Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.

Response of human epidermal growth factor receptor 2-positive colorectal cancer to lapatinib monotherapy: A case report

BACKGROUND Human epidermal growth factor receptor 2(HER2)amplification is a molecular driver for a subset of colorectal cancers(CRCs)and one of the major causes of anti-epidermal growth factor receptor(EGFR)treatment failure.Compared to dual anti-HER2 treatments,which have been shown to be effective in HER2-positive metastatic CRC patients,single-agent anti-HER2 therapy is rarely used to treat CRC.CASE SUMMARY Herein,we report a case of RAS/BRAF-wild-type metastatic CRC that was identified as HER2-positive through circulating tumor DNA(ctDNA)testing by next-generation sequencing following the failure of two lines of therapy.Subsequently,the patient was given lapatinib monotherapy that led to a partial response with a progression-free survival of 7.9 mo.Moreover,serial ctDNA detection was used to monitor the efficacy of lapatinib.The aberration of HER2 copy number disappeared when radiographic assessment revealed a partial response.However,a high level of HER2 amplification was detected again at the time of disease progression.Finally,a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation was identified at the time of tumor progression,which may explain the acquired resistance to lapatinib.CONCLUSION This is the first case report of HER2-positive RAS/BRAF wild-type metastatic CRC patient responding to lapatinib monotherapy.It highlights that ctDNA testing is an effective and feasible approach to evaluate the efficacy of anti-HER2 therapy.

用于结直肠癌预后评估和精准免疫治疗的肿瘤免疫微环境转录组学分型

背景:基于免疫环境的生物学标志物或许可以指导预后评估。T细胞失活、T细胞排斥以及T细胞功能障碍均会损害肿瘤微环境进而影响免疫治疗的效果及预后。然而,截至目前尚未见利用免疫相关生物标记物来对结直肠癌患者进行分类的报道。因此,本研究旨在根据肿瘤微环境中的T细胞失活、T细胞排斥和T细胞功能障碍的程度来对结直肠癌患者进行分类。方法:通过肿瘤免疫功能障碍和排斥(TIDE)算法,对TCGA数据库中的618例结直肠癌患者的RNAseq数据和GEO数据库中的316例结直肠癌患者的基因芯片数据进行分析。采用无监督聚类法对患者进行分类。结果:基于骨髓来源抑制细胞、癌相关成纤维细胞、M2型肿瘤相关巨噬细胞、细胞毒性T细胞和PD-L1的表达,将患者聚类分为4型:1型为高度免疫功能障碍,2型为低度免疫激活,3型为强烈免疫排斥,4型为高度免疫激活、中度免疫功能障碍及中度免疫排斥。多因素Cox分析结果显示,与1型相比,2、3、4型患者总体生存的风险比(95%可信区间)分别为0.63(0.35-1.13)、0.55(0.29-1.03)和0.30(0.14-0.64)。利用GSE39582队列进行验证,也得到了相似的聚类分型和预后模式。亚组分析中,在I/II期、微卫星稳定和未接受辅助治疗的患者中,免疫聚类分型与总体生存显著相关。结论:本研究结果表明,免疫分型可作为结直肠癌患者一项可靠的预后指标,且有助于个体化免疫治疗的病例选择。