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癌症未知原发部位患者的预后因素、临床特征(包括微生物组)及治疗结局的评估

Assessment of Prognostic Factors, Clinical Features Including the Microbiome, and Treatment Outcomes in Patients with Cancer of Unknown Primary Site

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影响因子:4.4
分区:医学3区 / 肿瘤学3区
发表日期:2024 Oct 08
作者: Karolina Dorobisz, Tadeusz Dorobisz, Katarzyna Pazdro-Zastawny
DOI: 10.3390/cancers16193416

摘要

癌症未知原发部位(CUP)是一类异质性较强的癌症,其特征为发现转移灶但无法通过现有诊断方法检测到原发肿瘤。CUP的研究尚不充分,其生物学机制尚不清楚。CUP的临床特征多样,但患者预后通常不佳,根治性治疗的可能性有限。微生物组是指寄居在人体内的微生物及其产物。近年来,借助下一代测序技术,可以评估微生物组对人体功能的影响。头颈部癌症由于局部微生物组丰富,受到微生物组的影响,菌群失调可能成为癌症发生的风险因素。本研究目的:评估CUP患者的预后因素、临床特征(包括微生物组)及治疗结局。在研究组中,检测到拟杆菌门(Bacteroides)、梭菌门(Fusobacteria)、芽孢杆菌门(Bacillota)、放线菌门(Actinomycetota)、放线菌(Actinobacteria)及Candidatus的菌群数量增加,而厚壁菌门(Firmicutes)和变形菌门(Proteobacteria)则较少。CUP发生的独立预测因子包括:白细胞计数不超过6.49×10^3/mm³、微生物组中变形菌门比例低于11.6%、厚壁菌门比例低于22.1%、放线菌门比例至少为11.0%。Porphyromonas和Fusobacterium菌群数量增加与放疗并发症风险增加及生存期缩短相关。由于缺乏共识,临床诊断和治疗CUP患者较为复杂困难。CUP患者的预后和治疗效果令人不满意。微生物组在肿瘤发生、发展及治疗中的作用逐渐受到重视,可能成为预测抗肿瘤治疗反应和并发症风险的标志。微生物组的免疫调控为改善肿瘤学治疗效果提供了研究新方向。Fusobacterium和Porphyromonas菌被认为是癌症发生的关键菌种,且会通过增加放疗并发症风险缩短患者生存期,恶化预后。而链球菌(Streptococcus)和乳酸杆菌(Lactobacillus)似乎有助于降低癌症风险、减少并发症、改善预后。全蛋白质缺乏和炎症标志物升高也是癌症风险的重要预测指标。

Abstract

cancer of unknown primary site (CUP) is a heterogeneous group of cancers in which metastases are found, and the primary tumor is not detected with available diagnostic methods. CUP is a disease that has not been fully researched, and its biology is unclear. The clinical characteristics of CUP are variable, but the prognosis of patients is usually unfavorable, and the possibilities of radical treatment are limited. The microbiome is the genes and gene products of microorganisms residing in a human body. In recent years, thanks to the use of next-generation sequencing, it is possible to assess the impact of the microbiome on human body functions. Head and neck cancers, due to the rich microbiome of this area, are influenced by it, and dysbiosis may be a risk factor for the development of cancer. Objective of this work: the aim of this study was to evaluate prognostic factors, clinical features including the microbiome, and treatment outcomes in patients with cancer of unknown primary site.in the study group, increased numbers of bacteria of the phyla Bacteroides, Fusobacteria, Bacillota, Actinomycetota, Actinobacteria, and Candidatus were detected, while Firmicutes and Proteobacteria were detected in smaller numbers. Independent predictors of CUP occurrence were the following: leukocyte count of at most 6.49 × 103/mm, bacteria from the Proteobacteria phylum in the microbiome below 11.6%, Firmicutes below 22.1%, and Actinobacteria at least 11.0%. Increased numbers of Porphyromonas and Fusobacterium bacteria were associated with the risk of radiotherapy complications and shortened survival rate.clinical diagnosis and treatment of patients with CUP is complicated and difficult due to the lack of consensus on this issue. Treatment and prognosis of patients with CUP is unsatisfactory. The clinical value of the influence of the microbiome on the development, course, and treatment of cancer is becoming increasingly important. The microbiome may become a marker of response to anticancer treatment and the risk of its complications. Immunity modulation with the microbiome provides opportunities for further research on improving the effectiveness of oncological treatment. Fusobacterium and Porphyromonas seem to be the bacteria most important for the development of cancer, also worsening the prognosis of patients by increasing the risk of complications of radiotherapy and shortening the survival rate of patients. Streptococcus and Lactobacillus seem to be bacteria that reduce the risk of cancer, reduce the risk of complications, and improve the prognosis of patients. Total protein deficiency and elevated inflammatory markers are also important predictors of cancer risk.