基于生物信息学数据分析ELTD1在肾透明细胞癌组织中的表达、甲基化水平及其临床意义

目的：探讨表皮生长因子蛛毒素受体7穿膜结构域蛋白1(ELTD1)在肾透明细胞癌（ccRCC）组织中的表达、甲基化水平及其与患者临床病理特征和预后的相关性。方法：通过公共数据库分析ccRCC组织中ELTD1表达和甲基化的差异水平,探讨ELTD1表达水平与患者临床病理特征和预后的相关性。通过TIMER2.0数据库评估ccRCC免疫细胞浸润,筛选ELTD1相关免疫检查点基因,进行GO功能和KEGG通路富集分析,通过基因共表达分析、筛选与ELTD1相关的基因。结果：与癌旁组织比较,ELTD1在ccRCC组织中呈高表达（P<0.05）。TCGA-KIRC队列中,ELTD1的甲基化水平与其表达呈负相关（R=-0.37,P<0.01）。ELTD1转录表达在ccRCC患者年龄、T分期、M分期、临床分期及病理分级组间存在显著差异（均P<0.01）,且高表达ELTD1与较长的OS和PFS密切相关（HR=0.55、0.63,均P<0.01）,ELTD1高表达是ccRCC的独立保护因素。ELTD1表达与B细胞、CD4+T细胞、CD8+T细胞、巨噬细胞和嗜中性粒细胞的免疫浸润呈显著负相关...     

免疫相关基因HCST对肾透明细胞癌预后的影响及其机制

目的:分析造血细胞信号转导因子(hematopoietic cell signal transducer,HCST)在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）中的表达及与ccRCC预后、免疫浸润的关系,探讨HCST对ccRCC细胞生长侵袭的影响及其作用机制。方法:利用TCGA数据库分析HCST基因在ccRCC组织中的表达水平。Cox比例风险模型分析HCST表达水平及临床特征与ccRCC患者预后的关系。肿瘤免疫评分数据库（tumor immune estimation resource,TIMER）分析ccRCC组织中HCST表达水平与免疫细胞浸润程度的相关性。体外培养ACHN细胞,分为对照组、siRNA阴性对照组和HCST siRNA组。MTT法、流式细胞实验和Transwell实验分别检测各组ACHN细胞增殖、凋亡和侵袭活性。蛋白质印迹法检测caspase-3、Bax、Bcl-2、E-cadherin、N-cadherin和Vimentin蛋白的表达。结果:与正常肾脏组织比较,HCST mRNA在ccRCC组织中的表达显著上调,且与肿瘤的分期、淋巴转移及远处转移正相关(P＜0.01)。HCST高表达、肿瘤T分期及M分期是影响 ccRCC患者预后的独立危险因素(P＜0.05)。ccRCC中HCST表达与CD8+T细胞、树突状细胞、NK细胞及Treg细胞的浸润程度正相关(P＜0.001)。与对照组比较,HCST siRNA组ACHN细胞的增殖活性、侵袭能力、Bcl-2、N-cadherin和Vimentin蛋白表达水平显著降低(P＜0.05),ACHN细胞凋亡活性、caspase-3、Bax和E-cadherin蛋白表达水平显著升高(P＜0.05)。siRNA阴性对照组与对照组比较上述各指标,差异无统计学意义(P＜0.05)。结论:HCST在ccRCC中表达上调,且与ccRCC患者的免疫浸润和预后相关。沉默HCST的表达可抑制ccRCC细胞的增殖与侵袭、促进其凋亡。     

肾透明细胞癌联合免疫治疗新策略——有氧糖酵解的研究进展及展望

肾恶性肿瘤的发病率逐年上升,其中肾透明细胞癌约占所有肾恶性肿瘤的80%,肾透明细胞癌独特的遗传背景和突变特征往往涉及以乏氧信号、糖酵解代谢、氨基酸代谢、线粒体氧化磷酸化等通路为代表的肿瘤微环境（tumor microenvironment,TME）内稳态失调。免疫检查点抑制剂（immune checkpoint inhibitor,ICI）联合酪氨酸激酶抑制剂（tyrosine kinase inhibitor,TKI）已经成为晚期肾透明细胞癌患者的一线治疗方案,但是,联合治疗方案的疗效仍有待提高,且缺乏明确诊断、指导用药、评估预后的生物标志物。近年来,多组学研究从不同层次探索肾透明细胞癌分子通路的异常改变。肾透明细胞癌发生代谢重编程,在氧气充足的情况下也以低效能的糖酵解为能量供应来源,促进自身无限生长,并且有氧糖酵解通路展现的显著异常与不良预后相关。肾透明细胞癌异常的糖酵解信号能促进肿瘤生长,并与TME中的免疫细胞相互作用,使促肿瘤免疫和抗肿瘤免疫平衡失调,造成抑制性免疫微环境,介导肿瘤免疫逃逸,从而对免疫治疗产生不利影响。因此,通过阻断异常糖代谢来抑制肿瘤生长,以有氧糖酵解通路和免疫微环境为切入点,可为肾透明细胞癌以及泛肿瘤治疗提供新的研究方向。然而,如何在复杂的肿瘤免疫微环境中最大程度地将肿瘤细胞代谢重编程转化为用药靶点并运用于临床实践仍待探讨。在肾透明细胞癌中,糖酵解抑制剂联合ICI或TKI作为新方案或能协同发挥抗肿瘤效应,逆转治疗抵抗。本文通过对糖酵解代谢途径中的关键限速酶、转运体及其抑制剂与肿瘤免疫微环境之间的关系进行综述,探讨糖酵解抑制剂在肾透明细胞癌中的作用机制和肿瘤免疫微环境的变化,及其与靶向治疗或免疫治疗联合应用的巨大临床转化价值,未来将为肾透明细胞癌的临床诊疗提供新思路,为患者带来临床获益。     

基于生物信息学分析铁死亡相关lncRNA对肾透明细胞癌组织免疫浸润和患者预后评估的意义

目的：采用生物信息学方法探索与肾透明细胞癌(ccRCC)组织中铁死亡相关的lncRNA,并探讨其与免疫细胞浸润及患者预后的相关性,为ccRCC患者提供新的分子靶点。方法：从癌症基因组图谱(TCGA)数据库下载cc RCC的转录本数据和临床数据,利用单样本基因集富集分析(ssGSEA)及相关性分析获得与铁死亡相关的lncRNA;通过单因素和多因素回归分析构建与铁死亡相关的lncRNA特征图,分析其与预后的关系;利用R软件分析铁死亡相关lncRNA与肿瘤免疫细胞浸润和药物敏感性之间的关系。构建铁死亡相关RNA网络,并通过qPCR验证中国人ccRCC组织和癌旁组织（取自2019年12月至2021年03月间在西南医科大学附属医院手术切除8例标本）中关键lncRNA的表达。结果：Kaplan-Meier分析表明,铁死亡评分高的患者总OS率低于铁死亡评分低的患者。单因素和多因素回归分析确定11个ccRCC铁死亡相关lncRNA可评估患者预后,并构建ccRCC患者1、3、5年预后预测列线图。免疫细胞浸润分析表明,铁死亡相关lncRNA与ccRCC免疫细胞浸润密切相关,其中LINC01871、PRKA...     

ANGPTL8 links inflammation and poor differentiation,which are characteristics of malignant renal cell carcinoma

Inflammation is observed in many tumors, which affects metastasis, infiltration, and immune escape and causes poor differentiation of the cancer cells. However, the molecular basis underlying the relationship between inflammation and poor differentiation in tumors has not been identified. In this study, we demonstrate that angiopoietin-like protein-8 (ANGPTL8), which is induced by stress stimuli such as inflammation, is involved in the maintenance of the undifferentiated state of clear cell renal cell carcinoma (ccRCC) cells. ANGPTL8 is also involved in the production of chemokines that attract immune suppressor cells to the tumor microenvironment. ANGPTL8 sustains the continuous production of chemokines by activating the NF-κB signaling pathway and maintains the undifferentiated state of ccRCC cells. Finally, ANGPTL8 is induced by STAT3 signaling, which is activated by immune cells in the tumor microenvironment. These results support a role for ANGPTL8 in determining the properties of ccRCC by hampering tumor cell differentiation and establishing the tumor microenvironment.     

长链非编码RNA ARAP1-AS1在肾透明细胞癌中的表达及作用研究

背景与目的：长链非编码RNA（long non-coding RNA,lncRNA）ARAP1-AS1在多种肿瘤中异常表达,但其在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）中的作用尚不清楚。探讨ARAP1-AS1在ccRCC中的生物学作用。方法：通过GEPIA数据库分析ARAP1-AS1在ccRCC组织中的表达及其与临床病理学特征及患者生存率的关系。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR）检测ccRCC组织及邻近的非肿瘤组织中ARAP1-AS1的表达水平。将患者分为ARAP1-AS1高表达组和低表达组,分析ARAP1-AS1的表达水平与患者临床病理学特征之间的关系,并进行生存分析。通过细胞计数试剂盒-8（cell counting kit-8,CCK-8）实验、transwell迁移实验及侵袭实验检测ARAP1-AS1对ccRCC细胞体外增殖、迁移及侵袭能力的影响。采用蛋白质印迹法（Western blot）检测Wnt/β-catenin信号通路相关蛋白表达变化。采用BALB/c裸小鼠移植瘤模型分析ARAP1-AS1对ccRCC细胞体内成瘤能力的影响。结果：GEPIA数据库分析结果显示,ARAP1-AS1在ccRCC中高表达,且与患者肿瘤高分期及较差的生存率相关（P均<0.05）。RTFQ-PCR显示,ARAP1-AS1在ccRCC组织及细胞系中高表达,ARAP1-AS1的高表达与肿瘤大小和分期相关（P均<0.05）。ARAP1-AS1高表达患者的总生存率较差（P<0.05）。沉默ARAP1-AS1的表达可以抑制ccRCC细胞增殖、迁移和侵袭（P均<0.05）。沉默ARAP1-AS1可以降低Wnt/β-catenin信号通路相关蛋白的表达水平（P均<0.05）。沉默ARAP1-AS1可使ccRCC细胞体内成瘤能力减弱,并使Ki-67增殖指数降低。结论：ARAP1-AS1可通过激活Wnt/β-catenin信号通路促进ccRCC的进展。     

Comprehensive immune characterization and T‐cell receptor repertoire heterogeneity of retroperitoneal liposarcoma

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas and lacks effective treatment. This study aimed to provide a thorough profile of immune characteristics of RLPS. This study included 56 RLPS patients. Multisite tumor tissues were collected from 16 patients. Immunohistochemistry was carried out to identify CD4⁺, CD8⁺, FoxP3⁺, CD20⁺, or programmed cell death‐1 (PD‐1)⁺ tumor infiltrating lymphocytes (TILs) and  Programmed cell death ligand‐1 (PD‐L1) expression in tumor tissues. Ultradeep sequencing of T‐cell receptor (TCR) β‐chain gene was carried out in 42 tumor samples as well as peripheral blood samples collected from 6 patients. In RLPS, TILs were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of TILs decreased and PD‐L1 expression increased with tumor progression. Patients with higher PD‐1/PD‐L1 expression tended to have poorer prognosis, whereas patients with tertiary lymphoid structure tended to have a favorable disease‐free survival. Although T‐cell clones in tumors were quite different from those in peripheral blood, TCR sequencing showed low TCR repertoire reads as well as polyclonal status within tumors, which indicated limited T cell response in the tumors. Both TILs distribution and TCR repertoires suggested spatial immune heterogeneity in RLPS. Our research described the immune landscape of RLPS, and suggested RLPS might be a kind of tumor with low T cell infiltration as well as great immune heterogeneity. Therefore, strategies that can facilitate lymphocytic infiltration and immune reactivity need to be developed in the future to improve the efficacy of immunotherapy.     

Increased apoptosis is associated with robust immune cell infiltration and cytolytic activity in breast cancer

Tumor infiltrating immune cells plays a critical role in cancer progression. Apoptosis is an autonomous cell death that counteracts tumor growth. To this end, we hypothesized that increased apoptosis in breast cancer is associated with immune cell killing. Apoptosis score of MSigDB Hallmark collection was used to analyze METABRIC cohort (n=1904) and TCGA (n=1069) as validation cohort. High apoptosis tumors enriched cancer promoting signaling pathways; hypoxia, KRAS, TGF-β, PI3K signaling, and was associated with low MKI67 expression and less cell proliferation gene sets, less homologous recombination defects, and less altered fraction. High apoptosis tumors also enriched angiogenesis and high infiltration of vascular endothelial cells, pericytes and stromal cells and significantly enriched inflammation and immune response-related gene sets and high infiltration of CD8, CD4 memory, dendritic cells, M1 and M2 macrophages and significant elevation of cytolytic activity and immune checkpoint molecules, consistently in both cohorts. In conclusion, breast cancer patients with high apoptosis are associated with angiogenesis, immune response, high immune cell infiltration and cytolytic activity. To the best of our knowledge, this is the first study to utilize in silico translational approach to demonstrate the clinical relevance of apoptosis in breast cancer patients in large cohorts.     

MUC20 as a novel prognostic biomarker in ccRCC correlating with tumor immune microenvironment modulation

Tumor microenvironment (TME) broadly participates in genesis development of clear cell renal cell carcinoma (ccRCC). To recognize the immune and stromal modulation in TME, we screened the differentially expressed TME-related genes generated by the ESTIMATE algorithm in ccRCC specimens. Following the construction of protein-protein interaction (PPI) network and univariate COX regression, mucin 20 (MUC20) was judged to be a predictive factor. Further analysis, including immunohistochemistry (IHC) showed that MUC20 was positively correlated with survival and negatively correlated with the clinicopathologic characteristics (grade, clinical and TNM stages) in ccRCC patients. Gene Set Enrichment Analysis suggested that the low-expression MUC20 group was primarily enriched in immune-related activities, inflammation and epithelial-mesenchymal transition. Based on the CIBERSORT analysis for tumor-infiltrating immune cells (TICs), MUC20 was positively correlated with CD8⁺ T cells and resting mast cells and negatively correlated with activated CD4⁺ memory T cells, Treg cells, and plasma cells, implying that MUC20 may contribute to immune component in TME. Additionally, the patients with low MUC20 expression had better response to immune checkpoint blockades (ICBs) and 17 potential anticancer drugs were screened regarding calculating IC₅₀ value. Thus, MUC20 may contain a value of prognosis assessment for ccRCC patients and indicate the immune modulation status of TME, which provided a novel insight for comprehensive immunotherapy.     

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer

Recent studies have reported that tumor‐infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine‐based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine‐based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM‐activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell‐related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine‐based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.     

基于TCGA 数据库分析DTX2 在肾透明细胞癌组织中表达的临床意义及其对肾癌细胞增殖、迁移与侵袭的影响

目的：基于TCGA数据库分析Deltex E3泛素连接酶2(DTX2)在肾透明细胞癌（ccRCC）组织中的表达水平及临床意义,探讨DTX2对ccRCC细胞增殖、迁移和侵袭的影响。方法：利用TIMER数据库分析DTX2在泛癌组织中的表达水平,通过UALCAN数据库进一步验证ccRCC组织和癌旁组织中DTX2 mRNA和蛋白表达差异。使用UALCAN数据库中的TCGAccRCC队列数据集,分析ccRCC中DTX2表达与患者临床病理特征的相关性。通过K-M plot数据库分析DTX2表达与cc RCC患者预后的相关性。利用DAVID数据库对DTX2相关基因进行GO和KEGG通路富集分析。通过qPCR法检测DTX2基因在人胚肾293(HEK293)细胞和ccRCC细胞A498、Caki-1中的表达水平。利用siRNA技术分别将DTX2 siRNA及其阴性对照质粒转入A498、Caki-1细胞,采用CCK-8法、平板克隆实验、划痕实验及Transwell侵袭实验分别检测敲低DTX2对细胞增殖、迁移和侵袭的影响。结果：TCGA数据库分析结果表明,与癌旁组织相比,ccRCC组织中DTX2 mRNA和...     

RBM4 inhibits the growth of clear cell renal cell carcinoma by enhancing the stability of p53 mRNA

RBM4 has been reported as a tumor suppressor gene in cancers, including lung cancer, colon cancer and gastric cancer. However, the role of RBM4 in clear cell renal cell carcinoma (ccRCC) remains unclear. Therefore, the present study investigated the expression and biological function of RBM4 in ccRCC. Analysis of the differential expression of RBM4 and its relationship with clinicopathological features using ccRCC samples data from TCGA database deminstrated that RBM4 expression in tumor samples of ccRCC was lower than that in normal samples, and RBM4 expression was closely related to the survival time of patients. RBM4 overexpression (RBM4-oe) cell lines were constructed to investigate the effect of RBM4 on biological function using CCK-8, EdU, flow cytometry and wound-healing assays. In addition, the regulatory effect of RBM4 on signaling pathways was investigated by GSEA and WB assays. RBM4-oe significantly reduced the proliferation of ccRCC cells by controlling the p53 signaling pathway, inhibited cell cycle progression and promoted apoptosis. In addition, RBM4-oe suppressed the migration and invasion of cells by EMT. Mechanistically, RBM4-oe facilitated the activity of the p53 signaling pathway by enhancing the stability of p53 mRNA. Finally, RBM4-oe markedly inhibited the growth of tumors formed with 786-O cells in vivo. In summary, there findings suggeated that RBM4 inhibits the progression of ccRCC by promoting p53 signaling pathway activity by enhancing the stability of p53 mRNA, suggesting that RBM4 may be a potential target for the treatment of patients.     

The renal clear cell carcinoma immune landscape

A comprehensive evaluation of the clear cell renal cell carcinoma (ccRCC) immune landscape was found using 584 RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), we identified 17 key dysregulated immune-associated genes in ccRCC based on association with clinical variables and important immune pathways. Of the numerous findings from our analyses, we found that several of the 17 key dysregulated genes are heavily involved in interleukin and NF-kB signaling and that somatic copy number alteration (SCNA) hotspots may be causally associated with gene dysregulation. More importantly, we also found that key immune-associated genes and pathways are strongly upregulated in ccRCC. Our study may lend novel insights into the clinical implications of immune dysregulation in ccRCC and suggests potential immunotherapeutic targets for further evaluation.     

EFHD1, a novel mitochondrial regulator of tumor metastasis in clear cell renal cell carcinoma

The biological function of many mitochondrial proteins in mechanistic detail has not been well investigated in clear cell renal cell carcinoma (ccRCC). A seven-mitochondrial-gene signature was generated by Lasso regression analysis to improve the prediction of prognosis of patients with ccRCC, using The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium cohort. Among those seven genes, EFHD1 is less studied and its role in the progression of ccRCC remains unknown. The decreased expression of EFHD1 was validated in clinical samples and was correlated with unfavorable outcome. Overexpression of EFHD1 in ccRCC cells resulted in the reduction of mitochondrial Ca²⁺, and the inhibition of cell migration and invasion in vitro and tumor metastasis in vivo. Mechanistically, EFHD1 physically bound to the core mitochondrial calcium transporter (mitochondrial calcium uniporter, MCU) through its N-terminal domain. The interaction between EFHD1 and MCU suppressed the uptake of Ca²⁺ into mitochondria, and deactivated the Hippo/YAP signaling pathway. Further data revealed that the ectopic expression of EFHD1 upregulated STARD13 to enhance the phosphorylation of YAP protein at Ser-127. The knockdown of STARD13 or the overexpression of MCU partly abrogated the EFHD1-mediated induction of phosphorylation of YAP at Ser-127 and suppression of cell migration. Taken together, the newly identified EFHD1–MCU–STARD13 axis participates in the modulation of the Hippo/YAP pathway and serves as a novel regulator in the progression of ccRCC.     

头颈部鳞状细胞癌中免疫细胞浸润模式与预后的相关性分析

目的:研究免疫细胞浸润模式在头颈部鳞状细胞癌(HNSCC)中的特点,探讨肿瘤浸润性免疫细胞与肿瘤预后的关系。方法:通过CIBERSORT软件计算分析肿瘤样本的基因表达谱数据,利用Kaplan-Meier方法计算浸润性免疫细胞水平与总生存期之间的关系。结果:从TCGA数据库下载HNSCC组织403例、正常样品31例的数据,经过CIBERSORT软件分析获得免疫细胞占比,经过校正后得到345例HNSCC肿瘤组织和6例正常样品的免疫细胞组成矩阵,通过Kaplan-Meier方法分析显示:嗜酸性粒细胞构成比高的患者生存期短;γδT细胞和调节性T细胞构成比高的患者生存期更长。结论:对于不同分期和分级的HNSCC患者,浸润性免疫细胞的组成存在较大的差异;嗜酸性粒细胞、γδT细胞和调节性T细胞的含量高低可以作为HNSCC的重要预后因素。     

Warburg phenotype in renal cell carcinoma: High expression of glucose‐transporter 1 (GLUT‐1) correlates with low CD8+ T‐cell infiltration in the tumor

Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen (“Warburg Effect”). Here, we analyzed for the first time a possible link between glucose metabolism and immune cell infiltration in renal cell carcinoma (RCC). RCC specimens revealed a highly significant increase in the expression of lactate dehydrogenase A (LDHA) and glucose‐transporter 1 (GLUT‐1) compared to the corresponding normal kidney tissue on mRNA level. Accordingly, tumor cell lines of different origin such as RCC, melanoma and hepatocellular carcinoma strongly expressed LDHA and GLUT‐1 compared to their nonmalignant counterparts. In line with this finding, tumor cells secreted high amounts of lactate. High expression of GLUT‐1 and LDH5, a tetramer of 4 LDHA subunits, was confirmed by tissue microarray analysis of 249 RCC specimens. Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma showed a constitutive, but heterogeneous expression of GLUT‐1 and LDH5, respectively. The number of CD3⁺, CD8⁺ and FOXP3⁺ T cells was significantly elevated in RCC lesions compared to normal kidney epithelium, but effector molecules such as granzyme B and perforin were decreased in tumor infiltrating T cells. Of interest, further analysis revealed an inverse correlation between GLUT‐1 expression and the number of CD8⁺ T cells in RCC lesions. Together, our data suggest that an accelerated glucose metabolism in RCC tissue is associated with a low infiltration of CD8⁺ effector T cells. Targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches in RCC.     

血清IL-22在肾透明细胞癌患者预后分析中的应用价值

目的:研究IL-22在肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）患者血清中的表达情况、临床意义及其在患者预后分析中的应用价值。方法:收集168例ccRCC患者的血清,同时以30例健康志愿者血清作为对照。采用ELISA法检测两组对象血清IL-22的表达水平。生存分析探讨IL-22表达水平与患者预后情况的关系。Cox比例风险模型分析影响患者生存时间的危险因素。结果:ccRCC患者血清中的IL-22水平明显高于健康志愿者。对ccRCC患者随访5~63个月,平均（45±12.4）个月,IL-22高水平组的无进展生存率及总体生存率明显低于低水平组。多因素分析结果表明,血清IL-22表达水平、肿瘤直径、肿瘤分化程度及肿瘤TNM分期是影响ccRCC患者生存期的独立危险因素。结论:ccRCC患者血清IL-22表达水平偏高,且IL-22高水平表达患者预后较差。血清IL-22表达水平在ccRCC患者的预后判断中具有较好的应用价值。     

Comprehensive co-expression analysis reveals TMC8 as a prognostic immune-associated gene in head and neck squamous cancer

The occurrence and prognosis of head and neck squamous cell cancer (HNSC) is closely associated with human papillomavirus (HPV) infection. Transmembrane channel-like 8 (TMC8) is a key gene affecting the susceptibility of HPV and that plays an important role in T cell regulation. However, the mechanism by which TMC8 affects T cells and whether it further affects the prognosis of patients with HNSC remains unclear. In the present study, oral cancer cell lines and independent tumor specimens were used to detect TMC8 expression in HNSC. Differential expression of TMC8, methylation status, function and associated signaling pathways were further analyzed. Then, multiple databases were cross-analyzed for the relationship of TMC8 with immune cell infiltration and its impact on the prognosis of numerous types of cancer. The results showed that TMC8 was upregulated in HNSC and high expression was predictive of an improved prognosis. Furthermore, TMC8 was concentrated in multiple immune-associated signaling pathways and the expression of TMC8 was associated with the infiltration of CD4⁺ T cells and their subsets, including CD8⁺ T cells, B cells and macrophages, suggesting that TMC8 may play an anti-HPV role by regulating CD4⁺ T cells. Thus, TMC8 plays an anti-HPV role by regulating the infiltration level of CD4⁺ T cells, and could therefore be used as a potential prognostic marker for patients with HNSC.