性内源RNA(ceRNA)作为生物标志物、潜在的治疗靶点和强有力的预后指标,在心肌肥厚、心肌梗死以及动脉粥样硬化等心血管疾病中均表现出了巨大的研究价值及临床应用前景.该文主要介绍了ceRNA调控网络在心血管疾病(CVDs)中的最新研究成果及其调控机制.