Despite various treatment attempts, the heterogenous group of soft tissue sarcomata (STS) with more than 100 subtypes still shows poor outcomes. Therefore, effective biomarkers for prognosis prediction and personalized treatment are of high importance. The Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase (PLOD) gene family, which is related to multiple cancer entities, consists of three members which encode important enzymes for the formation of connective tissue. The relation to STS, however, has not yet been explored. In this study, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the role of PLOD1–3 in STS. It was found that an overexpression of PLOD family members correlates with poor prognosis, which might be due to an increased infiltration of immune-related cells in the tumor microenvironment. In STS, the expression of PLOD genes could be a novel biomarker for prognosis and a personalized, more aggressive treatment in these patients.

Lower-grade glioma (LGG) is a group of tumors arising from the cells of the central nervous system. Although various therapy interventions are used, the prognosis remains different. Novel biomarkers are needed for the prognosis of disease and novel therapeutic strategies in LGG. The procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family contains three members and is related to multiple cancers, yet it was not investigated in LGG. Data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) cohorts were used to analyze the role of PLOD in LGG. As the PLOD family is involved in processes, such as tumor formation and cancer metastasis, we focused on its relationship to the tumor microenvironment (TME) in LGG. A high expression of the PLOD family relates to poor prognosis and high infiltration of immune cells within the TME. The expression level of the PLOD family might become a novel biomarker for prognosis and is a potential target for individual treatment decisions in LGG.

Pituitary tumor-transforming gene 1 (PTTG1) encodes a multifunctional protein that is involved in many cellular processes. However, the potential role of PTTG1 in tumor formation and its prognostic function in human pan-cancer is still unknown. The analysis of gene alteration, PTTG1 expression, prognostic function, and PTTG1-related immune analysis in 33 types of tumors was performed based on various databases such as The Cancer Genome Atlas database, the Genotype-Tissue Expression database, and the Human Protein Atlas database. Additionally, PTTG1-related gene enrichment analysis was performed to investigate the potential relationship and possible molecular mechanisms between PTTG1 and tumors. Overexpression of PTTG1 may lead to tumor formation and poor prognosis in various tumors. Consequently, PTTG1 acts as a potential oncogene in most tumors. Additionally, PTTG1 is related to immune infiltration, immune checkpoints, tumor mutational burden, and microsatellite instability. Thus, PTTG1 could be potential biomarker for both prognosis and outcomes of tumor treatment and it could also be a promising target in tumor therapy.

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

The overexpression of the enzymes involved in the degradation of procollagen lysine is correlated with various tumor entities. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) expression was found to be correlated to the progression and migration of cancer cells in gastric, lung and prostate cancer. Here, we analyzed the gene expression, protein expression, and the clinical parameters of survival across 33 cancers based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC), function annotation of the mammalian genome 5 (FANTOM5), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases. Genetic alteration, immune infiltration and relevant cellular pathways were analyzed in detail. PLOD3 expression negatively correlated with survival periods and the infiltration level of CD8+ T cells, but positively correlated to the infiltration of cancer associated fibroblasts in diverse cancers. Immunohistochemistry in colon carcinomas, glioblastomas, and soft tissue sarcomas further confirm PLOD 3 expression in human cancer tissue. Moreover, amplification and mutation accounted for the largest proportion in esophageal adenocarcinoma and uterine corpus endometrial carcinoma, respectively; the copy number alteration of PLOD3 appeared in all cancers from TCGA; and molecular mechanisms further proved the effect of PLOD3 on tumorigenesis. In particular, PLOD3 expression appears to have a tumor immunological effect, and is related to multiple immune cells. Furthermore, it is also associated with tumor mutation burden and microsatellite instability in various tumors. PLOD3 acts as an inducer of various cancers, and it could be a potential biomarker for prognosis and targeted treatment.

Le microbiote humain est défini par l’ensemble des microbes habitant un site corporel en particulier. Les différents microbiotes de l’Homme, notamment le microbiote intestinal qui est le plus étudié, peuvent moduler de nombreux mécanismes biologiques dont le métabolisme et la réponse immunitaire. Un débalancement du microbiote au niveau des espèces qui le composent, ou dysbiose, a été associé à plusieurs maladies inflammatoires comme le diabète, l’obésité, mais aussi divers types de cancer. De plus, il a été démontré que les bactéries pouvaient avoir un impact sur la réponse des patients aux thérapies contre le cancer. Le cancer du sein est le cancer le plus mortel chez la femme. Or, l’étiologie de la maladie reste incertaine. Récemment, il a été montré que des bactéries pouvaient infiltrer les tissus plus profonds comme le tissu mammaire, formant un microbiote local. Considérant l’impact que la dysbiose peut avoir sur la réponse immunitaire antitumorale et la réponse aux traitements, nous avons émis comme hypothèse qu’une présence bactérienne intratumorale similaire, en composition et en quantité, à celle du tissu normal non-cancéreux affecte la progression du cancer du sein ainsi que le devenir clinique des patientes. La présence du microbiote intratumoral du sein a donc été validée par la détection de plusieurs composants bactériens sur des coupes tumorales à l’aide de marquages moléculaires. Puis, nous avons évalué le rôle potentiel de ce microbiote en quantifiant et identifiant les espèces bactériennes présentes dans les tumeurs et les tissus normaux adjacents des patientes de notre cohorte du cancer du sein. Nos résultats montrent une abondance moins élevée de l’ADN bactérien dans les tumeurs du sein comparativement aux tissus normaux adjacents appariés, suggérant qu’une altération du microbiote mammaire est associée au cancer. De plus, les patientes ayant un signal bactérien très faible dans leur tumeur avaient un nombre de récidives plus élevé. Cette influence de la quantité apparente de bactéries sur le devenir clinique a été observée principalement chez les patientes ayant une tumeur avancée, soit un grade ou un stade élevé, et de sous-types moléculaires Luminal HER2+, HER2+ (non-luminal) et Luminal B. Aucune relation n’a été observée entre la composition bactérienne du microbiote intratumoral mammaire et la récidive. Nos travaux suggèrent une implication pronostique et thérapeutique de la charge bactérienne du microbiote associé aux tumeurs mammaires. / The human microbiota is defined by all the microbes inhabiting a specific body site. The different human microbiota, and in particular the intestinal microbiota which is the most studied, can modulate many biological mechanisms, including metabolism and the immune response. An imbalance in the bacterial species that compose the microbiota, or dysbiosis, has been associated with several inflammatory diseases such as diabetes, obesity, but also various types of cancer. Additionally, bacteria have been shown to impact the response of patients to cancer therapy. Breast cancer is the deadliest cancer in women. However, the etiology of the disease remains uncertain. Recently, it has been shown that bacteria can infiltrate deeper tissues like breast tissue, forming a local microbiota. Considering the impact that dysbiosis can have on the anti-tumor immune response and the response to treatments, we hypothesized that an intratumoral bacterial presence similar in composition and quantity to that of normal non-cancerous tissue affects the progression of breast cancer, as well as the clinical outcomes of patients. The presence of the intratumoral breast microbiota was therefore validated by the detection of several bacterial components on whole tumor sections using molecular staining. Then, we evaluated the potential role of this microbiota by quantifying and identifying the bacterial species present in tumors and adjacent normal tissues of patients in our breast cancer cohort. Our results show a lower abundance of bacterial DNA in breast tumors compared to adjacent paired normal tissues, suggesting that an alteration of the mammary microbiota is associated with breast cancer. In addition, patients with a very low bacterial signal in their tumor had a higher number of recurrences. This influence of the apparent quantity of bacteria on the clinical outcomes has been observed mainly in patients with an advanced tumor, either a high grade or a high stage, and of the Luminal HER2+, HER2+ (non-luminal) and Luminal B molecular subtype. No relationship has been observed between the bacterial composition of the breast intratumoral microbiota and the recurrence. Our work suggests a prognostic and therapeutic implication of the bacterial load of the microbiota associated with breast tumors.