Ma Jiayan, Gnanasekar Aditi, Lee Abby, Li Wei Tse, Haas Martin, Wang-Rodriguez Jessica, Chang Eric Y, Rajasekaran Mahadevan, Ongkeko Weg M
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, UC San Diego School of Medicine, San Diego, CA 92093, USA.
Research Service, VA San Diego Healthcare System, San Diego, CA 92093, USA.
Cancers (Basel). 2020 Sep 5;12(9):2524. doi: 10.3390/cancers12092524.
Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include , , , and , which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.
尽管每9名美国男性中就有1人会被诊断出患有前列腺癌（PC），但大多数被诊断出患有此病的男性不会因此死亡，因为大多数前列腺癌生长缓慢。然而，有一部分患者，原本生长缓慢的前列腺癌会发生转移，最终导致死亡。在这项研究中，我们分析了前列腺癌肿瘤内细菌的微生物组成，以确定微生物群对转移生长的影响。利用大规模RNA测序数据和相应的临床数据，我们将微生物的丰度与免疫途径和前列腺癌风险因素相关联，确定了对癌症侵袭性有显著抑制或促进作用的特定微生物。有趣的是，我们发现的大多数微生物似乎在前列腺癌中发挥抗肿瘤作用。由于这些抗肿瘤微生物在肿瘤样本中占比过高，我们认为微生物在肿瘤微环境中大量繁殖，胜过癌细胞，并通过招募免疫细胞直接减轻肿瘤生长。这些微生物包括 、 、 和 ，它们分别与 Gleason 评分、肿瘤-淋巴结-转移（TNM）分期、前列腺特异性抗原（PSA）水平和雄激素受体（AR）表达呈负相关。我们还确定了促进肿瘤生长的微生物，它们与基因组改变、免疫相关（IA）基因失调和前列腺癌干细胞（PCSC）基因呈正相关。
