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      Altered microbial diversity and composition of multiple mucosal organs in cervical cancer patients

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          Abstract

          Objectives

          The aim of this study was to characterize the microbiome of multiple mucosal organs in cervical cancer (CC) patients.

          Methods

          We collected oral, gut, urinary tract, and vaginal samples from enrolled study participants, as well as tumor tissue from CC patients. The microbiota of different mucosal organs was identified by 16S rDNA sequencing and correlated with clinical-pathological characteristics of cervical cancer cases.

          Results

          Compared with controls, CC patients had reduced α-diversity of oral and gut microbiota ( p Oral_Sob < 0.001, p Oral_Shannon = 0.049, p Oral_Simpson = 0.013 p Fecal_Sob = 0.030), although there was an opposite trend in the vaginal microbiota ( p Vaginal_Pielou = 0.028, p Vaginal_Simpson = 0.006). There were also significant differences in the β-diversity of the microbiota at each site between cases and controls ( p Oral = 0.002, p Fecal = 0.037, p Urine = 0.001, p Vaginal = 0.001). The uniformity of urine microbiota was lower in patients with cervical squamous cell carcinoma ( p Urine = 0.036) and lymph node metastasis ( p Urine_Sob = 0.027, p Urine_Pielou = 0.028, p Urine_Simpson = 0.021, p Urine_Shannon = 0.047). The composition of bacteria in urine also varied among patients with different ages ( p = 0.002), tumor stages ( p = 0.001) and lymph node metastasis ( p = 0.002). In CC cases, Pseudomonas were significantly enriched in the oral, gut, and urinary tract samples. In addition, Gardnerella, Anaerococcus, and Prevotella were biomarkers of urinary tract microbiota; Abiotrophia and Lautropia were obviously enriched in the oral microbiota. The microbiota of tumor tissue correlated with other mucosal organs (except the gut), with a shift in the microflora between mucosal organs and tumors.

          Conclusions

          Our study not only revealed differences in the composition and diversity of the vaginal and gut microflora between CC cases and controls, but also showed dysbiosis of the oral cavity and urethra in cervical cancer cases.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12885-024-12915-1.

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          Most cited references44

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            The human tumor microbiome is composed of tumor type–specific intracellular bacteria

            Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.
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              Current understanding of the human microbiome

              Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.
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                Author and article information

                Contributors
                lizheng@kmmu.edu.cn
                zhanglan@kmmu.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                17 September 2024
                17 September 2024
                2024
                : 24
                : 1154
                Affiliations
                [1 ]GRID grid.517582.c, ISNI 0000 0004 7475 8949, Department of Radiation Oncology, , The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), ; 519 Kunzhou Road, Xishan District, Kunming, 650118 China
                [2 ]GRID grid.517582.c, ISNI 0000 0004 7475 8949, Department of Radiology, , The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), ; 519 Kunzhou Road, Xishan District, Kunming, 650118 China
                [3 ]GRID grid.517582.c, ISNI 0000 0004 7475 8949, Department of Gynecologic Oncology, , The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital, Yunnan Cancer Center), ; 519 Kunzhou Road, Xishan District, Kunming, 650118 China
                Article
                12915
                10.1186/s12885-024-12915-1
                11409810
                39289617
                4e0ead06-34ed-4188-a73b-e13310af5fcb
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 26 November 2023
                : 9 September 2024
                Funding
                Funded by: Yunnan Fundamental Research Projects
                Award ID: 202201AT070009
                Funded by: Innovative Research Team of Yunnan Province
                Award ID: 202305AS350020
                Award ID: 202305AS350020
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82160562
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Oncology & Radiotherapy
                cervical cancer,16s rdna sequencing,multi-organ microbiome,dysbiosis
                Oncology & Radiotherapy
                cervical cancer, 16s rdna sequencing, multi-organ microbiome, dysbiosis

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