Tumor Budding Score Is a Strong and Independent Prognostic Factor in Patients With Pancreatic Ductal Adenocarcinoma: An Evaluation of Whole Slide Pathology Images of Large Sections

ObjectiveWe aimed to develop the tumor budding (TB) score and to explore the association between the TB score and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsIn this retrospective study, 130 consecutive patients with PDAC underwent surgical resection between July 2016 and March 2019. The location and counts of TB were assessed based on the digitalized whole slide hematoxylin and eosin images. The TB score was achieved using the Cox regression equation. The cutoff point for the TB score was determined by X-tile. Univariate and multivariate Cox regression models were used to analyze the association between the TB score and OS.ResultsThe TB score was 0.49 (range = 0–1.08), and the best cutoff for the TB score was 0.62. The duration of survival in individuals with a low TB score [median = 21.8 months, 95% confidence interval (CI) = 15.43–25.50] was significantly longer than that in those with a high TB score (median = 11.33 months, 95% CI = 9.8–14.22). Univariate analysis revealed that the TB score was significantly associated with OS [hazard ratio (HR) = 2.71, 95% CI = 1.48–4.96, p = 0.001]. Multivariate analysis revealed a strong and independent association between the TB score and OS (HR = 2.35, 95% CI = 1.27–4.33, p = 0.03). The high TB score group had a 2.14 times higher mortality than the low TB score group.ConclusionThe TB score is strongly and independently associated with the risk of OS in PDAC.

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Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.659168 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zengyu Feng ◽

Kexian Li ◽

Yulian Wu ◽

Chenghong Peng

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Extracellular Vesicles ◽

Immune Cell ◽

Cox Regression ◽

Univariate Analysis ◽

Functional Enrichment ◽

Ductal Adenocarcinoma ◽

Survival Curves ◽

Cox Regression Analysis ◽

Calibration Curves

Background: Accumulating evidence shows that the elevated expression of DCBLD2 (discoidin, CUB and LCCL domain-containing protein 2) is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Methods: Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan–Meier (K–M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC. Results: Univariate analysis, K–M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both DCBLD2 expression in tissue and extracellular vesicles had significant diagnostic value. Besides, DCBLD2 expression was correlated with infiltrating level of CD8+ T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 might be involved in cell motility, angiogenesis, and cancer-associated pathways. Conclusion: Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 might play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.

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Serum biomarker CD163 predicts overall survival in patients with pancreatic ductal adenocarcinoma

10.21203/rs.2.11901/v1 ◽

2019 ◽

Author(s):

Qinglin Fei ◽

Yu Pan ◽

Xingxing Yu ◽

Tianhong Teng ◽

Ronggui Lin ◽

...

Keyword(s):

Overall Survival ◽

Diagnostic Accuracy ◽

Pancreatic Ductal Adenocarcinoma ◽

Benign Tumor ◽

Univariate Analysis ◽

Ductal Adenocarcinoma ◽

Ca 125 ◽

Operating Characteristics ◽

Lymphocyte To Monocyte Ratio ◽

Scd163 Level

Abstract Background The serum soluble CD163 (sCD163) is elevated in patients with infection disease and several types of cancer. However, the prognostic value of serum sCD163 in pancreatic ductal adenocarcinoma (PDAC) has not yet been investigated. Methods Serum level of sCD163 was measured by using the peripheral blood of 54 patients with PDAC, 20 patients with benign tumor of pancreas, and 30 healthy volunteers (healthy controls). The association between serum sCD163 level and overall survival was analyzed. Receiver operating characteristics (ROCs) curves were generated, and areas under the curve (AUC) were compared to evaluate the diagnostic accuracy, including CA 19-9, CEA, CA 125, CA 153, serum sCD163 level and combination of sCD163 and CA19-9. Results Serum sCD163 level of patients with PDAC was significant higher than patients with benign tumor (p = 0.002) and health controls (p < 0.001). Using ROCs curves, we found that the AUC values of serum sCD163 were higher than those of CA 125 and CA 153, but lower than those of CA 19-9 and CEA. The combination of sCD163 and CA19-9 had higher diagnostic accuracy than CA19-9 or sCD163 alone. In addition, the prognosis of PDAC patients with sCD163 ≥ median was worse than sCD163 < median by using univariate analysis (p = 0.027). Further, multivariate analysis showed that higher level of serum sCD163 was still associated with poorer overall survival (p = 0.030). Serum sCD163 was not associated with tumoral CD163 expression, whereas negatively correlated with lymphocyte to monocyte ratio (r = -0.428, p = 0.001). Conclusion The serum sCD163 has the potential as a new promising parameter to predict the prognosis in PDAC patients.

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Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent

Journal of Personalized Medicine ◽

10.3390/jpm11020077 ◽

2021 ◽

Vol 11 (2) ◽

pp. 77

Author(s):

David Badovinac ◽

Katja Goričar ◽

Hana Zavrtanik ◽

Miha Petrič ◽

Teja Lavrin ◽

...

Keyword(s):

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Cox Regression ◽

Multivariable Analysis ◽

Extracellular Vesicle ◽

Ductal Adenocarcinoma ◽

Tumor Differentiation ◽

Treatment Optimization ◽

Curative Intent ◽

Optimized Treatment

Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann–Whitney test, Spearman’s rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, p = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560–0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (p = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (p = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.

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Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-143640/v1 ◽

2021 ◽

Author(s):

Zengyu Feng ◽

Kexian Li ◽

Minmin Shi ◽

Yeliu Feng ◽

Hao Chen ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Immune Cell ◽

Cox Regression ◽

Therapeutic Potential ◽

Univariate Analysis ◽

Functional Enrichment ◽

Ductal Adenocarcinoma ◽

Survival Curves ◽

Cox Regression Analysis ◽

Calibration Curves

Abstract Background: Accumulating evidence showed that the elevated expression of DCBLD2 is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated.Methods: Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan–Meier (K-M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC.Results: Univariate analysis, K-M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both tissue and extracellular vesicle-encapsulated DCBLD2 expression have significant diagnostic value. Besides, DCBLD2 expression is correlated with infiltrating level of CD8 + T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 may be involved in cell motility, angiogenesis, and cancer-associated pathways.Conclusions: Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 may play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.

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Efficacy of Chemopreventive Agents on Disease-free and Overall Survival in Patients With Pancreatic Ductal Adenocarcinoma: The CAOS Study

Case Medical Research ◽

10.31525/ct1-nct04245644 ◽

2020 ◽

Author(s):

Keyword(s):

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Chemopreventive Agents ◽

Disease Free

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Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

The American Surgeon ◽

10.1177/00031348211011129 ◽

2021 ◽

pp. 000313482110111

Author(s):

Weizheng Ren ◽

Dimitrios Xourafas ◽

Stanley W. Ashley ◽

Thomas E. Clancy

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Univariate Analysis ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Resection Margins ◽

Borderline Resectable ◽

Stepwise Selection ◽

R1 Resection ◽

Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

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A High C-Reactive Protein Level on Postoperative Day 7 is Associated with Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma after Resection

The American Surgeon ◽

10.1177/00031348211023406 ◽

2021 ◽

pp. 000313482110234

Author(s):

Masaji Tani ◽

Hiroya Iida ◽

Hiromitsu Maehira ◽

Haruki Mori ◽

Toru Miyake ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Median Overall Survival ◽

Cox Regression ◽

Ductal Adenocarcinoma ◽

C Reactive Protein ◽

Reactive Protein ◽

Retrospective View ◽

Node Metastases ◽

Common Malignancy

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy. While inflammation-related biomarkers influence patient survival after resection, it has not been known whether postoperative inflammations affect the survival of PDAC patients or not. Methods It was investigated whether the universal biomarkers on postoperative day (POD) 7 affect the survival of PDAC patients in the retrospective view, and univariate and multivariate analyses were performed via the Cox regression method. Results Overall, 108 consecutive patients underwent resection; 98 (90.7%) had T3 disease and 73 (67.6%) had lymph node metastases. Thirty-four patients (31.5%) experienced postoperative complications. Compared with preoperative values, the white blood cell count and C-reactive protein (CRP) level on POD 7 were significantly elevated ( P < .001 for both); conversely, the lymphocyte count was significantly reduced ( P < .001). Among 108 patients, 72 received adjuvant chemotherapy. The median overall survival was 21.0 months; the 5-year survival rate was 22.3%. On multivariate analysis, receiving adjuvant chemotherapy and low CRP levels on POD 7 (<7.6 mg/dL) were prognosticators of better survival. However, the CD classification was not a prognosticator of survival after resection. Conclusions Adjuvant chemotherapy and postoperative low CRP levels on POD 7 were prognosticators of better survival of PDAC patients after resection. Surgeons should be aware of managing postoperative infections because a high postoperative CRP level is related with unfavorable survival.

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Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma

Supportive Care in Cancer ◽

10.1007/s00520-020-05346-8 ◽

2020 ◽

Vol 28 (11) ◽

pp. 5271-5279 ◽

Cited By ~ 1

Author(s):

Shuichi Mitsunaga ◽

Eiji Kasamatsu ◽

Koji Machii

Keyword(s):

Overall Survival ◽

Weight Loss ◽

Pancreatic Ductal Adenocarcinoma ◽

Cancer Cachexia ◽

Ductal Adenocarcinoma ◽

Cancer Therapies ◽

First Line ◽

Timing Of Onset ◽

Line Chemotherapy

Abstract Purpose Cachexia influences the patient’s physical wellbeing and quality of life, and the patient’s ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. Results A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. Conclusion Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

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