HPV相关的头颈部鳞状细胞癌的研究进展

随着吸烟、饮酒危险因素的相应控制,头颈部鳞状细胞癌的发病率有所下降,但是一部分由高危型HPV16/18感染引起的头颈部鳞癌的发病率却呈明显的上升趋势。HPV相关的头颈部鳞癌因特殊的致病因素而表现出独特的基因表达谱和生物学特性,且对放化疗敏感、预后良好以及有更高的生存率,因此治疗方式也有区别于其他头颈部鳞癌。本文就近些年来关于HPV相关的头颈部鳞癌流行病学特点、致癌机制以及诊断与防治作一综述。     

头颈部鳞状细胞癌肿瘤微环境的研究进展

肿瘤微环境在头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)等多种癌症中已得到广泛研究,其各组成部分对肿瘤的预后有重要指示意义,并直接指导肿瘤的治疗策略。该文综述了HNSCC微环境中各组成成分与肿瘤的相互作用关系,包括免疫细胞如中性粒细胞、巨噬细胞及T细胞,以及免疫检查点PD-1/PD-L1。     

头颈部鳞状细胞癌巨噬细胞关键基因的筛选分析

目的 应用生物信息学的方法分析筛选头颈部鳞状细胞癌(HNSCC)巨噬细胞中的潜在关键基因,为HNSCC的预后提供靶点。方法 基于在线数据库,利用一致流形近似与投影(UMAP)降维,捕获巨噬细胞群;进一步通过t-分布随机近邻嵌入(tSNE)聚类降维分析肿瘤组织与正常组织细胞群分布的变化并筛选差异基因的表达;运用Monocle包对关键风险基因在不同发育阶段细胞中的表达情况进行分析;利用Kaplan-Meier Plotter在线数据平台分析生存曲线;运用空间转录组技术验证关键基因在组织中的表达映射;多色荧光免疫组化进行临床样本的验证。结果 捕获得到7个巨噬细胞亚群,其中第1亚群仅存在于肿瘤组织中且分泌型磷蛋白1(SPP1)基因高富集。SPP1高表达趋向巨噬细胞M2型极化并处于细胞分化的终末阶段。SPP1+巨噬细胞糖酵解、缺氧、上皮间质化、血管生成等功能活跃,与HNSCC患者的预后呈负相关。结论 SPP1可能成为HNSCC中有价值的预后生物标志物。     

肺鳞状细胞癌预后标志物ACE2和免疫相关

目的：血管紧张素转换酶2(ACE2)与非小细胞肺癌进展有关。然而,ACE2在肺鳞状细胞癌（LUSC）患者预后和免疫中的作用尚未阐明。方法：通过UALCAN、TCGA、TISIDB等数据库分析ACE2在LUSC组织中的表达,及其在LUSC进展和免疫中的作用价值。结果：ACE2在LUSC组织中低表达。ACE2低表达与LUSC患者种族、癌症分期、吸烟史、组织学亚型和免疫学亚型相关。ACE2高表达的LUSC患者预后较好。基因富集分析显示ACE2可能通过药物代谢酶、TGF-β信号通路、ECM受体相互作用等途径参与LUSC进展。ACE2表达水平与LUSC免疫浸润细胞、免疫激活分子、免疫抑制分子、MHC分子、趋化因子及其受体分子水平相关。结论：ACE2有望成为LUSC患者预后的生物标志物,且与LUSC免疫相关。     

原发性和继发性甲状腺鳞状细胞癌的诊治分析

目的探讨原发性甲状腺鳞状细胞癌(PSCCT)和继发性甲状腺鳞状细胞癌(SSCCT)的临床特点。方法对北京协和医院收治的17例PSCCT患者和6例SSCCT患者的病例资料进行系统回顾。分析、比较两组患者的临床症状、超声及病理特征。结果女性的发病率高于男性,平均年龄在56岁左右。两组患者最常见的主诉均为颈部肿块。SSCCT组咳嗽的比例高于PSCCT组(P0.01)。PSCCT组肿瘤的平均大小高于SSCCT组(P0.05)。甲状腺乳头状癌(PTC)可同时伴发PSCCT。PSCCT患者平均生存时间为17.1个月,SSCCT患者平均生存时间为13.5个月。可以通过年龄、颈部淋巴结肿大、根治手术、PTC来预测PSCCT患者总体生存率。结论 SCCT具有侵袭性,颈部肿块往往是最常见的主诉。PTC可合并或复发为PSCCT。年龄、颈部淋巴结肿大、根治手术、PTC是PSCCT患者总体生存期(OS)的预测因子。     

头颈部鳞状细胞癌组织中人乳头状瘤病毒的检测及其意义

人乳头状瘤病毒 (humanpapillomavirus,HPV)是一种致瘤性DNA病毒 ,已被普遍公认为人类生殖道肿瘤的重要致病因素。近年来 ,HPV与人类头颈部肿瘤 ,尤其是与头颈部鳞癌的关系日益被人们所重视和研究 ,被认为是继吸烟、饮酒之后的头颈部鳞癌的第三大致病因素。大量研究证实 ,HPV在人类头颈部鳞癌 ,如 :扁桃体癌、舌癌及喉癌原发肿瘤中检出率高 ,而在鼻咽癌中阳性率较低。另外 ,HPV在头颈部鳞癌转移淋巴结中的检测未见报道。基于以上特点 ,本研究试图通过对头颈部不同原发部位的鳞癌转移淋巴结中HPV的检测 ,来探讨借助HPV检测在鉴别原…     

卵巢原发性鳞状细胞癌15例临床病理学特征及预后分析

目的探讨卵巢原发性鳞状细胞癌(POSCC)的临床病理学特征及预后。方法收集2009年1月至2018年12月中国科学院大学附属肿瘤医院诊治的15例卵巢原发性鳞状细胞癌, 通过免疫组织化学法检测p16、hMLH1、hMSH2、hMSH6、PMS2在POSCC中的表达, RNAscope原位杂交技术检测POSCC中18种高危型人乳头状瘤病毒(HPV)。结果 15例病例中可见不同分化程度的鳞状细胞癌, 包括高分化3例, 中-低分化12例。肿瘤周围4例可见原位鳞状细胞癌, 4例可见畸胎瘤成分, 1例可见子宫内膜样癌/不典型增生成分, 1例可见子宫内膜异位腺体。5例(5/15)p16表达阳性且原位杂交证实有高危型HPV感染, 其余10例p16阴性病例原位杂交均未检测到高危型HPV感染。所有病例均无错配修复蛋白缺失。与无感染HPV患者相比, 伴有高危型HPV感染患者的总生存时间(P=0.038)及无进展生存时间(P=0.045)较长。结论 POSCC多见于绝经后女性, 常为单侧发生, 血清学指标CA125及鳞状细胞癌抗原(SCC)上升最常见。形态学上肿瘤呈现不同的分化程度, 但目前的数据表明分化程度...     

腺样鳞状细胞癌12例临床病理分析

１２例发生于外阴、阴茎、眼睑结膜、口腔、鼻腔、头部及下肢的腺样鳞癌病人中，男女各６人，年龄２４－７３岁，平均５８．４岁。肿瘤由角化鳞癌细胞形成的腺样结构和实性癌组织组成，均有广泛或较广泛的浸润，但有区域淋巴结转移者仅１例。局部扩大切除术治疗可有良好效果，此癌发生可能与普通鳞癌组织的变态性分化有关。     

头颈部鳞状细胞癌肿瘤微环境中细胞成分研究进展

肿瘤微环境是头颈部鳞状细胞癌中复杂的微生态系统, 微环境中各种细胞直接作用于肿瘤细胞或是通过分泌细胞因子影响下游信号转导通路促进/抑制肿瘤细胞, 在头颈部鳞状细胞癌的发生、发展中发挥着至关重要的作用, 也为未来头颈部鳞状细胞癌的诊治提供新思路。     

PD-1 Haplotype Combinations and Susceptibility of Patients to Squamous Cell Carcinomas of Head and Neck

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of head and neck and the sixth most common malignancy worldwide. Programmed cell death 1 (PD-1) is an immune inhibitory molecule which through interaction with its ligands recruits protein phosphatase resulting in immune response inhibition. Expression of PD-1 ligands on tumor cells is considered as one of the crucial immune evasion mechanisms. This study aimed to investigate the association of PD-1 gene polymorphisms at positions PD1.3 (rs11568821), PD1.5 (rs2227981) and PD1.9 (rs2227982) with susceptibility to HNSCCs.

Subjects and methods: 150 patients pathologically confirmed to suffer from HNSCCs and 150 age-sex matched healthy controls were recruited in this study. Genomic DNA was extracted from white blood cells of all participants. Restricted fragment length polymorphisms (RFLP)-PCR was performed using site specific primers to determine the genotypes in each position.

Results: Statistical analyses indicated no significant differences in the frequencies of genotypes, alleles as well as haplotypes between patients and controls (P > 0.05), however, haplotype combination differed significantly between two groups. GCC/GCT, GCC/GCC and GCT/GCC were higher in the HNSCC patients than the control group (P < 0.05). On the other hand, in the controls, GCT/GCT, GCT/ACC, GCT/ACT and ACC/GCT were more frequent. No significant association was found with various HNSCC clinicopathological characteristics.

Discussion: Our results suggested that although PD-1 gene polymorphisms at three investigated positions are not solely associated with susceptibility to HNSCCs, haplotype combinations emerged from these three loci may render susceptibility.     

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms.Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis.Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells.Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.     

Correlation of Choline/Creatine and Apparent Diffusion Coefficient values with the prognostic parameters of Head and Neck Squamous Cell Carcinoma

The aim of this study was to measure choline/creatine (Ch/Cr) levels through ¹H‐MRS and apparent diffusion coefficient (ADC) values through diffusion‐weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved this study and informed written consent was obtained from all study participants. A prospective study of 43 patients (31 men and 12 women; mean age, 65 years) with HNSCC was conducted. Single‐voxel ¹H‐MRS was performed at the tumor or metastatic cervical lymph node with point‐resolved spectroscopy (PRESS) at TE = 135 ms. Diffusion‐weighted MR images with b values of 0, 500 and 1000 s/mm² and contrast MRI of the head and neck were performed. The Ch/Cr levels and ADC values of HNSCC were calculated. The gross tumor volume (GTV) was also calculated. The degree of tumor differentiation was determined through pathological examination. The HNSCC Ch/Cr level was negatively correlated with the ADC value (r = ?0.662, p = 0.001). There was a significant difference in the Ch/Cr and ADC values at different degrees of tumor differentiation (p = 0.003 and p = 0.001) and with different GTVs (p = 0.122 and p = 0.001). The following prognostic parameter categories were used: (i) poorly differentiated and undifferentiated versus well differentiated to moderately differentiated; and (ii) HNSCC with GTV < 30 cm³ versus GTV > 30 cm³. The cut‐off values for Cho/Cr and ADC for each category were 1.83, 0.95 and 1.94, 0.99, respectively, and the areas under the curve were 0.771, 0.967 and 0.726, 0.795, respectively, for each category. We conclude that the Ch/Cr levels determined using ¹H‐MRS and the ADC values are well correlated with several prognostic parameters of HNSCC. Copyright © 2016 John Wiley & Sons, Ltd.     

食管鳞癌组织中miRNAs差异表达谱的筛选及研究

目的 筛选并鉴定在食管鳞癌（ESCC）及癌旁组织中miRNAs的差异表达,为进一步阐明其在ESCC发病机制中的作用奠定基础。方法 选取在邯郸市第一医院行食管癌切除术患者新鲜的鳞癌组织及癌旁正常组织,各3例,抽提总RNA,利用miRNAs芯片筛选其中差异表达的miRNAs,并对miR-106b-3p通过进一步RT-qPCR 技术进行验证。结果 miRNAs芯片从配对组织中共筛检出62个差异表达的miRNAs,其中41个miRNAs表达上调,21个miRNAs表达下调,鳞癌组织与癌旁正常组织中差异表达的miRNAs比较,差异有统计学意义（P＜0.05）。miR-106b-3p在ESCC组织中的表达高于癌旁组织,差异有统计学意义（P＜0.05）,与芯片结果一致。结论 食管鳞癌组织中miRNAs的差异表达为进一步研究miRNAs在ESCC发病中的作用奠定了基础;miR-106b-3p的高表达可能与ESCC的发生、发展有关。     

VAV3蛋白在喉鳞状细胞癌中的表达及作用机制

目的 研究VAV3蛋白在喉鳞状细胞癌组织中的表达情况,及其对喉癌临床分型、淋巴转移等影响,分析其可能的机制.方法 利用免疫组织化学方法检查VAV3蛋白在喉鳞状细胞癌组织及喉部非癌组织中的表达,检测VAV3蛋白对喉鳞状细胞癌侵袭,淋巴转移等影响.结果 VAV3蛋白在喉鳞状细胞癌组织中表达为69.76％,在喉部非癌组织中的表达为10％,前者明显高于后者,差异有统计学意义(x2=11.937,P=0.001).它的表达与临床分型、T分型及淋巴结转移有统计学意义(P＜0.05),与性别、年龄、吸烟、分型之间无统计学意义(P＞0.05).结论 VAV3蛋白在喉癌组织中高表达,且可促进喉癌组织侵袭、转移能力.VAV3蛋白高表达,可作为判断喉癌及预后的一种新的分子标志.     

头颈部鳞癌干细胞标志物的研究进展

肿瘤干细胞(CSC)是一群具有自我更新能力和多向分化潜能的肿瘤细胞,虽然CSC在肿瘤细胞总数中只占很小比例,但在肿瘤的起源、发展、转移及复发等方面均有重要的作用.过去几年内研究者已经证明包括头颈部鳞癌干细胞在内的许多CSCs的存在,并分别针对头颈部肿瘤干细胞与头颈部鳞癌的关系、肿瘤干细胞的生物学特性和鉴定标志等问题展开...     

Tumor Mutation Burden,Immune Cell Infiltration,and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors.Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model.Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis.Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635.Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.     

The fibroblast growth factor receptor 4 (FGFR4) Arg388 allele correlates with survival in head and neck squamous cell carcinoma

BACKGROUND: The increased expression of the fibroblast growth factor receptor 4 (FGFR4) has been identified in many human cancers. Recently, a single nucleotide polymorphism changing the sense codon 388 from glycine to arginine was identified in the FGFR4 gene. The FGFR4 Arg(388) allele was found to be associated with a poor prognosis for positive node breast cancer, high-grade soft-tissue sarcoma, colon carcinoma, and head and neck squamous cell carcinoma (HNSCC). METHODS: We decided to verify the impact of the FGFR4 Arg(388) allele on survival as well as its association with histoclinical data in 75 cases of HNSCC. The FGFR4 Arg(388) allele was detected by PCR-RFLP and DNA sequencing. RESULTS: The FGFR4 Arg(388) allele was detected in 42.5% of the tumors (37% heterozygous Gly/Arg and 5.5% homozygous Arg/Arg). The presence of at least one Arg allele was significantly correlated with reduced overall survival after 24 months of follow-up. The cases involving the Arg allele presented an increased mortality risk of 2.2 if compared to the non-carrier cases. CONCLUSION: The FGFR4 Arg(388) allele is associated with a shortened survival.