Trends and hotspots of prognostic factors for pancreatic ductal adenocarcinoma from 2013 to 2022.
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ABSTRACT:
SUBMITTER: Peng J
PROVIDER: S-EPMC11007332 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Trends and hotspots of prognostic factors for pancreatic ductal adenocarcinoma from 2013 to 2022.
Peng Jieyu J Lv Muhan M Peng Yan Y Tang Xiaowei X
Hepatobiliary surgery and nutrition 20240320 2
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Project description:BackgroundIncidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are on the rise. Sarcopenia and sarcopenic obesity have proven to be prognostic factors in different types of cancers. In the context of previous findings, we evaluated the impact of body composition in patients undergoing surgery in a national pancreatic center.MethodsPatient's body composition (n = 133) was analyzed on diagnostic CT scans and defined as follows: Skeletal muscle index ≤38.5 cm2/m2 (women), ≤52.4 cm2/m2 (men); obesity was classified as BMI ≥25kg/m2.ResultsSarcopenia showed a negative impact on overall survival (OS; 14 vs. 20 months, p = 0.016). Sarcopenic patients suffering from obesity showed poorer OS compared to non-sarcopenic obese patients (14 vs. 23 months, p = 0.007). Both sarcopenia and sarcopenic obesity were associated with sex (p<0.001 and p = 0.006; males vs. females 20% vs. 38% and 12% vs. 38%, respectively); sarcopenia was further associated with neoadjuvant treatment (p = 0.025), tumor grade (p = 0.023), weight loss (p = 0.02) and nutritional depletion (albumin, p = 0.011) as well as low BMI (<25 kg/m2, p = 0.038). Sarcopenic obese patients showed higher incidence of major postoperative complications (p<0.001). In addition, sarcopenia proved as an independent prognostic factor for OS (p = 0.031) in the multivariable Cox Regression model.ConclusionPatients with sarcopenia and sarcopenic obesity undergoing resection for PDAC have a significantly shorter overall survival and a higher complication rate. The assessment of body composition in these patients may provide a broader understanding of patients' individual condition and guide specific supportive strategies in patients at risk.
| S-EPMC6502449 | biostudies-literature
Project description:BackgroundMany real-world studies of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are restricted to single centers, limiting the generalizability of their insights. This study aimed to identify important population-based predictors for survival in patients diagnosed with mPDAC in a broader setting.MethodsData between 1 January 2017 and 31 December 2019 were extracted from the Flatiron Health EHR database. Treatment-specific predictive models were generated for patients treated with first-line gemcitabine+nab-paclitaxel (GNP), FOLFIRINOX, gemcitabine monotherapy (gem-mono), and second-line liposomal irinotecan-based regimens. The holdout method was used for cross-validation. Age at diagnosis, sex, BMI, smoking status, and ECOG performance score were included in all models with additional demographic, clinical characteristics, and hematological function assessed for inclusion.ResultsOf the 3625 patients, 43% received GNP, 26% received FOLFIRINOX, 7% received gem-mono, and 23% received other regimens; 40% (n = 1448) advanced to the second line. Among all first-line patients, the following were included in the final model: prior surgery, white blood cell (WBC) counts, serum albumin (SA), liver function tests (LFTs), serum bilirubin, serum carbohydrate antigen 19-9, and ascites. Models for patients receiving specific therapies differed from the overall model, GNP (ascites removed), FOLFIRINOX (stage at initial diagnosis added), and gem-mono (LFTs omitted). Alkaline phosphatase (ALP), SA, and WBC counts were important predictors of survival among patients treated with second-line liposomal irinotecan. Across all regimens, the strongest predictors of survival were ECOG score, SA, and ALP.ConclusionsIn this real-world study of patients with mPDAC, important population prognostic factors of survival were identified in a large cohort of patients receiving systemic treatment.
| S-EPMC8683530 | biostudies-literature
Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) leads to the majority of cancer-related deaths due to its morbidity with similar mortality. Lack of effective prognostic biomarkers are the main reason for belated post-operative intervention of recurrence which causes high mortality. Numerous systematic reviews and meta-analyses have explored the prognostic value of biomarkers in PDAC so far. In this article, we performed an umbrella review analyzing these studies to provide an overview of associations between prognostic biomarkers and PDAC survival outcome and synthesized these results to guide better clinical practice. Methods: Systematic reviews and meta-analyses investigating the associations between PDAC survival outcomes and prognostic biomarkers were acquired via the PubMed and Embase databases from inception till February 1, 2020. Associations supported by nominally statistically significant results were classified into strong, highly suggestive, suggestive, and weak based on several critical factors such as the statistical significance of summary estimates, the number of events, the estimate of the largest study included, interstudy heterogeneity, small-study effects, 95% predictive interval (PI), excess significance bias, and the results of credibility ceiling sensitivity analyses. Results: We included 41 meta-analyses containing 63 associations between PDAC survival outcomes and prognostic biomarkers. Although, none was supported by strong evidence among these associations, an association between C-reactive protein to albumin ratio (CAR) and PDAC overall survival (OS) and an association between neutrophil-lymphocyte ratio (NLR) and PDAC OS were supported by highly suggestive evidence. Otherwise, the association between lactate dehydrogenase (LDH) and PDAC OS was supported by suggestive evidence. The remaining 60 associations were supported by weak or not suggestive evidence. Conclusion: Associations between CAR or NLR and PDAC OS were supported by highly suggestive evidence. And the association between LDH and PDAC OS was supported by suggestive evidence. Although the methodological quality of the included systematic reviews and meta-analyses which were evaluated by AMSTAR2.0 is generally poor, the identification of the relatively robust prognostic biomarkers of PDAC may guide better post-operative intervention and follow-up to prolong patients' survival.
| S-EPMC7527774 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Here we show that shotgun and targeted protein sequencing can be used to identify potential prognostic biomarkers in formalin-fixed paraffin-embedded specimens from 9 patients with PDAC with "short" survival (<12 months) and 10 patients with "long" survival (>45 months) undergoing surgical resection. A total of 24 and 147 proteins were significantly upregulated [fold change ≥2 or ≤0.5 and P<0.05; or different detection frequencies (≥5 samples)] in patients with "short" survival (including GLUT1) and "long" survival (including C9orf64, FAM96A, CDH1 and CDH17), respectively. STRING analysis of these proteins indicated a tight protein-protein interaction network centered on TP53. Ingenuity pathway analysis linked proteins representing "activated stroma factors" and "basal tumor factors" to poor prognosis of PDAC. It also highlighted TCF1 and CTNNB1 as possible upstream regulators. Further parallel reaction monitoring verified that seven proteins were upregulated in patients with "short" survival (MMP9, CLIC3, MMP8, PRTN3, P4HA2, THBS1 and FN1), while 18 proteins were upregulated in patients with "long" survival, including EPCAM, LGALS4, VIL1, CLCA1 and TPPP3. Thus, we verified 25 protein biomarker candidates for PDAC prognosis at the tissue level. Furthermore, an activated stroma status and protein-protein interactions with TP53 might be linked to poor prognosis of PDAC.
| S-EPMC5839402 | biostudies-literature
Project description:BackgroundFrequent disease relapse and a lack of effective therapies result in a very poor outcome in pancreatic ductal adenocarcinoma (PDAC) patients. Thus, identification of prognostic biomarkers and possible therapeutic targets is essential. Besides their function in cell-cell adhesion, desmogleins may play a role in tumour progression and invasion that has not been investigated in PDAC to date. This study evaluated desmoglein expression as a biomarker in PDAC.MethodsUsing immunohistochemistry, we examined desmoglein 1 (DSG1), desmoglein 2 (DSG2) and desmoglein 3 (DSG3) expression in the tumour tissue of 165 resected PDAC cases. Expression levels were correlated to the patients' clinicopathological parameters and postoperative survival times. We confirmed these results in two independent gene expression data sets.ResultsA total of 36% of the tumours showed high DSG3 expression that correlated significantly with shorter patient survival (P=0.011) and poor tumour differentiation (P<0.001), whereas no such association was detected for DSG1 or DSG2. In RNA-Seq data and in microarray expression data, high DSG3 expression correlated significantly with poor survival (P=0.000356 and P=0.00499).ConclusionsWe identify DSG3 as a negative prognostic biomarker in resected PDAC, as high DSG3 expression is associated with poor overall survival and poor tumour-specific survival. These findings suggest DSG3 and its downstream signalling pathways as possible therapeutic targets in DSG3-expressing PDAC.
| S-EPMC4815888 | biostudies-literature
Project description:BackgroundOver the past decade, a plethora of studies have delved into the oral microbiome. Our objective was to evaluate the trends in oral microbiome research employing a quantitative approach.Materials and methodsWe extracted clinical studies on the oral microbiome published between 2013 and 2022 from the Web of Science database, yielding 3024 articles. The assembled literature was visually scrutinized using VOSviewer 1.6.18, Citespace 6.1.6, Pajek, Scimago Graphica, and other specialized software to assess authors, institutions, countries, journals, co-cited literature, keywords, genes, and diseases.ResultsOur analysis identified a total of 3024 articles. The volume and rate of annual publications steadily increased, with research interest in the oral microbiome progressively intensifying. The United States, China, and the UK contributed the highest number of publications. Growth rates of publications varied among countries over time. The Forsyth Institute emerged as the most collaborative institution, boasting the highest number of relevant papers (135) and securing the top rank, followed by Sichuan University and Harvard University. Paster Bruce J, Zhou Xuedong, and He Xuesong were pioneers in the field of oral microbiome research. This analysis demonstrates that the homeostatic balance of the oral microbiome, advanced microbial sequencing technology, connections with gut microbiota, and tumorigenesis, including oral cancer, have become emerging topics in the oral microbiome field.ConclusionsThis study delineated a comprehensive landscape of hotspots and frontiers in oral microbiome research, thus facilitating the identification of interdisciplinary advancements. We sincerely hope that our bibliometric analysis will enable researchers to leverage the oral microbiome to ultimately improve human oral health.
| S-EPMC10213461 | biostudies-literature
Project description:BackgroundBoth activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).MethodsThe densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated.ResultsPDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis.ConclusionCombined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection.
| S-EPMC8582170 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 1011 µ2 as cut-off value for all stages, patients seem to have longer overall survival (OS) (31 vs. 21 months, p = 0.495). For stage II, a TSA > 2 × 1011 µ2 was significantly associated with an R0 resection (p = 0.037). For stage III patients, a TSA > 1.9 × 1011 µ2 was significantly associated with a lower histological grade (p = 0.031), and a TSA > 2E + 11 µ2 was significantly associated with a preoperative AP ≥ 120 U/L (p = 0.009) and a lower preoperative AST (≤35 U/L) (p = 0.004). Patients with PDAC undergoing surgical resection with preoperative CA19.9 > 500 U/L and AST ≥ 100 U/L have an independent higher risk of recurrence. Tumor stroma could have a protective effect in these patients. A larger TSA is associated with an R0 resection in stage II patients and a lower histological grade in stage III patients, which may contribute to a longer OS.
| S-EPMC9955223 | biostudies-literature
Project description:Kallikreins play an important role in tumour microenvironment and as cancer biomarkers in different cancer entities. Previous studies suggested an upregulation of KLK10 and KLK6 in pancreatic ductal adenocarcinoma (PDAC). Therefore, we evaluated the clinicopathological role of these kallikreins and their value as biomarkers in PDAC.Differential expression was validated by DNA-microarrays and immunohistochemistry in normal and malignant pancreatic tissues. Sera concentrations of both kallikreins were evaluated using ELISA. In silico analysis of possible protein interactions and gene silencing of KLK10 in vitro using siRNAs gave further insights in the pathomechanisms.Gene expression analysis and immunohistochemistry demonstrated a strong expression for KLK10 and KLK6 in PDAC. Statistical analysis showed that co-expression of these kallikreins correlated with an R1-resection status (P=0.017) and worse outcome for overall survival (P=0.031). Multivariate analysis proofed that co-expression is an independent prognostic factor for survival (P=0.043). Importantly, KLK10 knockdown in AsPC-1 cells significantly reduced cell migration, whereas computational analysis suggested interaction of KLK6 with angiogenetic factors as an important mechanism.Co-expression of KLK10 and KLK6 plays an unfavourable role in PDAC. Our results suggest that this effect is likely mediated by an interaction with the factors of the extracellular matrix and enhancement of cancer cell motility.
| S-EPMC2579692 | biostudies-literature
Project description:Abstract Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long‐term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19–9 (CA19‐9) levels at diagnosis and preoperative chemotherapy with normalization of CA19‐9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long‐term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5‐year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long‐term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.
| S-EPMC10154895 | biostudies-literature