Association of Mycoplasma hominis infection with prostate cancer

Abstract

The origin of chronic inflammation preceding the development of prostate cancer (PCa) remains unknown. We investigated possible involvement of mycoplasma infection in PCa by screening prostate biopsies from two groups of Russian men undergoing PCa diagnosis. M. hominis was detected by standard PCR in 15% of the 125 patients in the first group and by quantitative real-time PCR in 37.4% of the 123 men in the second group. In both groups, stratification of patients according to diagnosis showed that M. hominis was present at three times higher frequency in patients with PCa than in those with benign prostatic hyperplasia. No M. hominis was detected in the prostates of 27 men without detectable prostate disease. In addition, PCa-positive men had higher titers of antibodies against M. hominis and average PSA levels were higher in M. hominis-positive men. These data, together with previous observations linking mycoplasma infection with cell transformation, genomic instability and resistance to apoptosis, suggest that M. hominis infection may be involved in PCa development and may, therefore, be a potential PCa marker and/or target for improved prevention and treatment of this disease.

Figure 1. Detection of mycoplasma DNA in prostate tissue from Russian Patient Set 1 using standard PCR

A. Results of standard PCR assay for detection of an M. hominis DNA sequence (16S rRNA gene) and a control human DNA sequence (β-actin gene). 1 – no DNA template; 2 – “mock” DNA extraction; 3-7 – DNA from prostate biopsies of patients suspected of PCa; 8 – positive control (human DNA mixed with M. hominis DNA); 9 – DNA ladder. B. Frequency of detection of three Mycoplasma species in prostate biopsies (n=250, 2 from each of 125 patients) using standard PCR assays. The percentage of patients for which the PCR assay was positive in at least one biopsy sample is indicated. C. Frequency of detection of M. hominis DNA by standard PCR in prostate biopsies from patients in the indicated diagnosis categories and in prostate samples from negative control men (“lesion-free”).

Figure 2. Association of M. hominis infection with HGPIN and PCa

A. Frequency of detection of M. hominis DNA by qPCR in prostate biopsies from patients of Russian Patient Set 2 in the indicated diagnosis categories and in prostate samples from negative control men (“lesion-free”). B. Quantitation of M. hominis 16S rRNA gene copies by qPCR in M. hominis-positive prostate biopsies from patients in Russian Patient Set 2 with BPH (n=15 biopsies from 12 patients), HGPIN (n=28 biopsies from 17 patients) or PCa (n=25 biopsies from 17 patients). Each point indicates the concentration of M. hominis 16S rRNA DNA in a particular biopsy sample and the horizontal lines indicate the average value for each diagnosis group.

Figure 3. ELISA-based detection of anti-M. hominis IgG in the serum of patients suspected of PCa

ELISA was performed for 118 patients out of the 123 patients in Russian Patient Set 2 for which serum was available. The percentage of patients in BPH (n=52), HGPIN (n=29) and PCa (n=37) diagnosis categories that were positive by ELISA is shown.

Figure 4. The proportion of M. hominis-positive patients in which both prostate lobes were positive (R&L) or only the left (L) or right (R) lobe was positive

Data is from qPCR analysis of Russian Patient Set 2 and is shown for M. hominis-positive patients of all diagnosis groups (“total”, left column, n=46) or the HGPIN+PCa groups only (right column, n=34).

Figure 5. Serum PSA levels in patients suspected of PCa (Russian Patient Set 1) that were found to be M. hominis-negative (n=99) or –positive (n=26) by standard PCR

Each point represents an individual patient and the horizontal line indicates the mean within each group.