The tumor immune microenvironment in long-term survival resected pancreatic cancer patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1054079 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27243564_1.fastq.gz | Fastqsanger.gz | |||
| SRR27243564_2.fastq.gz | Fastqsanger.gz | |||
| SRR27243565_1.fastq.gz | Fastqsanger.gz | |||
| SRR27243565_2.fastq.gz | Fastqsanger.gz | |||
| SRR27243566_1.fastq.gz | Fastqsanger.gz |
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Project description:This study aimed to elucidate immunological and microbial factors contributing to prolonged survival in pancreatic ductal adenocarcinoma (PDAC) patients, providing valuable guidance for treatment strategies that enhance efficacy. To accomplish this, we performed metatranscriptomics analyses and IF staining analyses to map the TIME in PDAC tumors from treatment-naïve short-term survivors (a cancer-specific survival of shorter than six months, STS) and long-term survivors (a cancer-specific survival over five years, LTS). In conclusion, our study unveiled a distinctive, yet intricate tumore immune microenvironment associated with prolonged survival in PDAC. This profile includes a decrease in pro-tumoral M2 and M0 macrophages, along with an increase in plasma B cells, all linked to a better prognosis in PDAC. Future research should be directed towards a more comprehensive understanding of the role of B cells in pancreatic cancer and the modulation of M2 macrophage polarization. Such insights will be invaluable in tailoring personalized therapeutic strategies to enhance patient outcomes.
2024-09-30 | GSE250445 | GEO
Project description:Purpose/Objective(s): To correlate gene expression and overall survival (OS) in patients with pancreatic adenocarcinoma who have undergone definitive surgery Materials/Methods: Patients were identified that were treated with definitive surgery without neoadjuvant and adjuvant therapy for pancreatic adenocarcinoma. The Beaumont BioBank consented patients then collected and stored tissue samples. Patients were grouped into short term (<10 months, n=13) and long term (>20 months, n=11) survivors. RNA was extracted from fresh frozen tissues, and global gene expression patterns in the short and longer-term survivors were compared. Pathway analysis of the significant genes was also performed. Results: The median age at the time of surgery was 64 years. The mean overall survival in each group was 7.5 months and 32.0 months. We identified 163 genes that were differentially expressed between patients who survived <10 months and >20 months from their definitive surgery. Many of the genes identified have known prognostic importance in oncology; however, less than half of these genes have been reported to be associated with survival in pancreatic adenocarcinoma. Pathway analysis identified expression targets of SP1, JUN, and EGF to be highly regulated based upon differences in overall survival. Conclusions: In pancreatic adenocarcinoma patients who have undergone definitive resection, we have identified multiple genes associated with inferior survival. Many of the genes reported in this study have not previously been linked to overall survival in this patient population.
2017-12-01 | GSE77435 | GEO
Project description:Background and aim: Only 10% of pancreatic ductal adenocarcinoma (PDAC) patients survive longer than five years. Factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients. Methods: The immune-related gene expression profiles of resected PDAC tumors of patients who survived and remained recurrence-free of disease for ≥36 months (long-term survivors, n=10) were compared to patients who had survived ≤6 months (short-term survivors, n=10) due to tumor recurrence. Validation was performed by the spatial protein expression profile of immune cells using the GeoMx™ Digital Spatial Profiler. An independent cohort of samples consisting of 12 long-term survivors and 10 short-term survivors, was used for additional validation. The independent validation was performed by combining qualitative immunohistochemistry and quantitative proteinexpression profiling. Results: B cells were found to be significantly increased in the TIME of longterm survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling in the discovery and the validation cohorts (p=0.002 and p=0.01, respectively). The higher number of infiltrated B cells was found mainly in the stromal compartments of PDAC samples and was exclusively found within tumor cells in long-term survivors. Conclusion: This is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found a higher number and a specific location of B cells in TIME of long-term survivors which emphasizes the importance of B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.
2022-12-14 | GSE220929 | GEO
Project description:Background: IL-33, a cytokine with pleiotropic functions, is elevated in serum of patients with hepatocellular carcinoma (HCC). This study investigated effects of local IL-33 expression in resected HCC on patient survival and on immunological and molecular tumor microenvironment. Methods: Tissue of resected HCCs was stained for H&E, masson trichrome, alpha smooth muscle actin, IL-33, CD8 and IL-13 and analysed by flow cytometry. Besides histomorphologic evaluation, the immunohistochemical stainings were analysed for the respective cell numbers separately for tumor area, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Further, gene expression of different HCC risk groups was compared using Micro Arrays. Results: In multivariable analysis, infiltration of HCCs by IL-33+ cells (P=0.032) and CD8+ cells (P=0.014) both independently were associated with prolonged patient survival. Flow cytometry demonstrated that cytotoxically active CD8+CD62L-KLRG1+CD107a+ effectory-memory cells are the main producers of IL-33 in these HCC patients. Using infiltration by IL-33+ and CD8+ cells as two separate factors, a HCC immune score (HCCIS) was designed and evaluated that stratified patient survival (P=0.0004). This HCCIS identified high and low risk patients who differ in gene expression profiles (P<0.001). Conclusion: Infiltration of HCCs by IL-33+ and CD8+ cells is independently associated with prolonged patient survival. We suggest that this is due to an induction of highly effective cytotoxically active CD8+CD62L-KLRG1+CD107a+ effector-memory cells producing IL-33. Based on these two independent factors we established a HCC immune score that provides risk stratification for HCC patients and can be used in the clinical setting. To investigate if HCCIS 0 high risk and HCCIS 2 low risk tumors exhibit a distinct molecular environment and gene expression pattern, RNA from fresh tumor tissue was isolated and analyzed by whole genome Microarray 4 patients with low risk tumors (HCCIS 2) were compared to 4 patients with high risk tumors (HCCIS 0).
2014-12-08 | E-GEOD-63850 | biostudies-arrayexpress
Project description:Background: IL-33, a cytokine with pleiotropic functions, is elevated in serum of patients with hepatocellular carcinoma (HCC). This study investigated effects of local IL-33 expression in resected HCC on patient survival and on immunological and molecular tumor microenvironment. Methods: Tissue of resected HCCs was stained for H&E, masson trichrome, alpha smooth muscle actin, IL-33, CD8 and IL-13 and analysed by flow cytometry. Besides histomorphologic evaluation, the immunohistochemical stainings were analysed for the respective cell numbers separately for tumor area, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Further, gene expression of different HCC risk groups was compared using Micro Arrays. Results: In multivariable analysis, infiltration of HCCs by IL-33+ cells (P=0.032) and CD8+ cells (P=0.014) both independently were associated with prolonged patient survival. Flow cytometry demonstrated that cytotoxically active CD8+CD62L-KLRG1+CD107a+ effectory-memory cells are the main producers of IL-33 in these HCC patients. Using infiltration by IL-33+ and CD8+ cells as two separate factors, a HCC immune score (HCCIS) was designed and evaluated that stratified patient survival (P=0.0004). This HCCIS identified high and low risk patients who differ in gene expression profiles (P<0.001). Conclusion: Infiltration of HCCs by IL-33+ and CD8+ cells is independently associated with prolonged patient survival. We suggest that this is due to an induction of highly effective cytotoxically active CD8+CD62L-KLRG1+CD107a+ effector-memory cells producing IL-33. Based on these two independent factors we established a HCC immune score that provides risk stratification for HCC patients and can be used in the clinical setting. To investigate if HCCIS 0 high risk and HCCIS 2 low risk tumors exhibit a distinct molecular environment and gene expression pattern, RNA from fresh tumor tissue was isolated and analyzed by whole genome Microarray
2014-12-08 | GSE63850 | GEO
Project description:Pancreatic cancer is the fourth leading cancer-related death in United States. The clinical relevance of genomic imbalances in pancreatic cancer is uncertain. We performed array-comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens from a Korean cohort. We observed recurrent copy number gains were observed in chromosome 1q, 11q, 18q11.1-11.2, and 20q13.13; and losses in chromosome 2p, 9p, 10q, 14q, 15q, 18q12.2-23, 19q, 20q11.1, 21p, and 22q. High copy number gains, with log2 ratio >2.0, were observed in 4 cytobands, encoding genes such as G protein-coupled receptor 48, c-myc and gamma-catenin. By comparing the aCGH results of long survivors and short survivors, determined according to the median survival, we observed that loss of cytoband 18q22.3, encoding 5 genes, was the only alteration with significantly different frequencies. The copy number of the CPGL (Carboxypeptidase of glutamate-like) gene in cytoband 18q22.3 was found to be significantly associated with overall survival in univariate analyses (p=0.019 by log-rank test). This was subsequently assessed in the Italian cohort: 41 out of the 61 specimens carried deletion of the CPGL gene. Patients with deletion of the CPGL gene also had shorter overall survival (p=0.003 by log-rank test). Multivariate analysis of the two cohorts combined showed that loss of 18q22.3 / deletion of the CPGL gene was an independent poor prognostic factor for overall survival after adjusting for other factors which were found to impact the outcome (hazard ratio 2.72, p=0.0007). overexpression of the CPGL or its alternating splicing isoform CPGL-B in a pancreatic cancer cell lines resulted in slower proliferation of cells, G1 cell cycle arrest, and reduced migration activity. In conclusion, through aCGH analysis, we identified loss of 18q22.3 / deletion of the CPGL gene as potentially being an independent poor prognostic factor in resected pancreatic cancer. We further identified the CPGL gene as a potential tumor suppressor for pancreatic cancer cell lines. Array-comparative genomic hybridization was performed in 44 resected pancreatic cancer specimen from a Korean cohort. Genomic alteration relating to prognosis of the Korean cohort was further validated in a Italian cohort containing 61 resected pancreatic cancer specimens.
2011-04-21 | E-GEOD-28732 | biostudies-arrayexpress
Project description:Interventions: Group 1: In this retrospective analysis, the following patient data are analyzed to compare the laser-assisted versus non-laser-assisted lung metastasisctomy with respect to long-term survival:
Age, sex, date of primary surgery, date of lung metastasectomy, localization of the metastasis, TNM staging, existence of extrapulmonal metastasis, neoadjuvant/adjuvant systemic treatments (chemotherapy, radiotherapy), date of recurrent surgery, surgical technique, surgical access, extent of resection, number of resected lung metastases, lung function data, number of dissected lymph nodes, resection margins, duration of hospitalisation, postoperative complications, date of recurrence, localization of recurrence, treatment at recurrence, date of death
Primary outcome(s): overall survival
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: treatment
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Project description:Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity
| PRJNA941286 | ENA
Project description:Recently neoadjuvant therapy (NAT) is being increasingly used in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, how NAT differentially impacts the tumor and the tumor microenvironment (TME) is still poorly defined. Therefore, we compared the spatial transcriptomics profiles in tumor and the TME of PDACs resected from patients with versus without NAT. We found that NAT can significantly upregulate multiple key complement genes (C3, C1S, C1R, C4B and C7) in TME but not in tumor, making the complement pathway the most significantly modified pathways by NAT. In addition, the NAT-treated patients s with higher TME complement show significantly higher expression of gene signatures for immunomodulatory and neurotropic fibroblast, mast cells, CD4+ T cells and monocytes, significantly lower expression of immune exhaustion gene signature, and improved overall survival. Our results suggested that NAT may have immunostimulatory effect for PDAC through upregulating TME complement signaling.
2024-06-05 | GSE240078 | GEO
Project description:ObjectiveTo investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD).MethodsThe tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized.ResultsHigh-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer.ConclusionsThe genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.
| S-EPMC8783870 | biostudies-literature