Intratumoral Microbiota and Immune Microenvironment in Prostate Cancer

NCT07818421 | Not Yet Recruiting DMC

• 1 other identifier: KY2026-09-84
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer is a common malignancy in men, with rising incidence worldwide. Current clinical risk assessment tools-including PSA, Gleason score/ISUP grade, pathological stage, margin status, perineural invasion, and postoperative PSA kinetics-cannot fully explain the marked heterogeneity in disease progression, recurrence, and treatment response, highlighting the need for novel microenvironment-based biomarkers. Emerging evidence has identified intratumoral microbiota as a component of the tumor microenvironment in various solid tumors (e.g., breast, lung, ovarian, pancreatic, and melanoma), where microbial signals correlate with immune infiltration, inflammation, drug metabolism, and patient outcomes. However, the composition, spatial distribution, and immune-related roles of intratumoral microbiota in prostate cancer remain poorly characterized. Given that prostatic tissue resides at the urogenital junction and is continuously exposed to urine, prostatic fluid, and local inflammation, it is plausible that microbial components influence local immunity and tumor behavior. Importantly, intratumoral microbiota represent low-biomass samples, highly susceptible to contamination from reagents, environment, and laboratory procedures. Therefore, this study incorporates rigorous quality controls-including negative controls, process blanks, batch records, contaminant identification, spatial localization validation, and cross-platform verification-to ensure data reliability. Using residual tissue specimens, archived pathological slides, and comprehensive clinicopathological data from prostate cancer patients, we will employ 16S rRNA sequencing, metagenomic/metatranscriptomic sequencing, spatial transcriptomics, spatial proteomics, immunofluorescence, immunohistochemistry, and bioinformatic analyses to profile intratumoral microbiota. Our specific objectives are: (1) to compare microbial composition, abundance, and diversity among tumor, adjacent-normal, and benign tissues; (2) to validate spatial localization of candidate microbial signals via in situ hybridization, immunohistochemistry, and spatial omics; (3) to assess differences in immune cell infiltration, macrophage polarization, T-cell exhaustion markers, and inflammatory pathways between microbe-high and microbe-cold regions; (4) to explore associations between microbial features and Gleason score/ISUP grade, stage, perineural invasion, margin status, postoperative PSA changes, biochemical recurrence, and other clinical outcomes; and (5) to establish a standardized workflow for low-biomass intratumoral microbiome research in prostate cancer. This study aims to provide new insights into microenvironmental heterogeneity and to lay a foundation for identifying prognostic biomarkers and potential therapeutic targets.

Conditions

Prostate Cancer Adenocarcinoma

Keywords

Prostate cancer; Intratumoral microbiota; Tumor immune microenvironment; Spatial omics; Low-biomass microbiome

Outcome Measures

Primary Outcomes (1)

• Biochemical Progression-Free Survival (bPFS)

  Time from initiation of ADT plus ARPI therapy to biochemical progression or deathfrom any cause, whichever occurs first. Biochemical progression is defined as a PSA rise to 0.2ng/mL after having reached an undetectable level, confirmed by a second measurement at least 2weeks apart. Participants without an event will be censored at the date of last follow-up.

  From treatment initiation until biochemical progression or last follow-up, assessed every 3 months (+1 month) for up to 24 months.

Study Arms (1)

Patients with a pathological diagnosis of prostate cancer, or patients with benign prostatic disease

Diagnostic Test: Validate spatial localization of candidate microbial signals via 16S rRNA ISH, FISH, immunofluorescence, IHC, and spatial omics.

Interventions

Validate spatial localization of candidate microbial signals via 16S rRNA ISH, FISH, immunofluorescence, IHC, and spatial omics. DIAGNOSTIC_TEST

Compare microbe-high and microbe-cold areas for differences in immune cell infiltration, macrophage phenotype, T-cell exhaustion/suppression markers, inflammatory factors, and tumor-associated pathways.

Patients with a pathological diagnosis of prostate cancer, or patients with benign prostatic disease

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a pathological confirmation of prostate cancer, or patients who receive care for benign prostatic conditions and can be used as control subjects.

You may qualify if:

• （1）Age ≥18 years, male.（2）Patients with a pathological diagnosis of prostate cancer, or patients with benign prostatic diseases who undergo diagnostic workup or treatment and are eligible to serve as control samples.（3）Patients who undergo prostate biopsy, transurethral prostate surgery, radical prostatectomy, or other relevant diagnostic or therapeutic procedures at the First Affiliated Hospital of Anhui Medical University.（4）Have available residual tissue samples, formalin-fixed paraffin-embedded (FFPE) tissues, frozen tissues, pathological slides, or existing assay data that can be used for research purposes.（5）Have basic clinicopathological data available; postoperative PSA and follow-up information may be obtained when necessary.（6）For subjects from whom additional residual samples are prospectively collected, or for those who need to be actively contacted for supplementary data, the subject or their legal representative must consent to participate in the study and sign the informed consent form.

Sponsors & Collaborators

• Anhui Medical University: lead

Study Sites (1)

Universitythe First Affiliatedhospital of Anhuimedical

Hefei, Anhui, 230022, China

Location

Related Publications (13)

• Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations. Trends Microbiol. 2019 Feb;27(2):105-117. doi: 10.1016/j.tim.2018.11.003. Epub 2018 Nov 26.

  PMID: 30497919 RESULT

• de Goffau MC, Lager S, Salter SJ, Wagner J, Kronbichler A, Charnock-Jones DS, Peacock SJ, Smith GCS, Parkhill J. Recognizing the reagent microbiome. Nat Microbiol. 2018 Aug;3(8):851-853. doi: 10.1038/s41564-018-0202-y. No abstract available.

  PMID: 30046175 RESULT

• Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AW. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014 Nov 12;12:87. doi: 10.1186/s12915-014-0087-z.

  PMID: 25387460 RESULT

• Hurst R, Meader E, Gihawi A, Rallapalli G, Clark J, Kay GL, Webb M, Manley K, Curley H, Walker H, Kumar R, Schmidt K, Crossman L, Eeles RA, Wedge DC, Lynch AG, Massie CE; CRUK-ICGC Prostate Group; Yazbek-Hanna M, Rochester M, Mills RD, Mithen RF, Traka MH, Ball RY, O'Grady J, Brewer DS, Wain J, Cooper CS. Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups. Eur Urol Oncol. 2022 Aug;5(4):412-419. doi: 10.1016/j.euo.2022.03.006. Epub 2022 Apr 18.

  PMID: 35450835 RESULT

• Cavarretta I, Ferrarese R, Cazzaniga W, Saita D, Luciano R, Ceresola ER, Locatelli I, Visconti L, Lavorgna G, Briganti A, Nebuloni M, Doglioni C, Clementi M, Montorsi F, Canducci F, Salonia A. The Microbiome of the Prostate Tumor Microenvironment. Eur Urol. 2017 Oct;72(4):625-631. doi: 10.1016/j.eururo.2017.03.029. Epub 2017 Apr 20.

  PMID: 28434677 RESULT

• Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, Gavert N, Zwang Y, Cooper ZA, Shee K, Thaiss CA, Reuben A, Livny J, Avraham R, Frederick DT, Ligorio M, Chatman K, Johnston SE, Mosher CM, Brandis A, Fuks G, Gurbatri C, Gopalakrishnan V, Kim M, Hurd MW, Katz M, Fleming J, Maitra A, Smith DA, Skalak M, Bu J, Michaud M, Trauger SA, Barshack I, Golan T, Sandbank J, Flaherty KT, Mandinova A, Garrett WS, Thayer SP, Ferrone CR, Huttenhower C, Bhatia SN, Gevers D, Wargo JA, Golub TR, Straussman R. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017 Sep 15;357(6356):1156-1160. doi: 10.1126/science.aah5043.

  PMID: 28912244 RESULT

• Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E, Mishra A, Mohan N, Aykut B, Usyk M, Torres LE, Werba G, Zhang K, Guo Y, Li Q, Akkad N, Lall S, Wadowski B, Gutierrez J, Kochen Rossi JA, Herzog JW, Diskin B, Torres-Hernandez A, Leinwand J, Wang W, Taunk PS, Savadkar S, Janal M, Saxena A, Li X, Cohen D, Sartor RB, Saxena D, Miller G. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018 Apr;8(4):403-416. doi: 10.1158/2159-8290.CD-17-1134. Epub 2018 Mar 22.

  PMID: 29567829 RESULT

• Riquelme E, Zhang Y, Zhang L, Montiel M, Zoltan M, Dong W, Quesada P, Sahin I, Chandra V, San Lucas A, Scheet P, Xu H, Hanash SM, Feng L, Burks JK, Do KA, Peterson CB, Nejman D, Tzeng CD, Kim MP, Sears CL, Ajami N, Petrosino J, Wood LD, Maitra A, Straussman R, Katz M, White JR, Jenq R, Wargo J, McAllister F. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019 Aug 8;178(4):795-806.e12. doi: 10.1016/j.cell.2019.07.008.

  PMID: 31398337 RESULT

• Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA, Knight R. The microbiome and human cancer. Science. 2021 Mar 26;371(6536):eabc4552. doi: 10.1126/science.abc4552.

  PMID: 33766858 RESULT

• Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter-Maskowitz A, Weiser R, Mallel G, Gigi E, Meltser A, Douglas GM, Kamer I, Gopalakrishnan V, Dadosh T, Levin-Zaidman S, Avnet S, Atlan T, Cooper ZA, Arora R, Cogdill AP, Khan MAW, Ologun G, Bussi Y, Weinberger A, Lotan-Pompan M, Golani O, Perry G, Rokah M, Bahar-Shany K, Rozeman EA, Blank CU, Ronai A, Shaoul R, Amit A, Dorfman T, Kremer R, Cohen ZR, Harnof S, Siegal T, Yehuda-Shnaidman E, Gal-Yam EN, Shapira H, Baldini N, Langille MGI, Ben-Nun A, Kaufman B, Nissan A, Golan T, Dadiani M, Levanon K, Bar J, Yust-Katz S, Barshack I, Peeper DS, Raz DJ, Segal E, Wargo JA, Sandbank J, Shental N, Straussman R. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. 2020 May 29;368(6494):973-980. doi: 10.1126/science.aay9189.

  PMID: 32467386 RESULT

• Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.

  PMID: 39036382 RESULT

• Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.

  PMID: 38230766 RESULT

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Conduct analysis on residual tissue samples, archived tissue specimens, FFPE tissues, frozen tissues, pathological sections, and clinicopathological data acquired from prostate cancer patients throughout their diagnostic and therapeutic course.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

In Situ Hybridization, Fluorescence; Fluorescent Antibody Technique; Immunohistochemistry

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Histocytochemistry; Immunologic Techniques

Central Study Contacts

Sheng Tai, M.D.

CONTACT

86-18355159268; Taishengwk@163.com

Bowen Li, M.D.

CONTACT

86-18356721482; 2534582952@qq.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: the chief of the ward

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 14, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 14, 2026

Record last verified: 2026-09

Locations

CN (1)