The microbiota and aging microenvironment in pancreatic cancer: Cell origin and fate

Chen, Zhou; Wang, Zhengfeng; Du, Yuchen; Shi, Huaqing; Zhou, Wence

doi:10.1016/j.bbcan.2022.188826

Cited by 5 publications

(11 citation statements)

References 194 publications

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“…The five-year survival rate of PAAD is only 5%. Due to difficult diagnosis and poor prognosis, research in PAAD in recent years has focused on finding new biomarkers to improve prognosis [ 17 ]. Cell death-related genes are potential biomarkers for the diagnosis and prognosis of PAAD.…”

Section: Discussionmentioning

confidence: 99%

A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Jiang

Hou

et al. 2023

BioMed Research International

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Background. Pancreatic cancer (PAAD) is a malignant tumor with a poor prognosis and lacks sensitive biomarkers for diagnosis and targeted therapy. Cuproptosis, a recently proposed form of cell death based on cellular copper ion concentration, plays a key role in cancer biology. This study is aimed at constructing a risk model for predicting the prognosis of PAAD patients based on cuproptosis-related genes. Methods. Pancreatic-related data from UCSC-TCGA and UCSC-GTEx databases were extracted for analysis, and TCGA-PAAD samples were randomly divided into the training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes coexpressed with 19 copper death genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of the Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Results. The Cox risk model has an eight prognostic cuproptosis-related gene signature. Kaplan-Meier survival curves demonstrated that the high-risk group had a shorter survival time. The ROC curve of the risk score was well created to predict one-, three-, and five-year survival rates, and AUC of the risk score was higher than other clinical characteristics. Cox regression analysis revealed that the risk score has an independent prognostic value for PAAD. GSEA reveals specific tumor pathways associated with the risk model (Myc targets v1, mTORC1 signaling, and E2F targets). Conclusions. We constructed a prognostic model containing eight cuproptosis-related genes (AKR1B10, KLHL29, PROM2, PIP5K1C, KIF18B, AMIGO2, MRPL3, and PI4KB) that can accurately predict the prognosis of PAAD patients. The results will provide new perspectives for individualized outcome prediction and new therapy development for PAAD patients.

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Section: Discussionmentioning

confidence: 99%

A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Jiang

Hou

et al. 2023

BioMed Research International

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“…Accumulating evidence suggests that microbiota play an important role in cancer by damaging cellular DNA, inducing transformation, activating and altering stromal cell components in the TME, and influencing cellular metabolism. 448,449 The microbiota characteristics under hypoxic conditions are currently not fully understood. Recent research has demonstrated that a combination of live bacteria and treatment modalities such as surgery, chemotherapy, and radiotherapy can produce good clinical outcomes.…”

Section: Biotherapymentioning

confidence: 99%

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Zhou

Han

et al. 2023

Sig Transduct Target Ther

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131

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Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.

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Section: Microbiota and Tumorigenesismentioning

confidence: 99%

“…SASPs are a group of paracrine signaling molecules secreted by senescent cells that include cytokines, chemokines, growth factors, and proteases 148 . In an autocrine or paracrine fashion, senescent cells promote the emergence of age‐related disorders, particularly cancers, while also aiding in tissue formation, suppressing tumors, tissue healing, and cell proliferation 144 . Evidence suggests that xenograft tumor growth can be accelerated by a dysregulated SASP that sustains inflammatory conditions in TME that promote cancer proliferation, migration, invasion, and EMT 144 .…”

Section: Microbiota and Tumorigenesismentioning

confidence: 99%

“…Microbiota can alter the malignant phenotype of tumors by inducing inflammation, modulating the antitumor immune system, altering TME, and influencing cellular metabolism, and is strongly linked to tumor patients' prognosis. 143 , 144 TLR activated by microbiota can cause derangements of multiple tumor suppressor proteins (e.g., p16, p21, p27, p53, pRb, PTEN, and MAP2K4), induce STAT3 activation, and enhance EMT and oncogene‐induced senescence. 145 Microbiota, on the other hand, can generate ROS by inducing a prolonged inflammatory response via changes of essential substance as lipids, nucleic acids, and preproteins that result in protein misfolding, membrane disintegration, and DNA fragmentation and accumulation over time, 143 which may dominate cellular senescence.…”

Section: Microbiota and Tumorigenesismentioning

confidence: 99%

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Microbiota in cancer: molecular mechanisms and therapeutic interventions

Chen,

Guan,

Wang

et al. 2023

MedComm

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The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota‐mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.

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The microbiota and aging microenvironment in pancreatic cancer: Cell origin and fate

Cited by 5 publications

References 194 publications

A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Microbiota in cancer: molecular mechanisms and therapeutic interventions

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