The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ

Abstract

25 The female upper reproductive tract, including the uterus, fallopian tubes and ovaries, is 26 believed to be a sterile environment. With the improvement of bacterial detection, the 27 theory of the sterile female upper reproductive tract has been frequently challenged in 28 recent years. However, thus far, no researchers have used ovaries as study targets. Six 29 women who were diagnosed with ovarian cancer were included in the cancer group, and 30 ten women who were diagnosed with a noncancerous ovarian condition (including three 31 patients with uterine myoma and seven patients with uterine adenomyosis) were included 32 in the control group. Immunohistochemistry staining using an antibacterial 33 lipopolysaccharide (LPS) antibody was used to confirm the presence of bacteria in the 34 ovarian tissues. In addition, 16S rRNA sequencing was used to compare the differences 35 in the bacteria between ovarian cancer tissues and noncancerous ovarian tissues. BugBase 36 and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 37 (PICRUSt) were used to predict the functional composition of the bacteria. Bacterial LPS 38 was present in ovarian cancer tissue and noncancerous ovarian tissue, which implied the 39 presence of bacteria in ovarian tissue. When compared to the noncancerous ovarian 40 bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased 41 Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting 42 metagenomes, gene functions associated with the potentially pathogenic and the 43 oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. 44 Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the 45 cancer group compared to that of the control group. Different bacteria compositions were 46 present in cancerous and noncancerous ovarian tissues. 47 48 Key words: ovarian cancer; bacteria; 16S rRNA sequencing 3 49 Author summary 50 Abdominal solid viscera have always been believed to be absolutely sterile. With the 51 improvement of bacterial detection, this concept is being challenged. Researchers found 52 some bacteria existed in endometrial diseases, the question of whether the ovaries are 53 sterile is still unclear. Therefore, we assume that the bacteria in ovarian tissue are 54 associated with ovarian cancer. When compared to the noncancerous ovarian bacteria at 55 the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae 56 and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene 57 functions associated with the potentially pathogenic and the oxidative stress-tolerant 58 phenotype were enriched in the ovaries of the cancer group. Forty-six significantly 59 different KEGG pathways existed in the ovarian bacteria of the cancer group compared to 60 that of the control group. Different bacteria compositions were present in cancerous and 61 noncancerous ovarian tissues. 62 63 4 64 Introduction 65 Abdominal solid viscera, inclu...

Microbes in Tumoral In Situ Tissues and in Tumorigenesis

“…Inhibiting apoptosis, inducing the DNA damage response and increasing the susceptibility to other infections (Shanmughapriya et al, 2012); disrupt genetic stability (Kidane et al, 2014); gene members of the homologous recombination repair pathway might have frequent genetic and epigenetic alterations in ovarian cancer; the deficiency in homologous recombination repair was shown to induce genomic instability and a hyper-dependence on alternative DNA repair mechanisms and to enhance the sensitivity of double-strand break-inducing agents (Konstantinopoulos and Matulonis, 2018); the metabolic characteristics have been found to be changed in the tumors, including the enriched and reduced metabolism (Li, 2020).…”

“…In genus level, the relative abundance of Paenibacillus, Haloferula, Subdivision, Zavarzinella, Photorhabdus, Volucribacter, Blastococcus, Mesotoga, Defluviitoga, and Dorea was significantly different between cancer and control groups. Particularly, the relative abundance of Anoxynatronum sibiricum might be associated with the stage of tumor (Li, 2020). Banerjee et al used PathoChip, a very sensitive approach to detect human pathogenic microorganisms, to screen the microbes in 99 ovarian cancer samples and 20 matched (tissues adjacent to the tumor deemed to be noncancerous), as well as in 20 unmatched control samples.…”

“…As for the decreased pathways in cancer tissue, the bacteria showed the reduced alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, sulfur metabolism, biotin metabolism, protein kinase activity, biosynthesis of ubiquinone and other terpenoid-quinones, two-component system, folate biosynthesis, cell motility and secretion, citrate cycle, and ribosome biogenesis in eukaryotes. These enrichments and reductions of pathways might be the consequence of the microbial effect, which were involved in the development of cancer (Li, 2020).…”