Analysis of the Impact of the Presence of Phylum Cyanobacteria in the Microbiome of Patients with Breast Cancer on Their Prognosis

Abstract

Cyanobacterial blooms caused by Cyanobacteria adversely affect the health of the people living in their vicinity. We elucidated the effect of Cyanobacteria in patients with breast cancer. The serum microbiome of the patients with breast cancer was analyzed using NGS. Serologic tests were performed to analyze the association between the factors affecting the liver function of patients with breast cancer and the amount of Cyanobacteria. In addition, the recurrent-free survival of patients with breast cancer according to the abundance of Cyanobacteria was analyzed. The abundance of Cyanobacteria tended to be correlated with the serological results related to liver function. A high abundance of Cyanobacteria seemed to be more related to late-stage breast cancer. A high recurrent-free survival was related to a low abundance of Cyanobacteria. Even though no toxicity study was conducted, this study demonstrates the impact of phylum Cyanobacteria on the prognosis of patients with breast cancer. Thus, the abundance of Cyanobacteria in the microbiome can help predict the prognosis of patients with breast cancer.

Keywords: Cyanobacteria; breast cancer; microbiome; prognostic factor.

Figure 1

Analysis of the cyanobacterial blooms in Republic of Korea, according to the Sentinel-2 satellite data. (a) Data showing the cyanobacterial blooms near Eulsukdo, in the Nakdong River estuary, (b) in the Han River, (c) in the Geum River estuary, (d) and in the Ganwol Lake, an artificial lake in Cheonsu Bay. The color indicates the level of cyanobacterial blooms; the red color shows the most severe cyanobacterial blooms, and the black color shows that there are no cyanobacterial blooms in the freshwater.

Figure 2

A 10 × 10 dot plot graph resulting from the analysis of the microbiome of patients with breast cancer at the phyla level, showing the relative proportion of phylum Cyanobacteria (red arrow) in their microbiome. P: phylum.

Figure 3

The level of the phylum Cyanobacteria in each group of patients with breast cancer. The relative proportion of phylum Cyanobacteria in patients with recurrence-free and recurrence states was compared. RF: patients without recurrence during more than 6 years of follow-up; R: patients with recurrence during more than 6 years of follow-up; RF-R: mean difference in phylum Cyanobacteria between the two patient groups.

Figure 4

Bar graphs showing the relationship between the presence or absence of Cyanobacteria in the microbiome and the characteristics of the patients with breast cancer. (a) Percentage of patients according to cancer stage. (b) Percentage of patients according to menopause or not. (c) Percentage of patients according to eating habits. (d) The average age according to the presence or absence of Cyanobacteria. (e) The average BMI according to the presence or absence of Cyanobacteria. (f) The average Ki67 index according to the presence or absence of Cyanobacteria. (g) The number of lymph node metastases according to the presence or absence of Cyanobacteria. (h) Tumor size according to the presence or absence of Cyanobacteria. (i) Nuclear grade according to the presence or absence of Cyanobacteria. PMP: premenopausal patients; MP: patient with menopause; NR: nonresponse; Vegetarian: patients who eat only vegetarian food; Meat-based diet: patients who eat meat-based foods daily; Omnivorous: patients who eat any food well; NR: nonresponse; BMI: body mass index; LN: lymph node; (N): number of patients.

Figure 5

The relationship between the proportion of phylum Cyanobacteria in the microbiome of patients and their serology results or eating habits. The proportion of Cyanobacteria according to (a) the level of HDL cholesterol, (b) the level of LDL cholesterol, (c) the level of ALP, and (d) eating habits. LDL cholesterol: low-density lipoprotein cholesterol; HDL cholesterol: high-density lipoprotein cholesterol; ALP: alkaline phosphatase; Vegetarian: patients who eat only vegetarian food; Omnivorous: patients who eat any food well; Meat-based diet: patients who eat meat-based foods daily; (N): number of patients.

Figure 6

The percentage of uncultured Cyanobacterium spp. according to (a) the glucose and (b) LDL cholesterol levels; p = 0.0995. Glucose: fasting glucose level; LDL cholesterol; (N): number of patients.

Figure 7

Relationship between the abundance of phylum Cyanobacteria and that of the family Ruminococcaceae and the genus Lactobacillus, which are associated with liver disease, in the microbiome of patients with breast cancer. As the amount of the family Ruminococcaceae increases, the amount of Cyanobacteria decreases. As the amount of the genus Lactobacillus increases, the amount of Cyanobacteria also decreases. The bubble size and color correspond to the abundance of Cyanobacteria. There were some values lower than the 0.01 value that was set for the smallest bubble; however, these have been omitted from the graph to ensure clarity.

Figure 8

Comparison of the recurrence-free survival between the patients with breast cancer of group A (patients with an abundance of Cyanobacteria < 0.3%) and group B (patients with an abundance of Cyanobacteria ≥ 0.3%). The blue square box on the right shows the stage ratio of the patients of groups A and B when the patients were first recruited. Kaplan–Meier survival analysis was performed, and the log-rank p value was 0.0173.