Comprehensive analysis of clinical and biological value of ING family genes in liver cancer

BACKGROUND Liver cancer(LIHC)is a malignant tumor that occurs in the liver and has a high mortality in cancer.The ING family genes were identified as tumor suppressor genes.Dysregulated expression of these genes can lead to cell cycle arrest,senescence and/or apoptosis.ING family genes are promising targets for anticancer therapy.However,their role in LIHC is still not well understood.AIM To have a better understanding of the important roles of ING family members in LIHC.METHODS A series of bioinformatics approaches(including gene expression analysis,genetic alteration analysis,survival analysis,immune infiltration analysis,prediction of upstream microRNAs(miRNAs)and long noncoding RNAs(lncRNAs)of ING1,and ING1-related gene functional enrichment analysis)was applied to study the expression profile,clinical relationship,prognostic significance and immune infiltration of ING in LIHC.The relationship between ING family genes expression and tumor associated immune checkpoints was investigated in LIHC.The molecular mechanism of ING1 mediated hepatocarcinogenesis was preliminarily discussed.RESULTS mRNA/protein expression of different ING family genes in LIHC was analyzed in different databases,showing that ING family genes were highly expressed in LIHC.In 47 samples from 366 LIHC patients,the ING family genes were altered at a rate of 13%.By comprehensively analyzing the expression,clinical pathological parameters and prognostic value of ING family genes,ING1/5 was identified.ING1/5 was related to poor prognosis of LIHC,suggesting that they may play key roles in LIHC tumorigenesis and progression.One of the target miRNAs of ING1 was identified as hsa-miR-214-3p.Two upstream lncRNAs of hsa-miR-214-3p,U91328.1,and HCG17,were identified.At the same time,we found that the expression of ING family genes was correlated with immune cell infiltration and immune checkpoint genes.CONCLUSION This study lays a foundation for further research on the potential mechanism and clinical value of ING family genes in the treatment and prognosis of LIHC.

Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma

Primary liver cancer is an important cause of cancer death,and hepatocellular carcinoma(HCC) accounts for 70%-85% of total liver cancer worldwide.Chronic hepatitis B virus(HBV) infection contributes to > 75% of HCC cases.High serum viral load is the most reliable indicator of viral replication in predicting development of HCC.HBV genotype C is closely associated with HCC in cirrhotic patients aged > 50 years,whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC.Different HBV subgenotypes have distinct patterns of mutations,which are clearly associated with increased risk of HCC.Mutations accumulate during chronic HBV infection and predict occurrence of HCC.Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction.Mutations are negatively selected by host immunity,whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis.Inflammatory pathways contribute to the inflammation-necrosis-regeneration process,ultimately HCC.Their hallmark molecules can predict malignancy in HBV-infected subjects.Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis.HBV load,genotype C,viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis.Imbalance between intratumoral CD8+ T cells and regulatory T cells or Th1 and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC.These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC,or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.

泛癌组织中T-box转录因子19基因水平与患者预后和肿瘤免疫微环境的相关性

目的基于数据库数据分析泛癌组织中T-box转录因子19(TBX19)表达水平与患者预后和肿瘤免疫微环境(免疫细胞浸润、免疫检查点基因、肿瘤突变负荷和微卫星不稳定性)之间的关系。方法从癌症基因组图谱(TCGA)数据库中获取泛癌组织及相应正常组织中TBX19表达水平,比较不同WHO分级和TNM分期泛癌组织中TBX19表达水平,使用Cox回归分析TBX19表达水平与肿瘤患者预后的关系。基于肿瘤免疫估算数据库(TIMER2)数据,采用Pearson法分析TBX19表达水平与免疫细胞浸润丰度的相关性;在Sanger Box网站中利用TCGA数据库采用Pearson方法分析TBX19表达水平与免疫评分、肿瘤突变负荷和微卫星不稳定性的相关性;基于临床生信之家数据库数据,采用Spearman法分析TBX19表达水平与免疫检查点基因的相关性。结果在膀胱尿路上皮癌、胆管癌、结肠癌(COAD)、结直肠癌(COADREAD)、食管癌、头颈鳞状细胞癌、肾透明细胞癌、肾乳头状细胞癌、混合肾癌、肝细胞癌(LIHC)、肺腺癌、肺鳞癌、嗜铬细胞瘤和副神经节瘤、直肠腺癌、胃癌、胃和食管癌癌组织中TBX19高表达(P均<0.05),在乳腺浸润癌、肾嫌色细胞癌、前列腺癌、子宫内膜癌癌组织中TBX19低表达(P均<0.05)。不同WHO分级以及TNM分期的COAD、COADREAD癌组织中TBX19表达差异有统计学意义(P均<0.05)。与TBX19低表达者比较,LIHC癌组织TBX19高表达者的总体生存期、疾病特异性生存期、无疾病间隔期和无进展间隔期短(P均<0.05)。在COAD、KIRC、LIHC等多种癌组织中,TBX19的表达与免疫细胞浸润、免疫检查点基因、肿瘤突变负荷、微卫星不稳定性密切相关(P均<0.05)。结论泛癌组织中TBX19表达水平以升高为主,TBX19高表达者预后差;癌组织中TBX19高表达与肿瘤免疫微环境有关,在多种肿瘤中免疫浸润水平升高、肿瘤突变负荷增大、微卫星不稳定性增加。

恶性胸液淋巴细胞对自体肿瘤细胞杀伤活性的研究

用不连续密度梯度离心法分离恶性胸液淋巴细胞（ＭＰＥＬ）及肿瘤细胞，比较了ＭＰＥＬ与外周血淋巴细胞（ＰＢＬ）对自体肿瘤细胞（ＡＴＣ）的杀伤活性。结果３组不同密度梯度中以１００％：６０％的密度比构成的不连续密度梯度分离效果较佳。ＰＢＬ对ＡＴＣ的杀伤活性明显高于ＭＰＥＬ（Ｐ＜０．００１），但经重组白细胞介素２（ｒＩＬ２）激活的ＭＰＥＬ的扩增能力及杀伤活性均较经ｒＩＬ２激活的ＰＢＬ（即ＬＡＫ细胞）明显为高（Ｐ＜０．００１）。表明恶性胸液患者胸腔局部免疫功能呈抑制状态，经ｒＩＬ２激活可得到改善。活化ＭＰＥＬ是较ＬＡＫ更适于肿瘤过继免疫治疗的效应细胞。