The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

Luan, Hong; He, Ye; Zhang, Tuo; Su, Yanna; Zhou, Liping

doi:10.1186/s12885-022-09577-2

Cited by 9 publications

(4 citation statements)

References 55 publications

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“…TIMER ( https://cistrome.shinyapps.io/timer/ ) is a computational tool that aids in comprehensively exploring the molecular characterization of tumor immune interactions across diverse tumors 11 . It calculates the abundances of six immune infiltrates (CD8 + T cells, CD4 + T cells, B cells, neutrophils, macrophages, and dendritic cells) based on RNA-Seq expression profiles data.…”

Section: Methodsmentioning

confidence: 99%

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel

Shah,

Rawal

2024

Sci Rep

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The lack of non-invasive methods for detection of early metastasis is a crucial reason for the poor prognosis of lung cancer (LC) liver metastasis (LM) patients. In this study, the goal was to identify circulating biomarkers based on a biomarker model for the early diagnosis and monitoring of patients with LCLM. An 8-gene panel identified in our previous study was validated in CTC, cfRNA and exosomes isolated from primary lung cancer with & without metastasis. Further multivariate analysis including PCA & ROC was performed to determine the sensitivity and specificity of the biomarker panel. Model validation cohort (n = 79) was used to verify the stability of the constructed predictive model. Further, clinic-pathological factors, survival analysis and immune infiltration correlations were also performed. In comparison to our previous tissue data, exosomes demonstrated a good discriminative value with an AUC of 0.7247, specificity (72.48%) and sensitivity (96.87%) for the 8-gene panel. Further individual gene patterns led us to a 5- gene panel that showed an AUC of 0.9488 (p = < 0.001) and 0.9924 (p = < 0.001) respectively for tissue and exosomes. Additionally, on validating the model in a larger cohort a risk score was obtained (RS > 0.2) for prediction of liver metastasis with an accuracy of 95%. Survival analysis and immune filtration markers suggested that four exosomal markers were independently associated with poor overall survival. We report a novel blood-based exosomal biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with LCLM.

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Section: Methodsmentioning

confidence: 99%

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel

Shah,

Rawal

2024

Sci Rep

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“…There are several factors that underlie a poor outcome in PDAC. The most severe is the high degree of metastatic dissemination to adjacent organs at disease presentation, with the most common site of metastasis being in liver [ 8 ]. Even in operable cases where the primary tumor has been completely resected, 75% of PDAC patients will succumb to a metastatic relapse in less than 5 years following their operation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Optimization of a mouse model of pancreatic cancer to simulate the human phenotypes of metastasis and cachexia

Spadafora,

Pryce,

Oles

et al. 2024

BMC Cancer

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Background Pancreatic ductal adenocarcinoma (PDAC) presents with a high mortality rate. Two important features of PDAC contribute to this poor outcome. The first is metastasis which occurs in ~ 80% of PDAC patients. The second is cachexia, which compromises treatment tolerance for patients and reduces their quality of life. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. Methods Here, we optimize an orthotopic mouse model of PDAC by altering several conditions, including the subcloning of parental murine PDAC cells, implantation site, number of transplanted cells, and age of recipient mice. We perform spatial profiling to compare primary and metastatic immune microenvironments and RNA sequencing to gain insight into the mechanisms of muscle wasting in PDAC-induced cachexia, comparing non-metastatic to metastatic conditions. Results These modifications extend the time course of the disease and concurrently increase the rate of metastasis to approximately 70%. Furthermore, reliable cachexia endpoints are achieved in both PDAC mice with and without metastases, which is reminiscent of patients. We also find that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. Conclusion Together, this model is likely to be advantageous in both advancing our understanding of the mechanism of PDAC cachexia, as well as in the evaluation of novel therapeutics.

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“…Although gemcitabine monotherapy or combination are first-line treatment for PDAC, many patients progress and beyond these regimens there are few treatment options available that provide significant and substantial response rates ( 4 ). Furthermore, PDAC metastasizes to the liver frequently and has been correlated with poor survival ( 5 ). This phase II clinical trial investigates a novel therapeutic strategy which utilizes seemingly low-impact drugs in PDAC, individually, that when combined improve efficacy.…”

mentioning

confidence: 99%

Editorial: Novel immunological characteristics and immunotherapeutic targets in pancreatic cancer

Khan,

Lou,

Sexton-Bonacci

2024

Front. Immunol.

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Editorial on the Research TopicNovel immunological characteristics and immunotherapeutic targets in pancreatic cancer Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and deadly disease with an overall 5-year survival rate of 13% (1). Current preclinical and clinical work is emerging to understand the interaction between the immune system, immunomodulatory processes and the tumor itself. Categorized as a 'cold-tumor', PDAC is seemingly non-responsive to immunotherapies, has a lack of T-cell infiltration, lack of tumor antigens and CD8+ T-cell exclusion (2). These factors make this disease difficult to treat compared to 'hot-tumors' which respond well to immune checkpoint (ICP) inhibitors and have better overall patient outcomes (3). The Research Topic, "Novel immunological characteristics and immunotherapeutic targets in pancreatic cancer" highlights emerging preclinical and clinical research that is aimed at modulating the tumor microenvironment (TME) and incorporating a strategy to rewire these 'cold-tumors' to allow for improved response rates to ICP inhibitors and address novel ways to target this disease.Hartupee et al. has reviewed the TME of PDAC, highlighting its role in therapeutic resistance. The article describes the molecular and cellular composition of the TME and discusses the desmoplastic environment created by stromal support cells and immunomodulatory cells, which leads to a dense, hypoxic microenvironment that promotes tumor growth and immune evasion. PDAC is considered a 'cold tumor' owing to its limited immunogenicity, which leads to weak immune responses and results in challenges for immunotherapy. Therefore, it's been suggested that targeting the TME alongside PDAC tumor cells can possibly convert an immunologically cold tumor into a 'hot tumor', overcoming immuno-therapeutic impediments. In this regard, CAR-T cell therapy, cancer vaccine therapy, use of bispecific T-cell engaging antibodies, antibody-drug conjugates, oncolytic virus and microbial therapies are some of the potential novel therapeutic strategies for effective PDAC treatment that have been discussed in detail by the authors. Understanding how to maximize these immune modulating strategies effectively by identifying patient populations or subgroups that may benefit from these Frontiers in Immunology frontiersin.org 01

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The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

Cited by 9 publications

References 55 publications

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel

Optimization of a mouse model of pancreatic cancer to simulate the human phenotypes of metastasis and cachexia

Editorial: Novel immunological characteristics and immunotherapeutic targets in pancreatic cancer

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