Overall Survival Of Pancreatic Cancer Patients Research Articles

Resistance to gemcitabine is mediated by the circ_0036627/miR-145/S100A16 axis in pancreatic cancer.

The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of circular RNAs (circRNAs) in the tumorigenesis, progression and drug resistance of PC. However, the circRNAs underlying GEM resistance development of PC remains to be clarified. The current research aims to unveil the roles of circ_0036627 in dictating the aggressiveness and GEM sensitivity in PC. We reported the increased expression of circ_0036627 in PC tissues and PC cell lines. Elevated circ_0036627 expression level was correlated with advanced tumour grade and poor overall survival in PC patients. Functional assays and in vivo experiments demonstrated that circ_0036627 overexpression was required for the proliferation, migration invasion and GEM resistance in PC cells. circ_0036627 knockdown suppressed tumour development invivo. The molecular analysis further showed that circ_0036627 increased S100A16 expression by sponging microRNA-145 (miR-145), a tumour-suppressive miRNA that could significantly attenuate PC cell proliferation, migration, invasion and GEM resistance. Furthermore, our findings suggested that S100A16 acted as an oncogenic factor to promote aggressiveness and GEM resistance in PC cells. In conclusion, the current findings provide new mechanistic insights into PC aggressiveness and GEM resistance, suggesting the critical role of circ_0036627/miR-145/S100A16 axis in PC progression and drug resistance development and offering novel therapeutic targets for PC therapy.

Longitudinal changes in triceps skinfold thickness and serum albumin during chemotherapy in patients with pancreatic cancer: Gender-based prognostic insights—A prospective cohort study.

e16308 Background: Cachexia, characterized by distinct fat loss and poor nutritional status, is common in patients with pancreatic cancer. This study investigated the association between triceps skinfold thickness(TSF), indicative of body fat, and serum albumin levels, reflecting nutritional status, with overall survival(OS) in patients with pancreatic cancer. Methods: A prospective cohort of 353 patients with pancreatic cancer from April 2018 to June 2021 who received chemotherapy was queried. TSF(mm) and serum albumin(g/dL) were measured at baseline and every three weeks during follow-up. The optimal cutoffs for their six-month changes(six-month value minus initial value) were determined. We performed a landmark analysis of OS six months after the diagnosis of pancreatic cancer and assessed the factors influencing OS. Gender-specific survival analysis was conducted, culminating in the construction of nomograms for risk stratification. Results: Two hundred ninety-two patients survived over six months, with a median follow-up of 40.9 months. Changes in TSF, albumin, and protein levels over six months and initial albumin levels were independently associated with OS. Cancer stage, response to chemotherapy, and six-month serum CA 19-9 levels were also independent factors for OS. Gender-stratified analysis revealed gender-specific prognostic factors: TSF changes over six months£ 0 were associated with reduced OS (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.14–2.95) in men; initial albumin levels£ 3.5g/dl (HR, 5.73; 95% CI, 2.48–13.21) and albumin changes over six months£ -0.7g/dl (HR, 3.03; 95% CI, 1.51–6.07) were associated with reduced OS in women. Patients were categorized into low-, medium-, and high-risk groups for each gender based on nomogram scores, and increased risk levels were associated with elevated mortality risk. Conclusions: This was the first prospective cohort study to demonstrate that changes in TSF and albumin levels were associated with OS in pancreatic cancer patients undergoing chemotherapy in a gender-dependent manner.

Diagnostic and prognostic value of circulating exosomal glypican-1 in pancreatic cancer: a meta-analysis.

Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias. Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.

A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer.

Introduction: The involvement of endoplasmic reticulum (ER) stress in cancer biology is increasingly recognized, yet its role in pancreatic cancer (PC) remains unclear. This study aims to elucidate the impact of ER stress on prognosis and biological characteristics in PC patients. Methods: A bioinformatic analysis was conducted using RNA-seq data and clinicopathological information from PC patients in the TCGA and ICGC databases. The ER stress-associated gene sets were extracted from MSigDB. ER stress-associated genes closely linked with overall survival (OS) of PC patients were identified via log-rank test and univariate Cox analysis, and further narrowed by LASSO method. A risk signature associated with ER stress was formulated using multivariate Cox regression and assessed through Kaplan-Meier curves, receiver operating characteristic (ROC) analyses, and Harrell's concordance index. External validation was performed with the ICGC cohort. The single-sample gene-set enrichment analysis (ssGSEA) algorithm appraised the immune cell infiltration landscape. Results: Worse OS in PC patients with high-risk signature score was observed. Multivariate analysis underscored our ER stress-associated signature as a valuable and independent predictor of prognosis. Importantly, these results based on TCGA were further validated in ICGC dataset. In addition, our risk signature was closely associated with homeostasis, protein secretion, and immune regulation in PC patients. In particular, PC microenvironment in the high-risk cluster exhibited a more immunosuppressive status. At last, we established a nomogram model by incorporating the risk signature and clinicopathological parameters, which behaves better in predicting prognosis of PC patients. Discussion: This comprehensive molecular analysis presents a new predictive model for the prognosis of PC patients, highlighting ER stress as a potential therapeutic target. Besides, the findings indicate that ER stress can have effect modulating PC immune responses.

DUSP1 promotes pancreatic cancer cell proliferation and invasion by upregulating nephronectin expression

Abstract Objectives To explore the role of dual-specific phosphatase 1 (DUSP1) in the proliferation, migration and invasion of pancreatic cancer (PC). Methods TCGA and GTEx databases were used to investigate the relationship between DUSP1 expression and prognosis of PC patients. Expression efficiency of DUSP1 was validated by qPCR and western blotting. The proliferation of SW1990 and PANC-1 cells with DUSP1 overexpression or knockout was detected by EdU assays. The migratory and invasive abilities of cells were detected by wound healing and transwell assays. Results DUSP1 was highly expressed in PC and associated with poor prognosis of patients. Overexpression of DUSP1 promoted the proliferation, migration and invasion of PC cells by regulating nephronectin (NPNT), whereas knockout of DUSP1 exhibited the opposite effects. NPNT expression was positively correlated with DUSP1, and the overall survival of PC patients with high levels of NPNT was shorter. Conclusions DUSP1 promoted the proliferation, migration and invasion of PC cells by upregulating NPNT, suggesting DUSP1 may be a potential target for PC treatment.

LncRNA LZTS1-AS1 induces proliferation, metastasis and inhibits autophagy of pancreatic cancer cells through the miR-532 /TWIST1 signaling pathway

The 5 year survival rate after diagnosis of pancreatic cancer (PANC) is less than 5%, and it is one of the malignant tumors with the worst prognosis. Identification of novel oncogenes involved in the occurrence of pancreatic cancer is of great significance to improve the overall survival of PANC patients. Our previous study found that miR-532 is a key factor in PANC occurrence and development, and this study further explored its mechanism. We found that the expression of lncRNA LZTS1-AS1 was elevated in PANC tumor tissues and cells, and correlated with poor prognosis. In vitro experiments confirmed that LZTS1-AS1 could promote proliferation, oncogenicity, migration, and invasion of PANC cells, and inhibit apoptosis and autophagy. However, miR-532 had the completely opposite effect, and inhibition of miR-532 counteracted the effect of LZTS1-AS1 on PANC cells. Dual luciferase gene reporter assay and RNA immunoprecipitation assay confirmed the targeting relationship between LZTS1-AS1 and miR-532, and their expression levels were negatively correlated in PANC tissues. Overexpression of TWIST1 could counteract the effect of miR-532 in PANC cells, and the expression levels of both were negatively changed in PANC tissues and cells. Our results suggest that lncRNA LZTS1-AS1 acts as an oncogene to promote the metastasis of PANC and inhibit autophagy, and its mechanism may be to regulate TWIST1 through sponge miR-532. This study provides novel biomarkers and therapeutic targets for PANC.

Racial and socioeconomic disparities in time to chemotherapy and survival in patients with pancreatic cancer.

4100 Background: Pancreatic cancer is traditionally known to be an aggressive malignancy, requiring timely diagnosis and treatment, including chemotherapy and/or surgery. Prior studies have evaluated variances in overall survival (OS) based on race or income; however, research regarding time to treatment based on racial and socioeconomic disparities is underwhelmingly studied. Our project sought to evaluate the impact of race and income on time to chemotherapy and OS in pancreatic cancer patients receiving neoadjuvant or adjuvant chemotherapy. Methods: The National Cancer Database (NCDB) from 2004-2020 was reviewed for patients with a diagnosis of pancreatic cancer, including all types and stages. Exclusion criteria included: no documented income level, time to first treatment surgery, or time to chemotherapy. Our patient population was then separated into two cohorts: neoadjuvant and adjuvant. Income level was stratified into the following: < $30,000, $30,000-34,999, $35,000-$45,999, and > $46,000. Race was also noted. We utilized a logistic regression to identify factors associated with longer time to chemotherapy (using median time to chemotherapy as a benchmark for early or later initiation of chemotherapy). A Cox proportional hazards model was used to identify factors associated with worse survival. A p-value < 0.05 was deemed significant. Results: Our final sample size included 64,640 patients. 6,887 (10.6%) of patients had an income less than $30,000. 55,340 (85.6%) of patients were Caucasian, 6,379 (9.9%) patients were African American, and 172 (0.002%) were American Indian. 18,679 (28.9%) received neoadjuvant chemotherapy, and 45,961 (71.1%) received adjuvant chemotherapy. Median time to chemotherapy was 27 [0-2048] days and 71 [0-1895] days in the neoadjuvant and adjuvant cohorts, respectively. Within both cohorts, income > $46,000 was noted to have significantly earlier time to chemotherapy compared to lower income levels. Those privately insured had significantly earlier time to chemotherapy compared to uninsured. The African American population was associated with a later time to first chemotherapy in comparison to Caucasians in both subgroups. A significantly less OS in the African American population was appreciated in the neoadjuvant cohort (HR 0.92, p-value 0.02), but not the adjuvant cohort. Conclusions: Our retrospective analysis emphasizes that minorities and/or those with a poor socioeconomic status have significant delay in time to chemotherapy in the neoadjuvant and adjuvant setting. Within the African American neoadjuvant cohort, a significantly worse OS was highlighted. This study emphasizes racial and socioeconomic disparities in our healthcare system. Limitations of our study include its retrospective nature and no information regarding the type of surgery the patients received, which could further account for differences in time to chemotherapy.

Value of thyroid cancer history in the prognosis of pancreatic cancer: a SEER population-based study

Thyroid cancer patients have a good prognosis, and their long survival increases the likelihood of developing a second primary tumor. Meanwhile, pancreatic cancer (PC) has a poor prognosis and therapeutic efficacy. However, the association between prior thyroid cancer and the subsequent PC prognosis is unknown. Herein, we selected pathologically diagnosed PC patients older than 17 between 2010 and 2015 from the SEER database. We used propensity score matching (PSM) to reduce confounding factors between groups and matched each PC patient with a history of thyroid cancer with 10 PC patients without a history of thyroid cancer. Finally, we selected 103 PC patients with prior thyroid cancer and 1030 PC patients without prior thyroid cancer. Then, we analyzed the factors influencing the overall survival (OS) and the cancer-specific survival (CSS) of PC patients. The median overall survival of PC patients with and without a history of thyroid cancer was 12 and 9 months, respectively. The history of thyroid cancer in PC patients reduced the PC-specific mortality (p < 0.05). Prior thyroid cancer might be a favorable prognostic factor for PC-specific mortality in PC patients.

Prognostic factors for survival in pancreatic cancer patients received radiotherapy: a single-center experience

Aim: To investigate survival outcomes and factors affecting the prognosis of patients with pancreatic cancer (PC) who received radiotherapy (RT).Material and Method: A total of 73 patients with PC who received RT between 2013 and 2021 were included in the study. Clinical, demographic, and histopathological features of the patients, and the goal of RT (adjuvant, definitive, neoadjuvant, or palliative) were recorded. Results: Median age of the patients was 62 (37-78). Male to female ratio was 1.6. In patients treated with adjuvant (n=52), definitive (n=13), and palliative (n=7) RT, median overall survival (OS) was 25.7 (11.6-39.7), 16 (7-67), and 9 (5-52) months, respectively. Survival time of 1 patient who received neoadjuvant RT was 26.6 months. Lymph node ratio (LNR) was significantly associated with OS. Patients with LNR ≤0.4 had better survival compared to those with LNR &amp;gt;0.4 (p=0.003). Furthermore, patients with LNR ≤0.4 and received adjuvant RT survived longer than the rest of the patients (12.1 vs. 7.7 months, p=0.001). Larger tumors (p=0.04) and LNR (p=0.003) were associated with poorer survival in univariate analysis, however, in the multivariate analysis, OS was found significantly affected only by LNR (p=0.01). Other factors were not found associated with survival. Conclusion: LNR had a strong correlation with OS in PC patients treated with radiation. Smaller LNR was associated with better survival in patients who received RT in the adjuvant setting.

Prognostic significance ofPD-L1 expression in pancreatic cancer: evidence from anupdated meta-analysis.

Recent studies revealed that programmed cell death ligand 1 (PD-L1) expression was associated with unfavorable prognosis in various solid tumors, but its clinical relevance for pancreatic cancer has not yet been well established. This meta-analysis summarizes thepotential prognostic value ofPD-L1 in pancreatic cancer. Aquantitative meta-analysis was performed by asystematic search ofdatabases including PubMed, EMBASE, Web ofScience, Cochrane library, Scopus and Ovid for eligible studies on theprognostic significance ofPD-L1 in pancreatic cancer patients. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated to evaluate thestrength ofthelink between PD-L1 expression and clinical prognosis ofpatients. Seventeen eligible studies with 2669 patients were included in our study. Asignificant association was observed between PD-L1 abundance and poor overall survival (OS) ofpatients with pancreatic cancers, with apooled hazard ratio (HR) of1.902, 95% CI: 1.657-2.184. Sensitivity analysis confirmed thereliability ofour results. Subgroup analysis shows that differences in regions and detection methods ofPD-L1 did not change theoverall predictive value ofPD-L1 for poor prognosis in pancreatic cancer patients. This meta-analysis indicated that theexpression ofPD-L1 is associated with aworse OS in pancreatic cancer patients. Additionally, PD-L1 may act as a potential parameter for predicting poor prognosis and thus providing apromising target for anticancer therapy in pancreatic cancer.

The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

A 70‑RNA model based on SVR and RFE for predicting the pancreatic cancer clinical prognosis.

Researches on the prognosis of pancreatic cancer is of great significance to improve the patient treatment effect and survival. Current researches mainly focus on the prediction of the survival status and the determination of prognostic markers. Each patient has its own characteristics, there is no report about the prediction of survival time. However, accurate prediction of survival time is critical for personalized medicine. In this paper, a hybrid algorithm of Support Vector Regression (SVR) and Recursive Feature Elimination (RFE) was used to construct a quantitative prediction model of Overall Survival (OS) for pancreatic cancer patients, 70 RNAs related to OS were determined, including 33 mRNAs, 28 lncRNAs, and 9 miRNAs. The results of 10-fold cross-validation (R2 is 0.9693) and the generalization ability (R2 is 0.9666) showed that the model has reliable predictive performance and these 70 RNAs are important factors influencing the OS of pancreatic cancer patients. To further study the relationship between RNA-RNA interaction and the survival, competitive endogenous RNA (ceRNA) regulation network was constructed. Degree centrality, betweenness centrality and closeness centrality of nodes in the ceRNA network showed that hsa-mir-570, hsa-mir-944, hsa-mir-6506, hsa-mir-3136, MMP16, PLGLB2, HPGD, FUT1, MFSD2A, SULT1E1, SLC13A5, ZNF488, F2RL2, TNFRSF8, TNFSF11, FHDC1, ISLR2 and THSD7B are hub nodes, which are key RNAs closely determining the OS of pancreatic cancer patients.

Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer

BackgroundAlthough gemcitabine has been considered as the first-line drug for advanced pancreatic cancer (PC), development of resistance to gemcitabine severely limits the effectiveness of this chemotherapy, and the underlying mechanism of gemcitabine resistance remains unclear. Various factors, such as ATP binding cassette (ABC) transporters, microRNAs and their downstream signaling pathways are included in chemoresistance to gemcitabine. This study investigated the potential mechanisms of microRNAs and ABC transporters related signaling pathways for PC resistance to gemcitabine both in vivo and in vitro.MethodsImmunohistochemistry and Western blotting were applied to detect the expression of ABC transporters. Molecular docking analysis was performed to explore whether gemcitabine interacted with ABC transporters. Gain-of-function and loss-of-function analyses were performed to investigate the functions of hsa-miR-3178 in vitro and in vivo. Bioinformatics analysis, Western blotting and dual-luciferase reporter assay were used to confirm the downstream regulatory mechanisms of hsa-miR-3178.ResultsWe found that P-gp, BCRP and MRP1 were highly expressed in gemcitabine-resistant PC tissues and cells. Molecular docking analysis revealed that gemcitabine can bind to the ABC transporters. Hsa-miR-3178 was upregulated in gemcitabine resistance PANC-1 cells as compared to its parental PANC-1 cells. Moreover, we found that hsa-miR-3178 promoted gemcitabine resistance in PC cells. These results were also verified by animal experiments. RhoB was down-regulated in gemcitabine-resistant PC cells and it was a downstream target of hsa-miR-3178. Kaplan–Meier survival curve showed that lower RhoB expression was significantly associated with poor overall survival in PC patients. Rescue assays demonstrated that RhoB could reverse hsa-miR-3178-mediated gemcitabine resistance. Interestingly, hsa-miR-3178 promoted gemcitabine resistance in PC by activating the PI3K/Akt pathway-mediated upregulation of ABC transporters.ConclusionsOur results indicate that hsa-miR-3178 promotes gemcitabine resistance via RhoB/PI3K/Akt signaling pathway-mediated upregulation of ABC transporters. These findings suggest that hsa-miR-3178 could be a novel therapeutic target for overcoming gemcitabine resistance in PC.

TMEM43 promotes pancreatic cancer progression by stabilizing PRPF3 and regulating RAP2B/ERK axis

BackgroundTransmembrane protein 43 (TMEM43), a member of the transmembrane protein subfamily, plays a critical role in the initiation and development of cancers. However, little is known concerning the biological function and molecular mechanisms of TMEM43 in pancreatic cancer.MethodsIn this study, TMEM43 expression levels were analyzed in pancreatic cancer samples compared with control samples. The relationship of TMEM43 expression and disease-free survival (DFS) and overall survival (OS) were assessed in pancreatic cancer patients. In vitro and in vivo assays were performed to explore the function and role of TMEM43 in pancreatic cancer. Coimmunoprecipitation (co-IP) followed by protein mass spectrometry was applied to analyze the molecular mechanisms of TMEM43 in pancreatic cancer.ResultsWe demonstrated that TMEM43 expression level is elevated in pancreatic cancer samples compared with control group, and is correlated with poor DFS and OS in pancreatic cancer patients. Knockdown of TMEM43 inhibited pancreatic cancer progression in vitro, decreased the percentage of S phase, and inhibited the tumorigenicity of pancreatic cancer in vivo. Moreover, we demonstrated that TMEM43 promoted pancreatic cancer progression by stabilizing PRPF3 and regulating the RAP2B/ERK axis.ConclusionsThe present study suggests that TMEM43 contributes to pancreatic cancer progression through the PRPF3/RAP2B/ERK axis, and might be a novel therapeutic target for pancreatic cancer.

Identification and Validation of Constructing the Prognostic Model With Four DNA Methylation-Driven Genes in Pancreatic Cancer

Background: Pancreatic cancer (PC) is a highly aggressive gastrointestinal tumor and has a poor prognosis. Evaluating the prognosis validly is urgent for PC patients. In this study, we utilized the RNA-sequencing (RNA-seq) profiles and DNA methylation expression data comprehensively to develop and validate a prognostic signature in patients with PC. Methods: The integrated analysis of RNA-seq, DNA methylation expression profiles, and relevant clinical information was performed to select four DNA methylation-driven genes. Then, a prognostic signature was established by the univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses in The Cancer Genome Atlas (TCGA) dataset. GSE62452 cohort was utilized for external validation. Finally, a nomogram model was set up and evaluated by calibration curves. Results: Nine DNA methylation-driven genes that were related to overall survival (OS) were identified. After multivariate Cox and LASSO regression analyses, four of these genes (RIC3, MBOAT2, SEZ6L, and OAS2) were selected to establish the predictive signature. The PC patients were stratified into two groups according to the median risk score, of which the low-risk group displayed a prominently favorable OS compared with the high-risk group, whether in the training (p < 0.001) or validation (p < 0.01) cohort. Then, the univariate and multivariate Cox regression analyses showed that age, grade, risk score, and the number of positive lymph nodes were significantly associated with OS in PC patients. Therefore, we used these clinical variables to construct a nomogram; and its performance in predicting the 1-, 2-, and 3-year OS of patients with PC was assessed via calibration curves. Conclusion: A prognostic risk score signature was built with the four alternative DNA methylation-driven genes. Furthermore, in combination with the risk score, age, grade, and the number of positive lymph nodes, a nomogram was established for conveniently predicting the individualized prognosis of PC patients.

A TP53-associated immune prognostic signature for the prediction of the overall survival and therapeutic responses in pancreatic cancer.

Pancreatic cancer (PC) is a highly fatal disease correlated with an inferior prognosis. The tumor protein p53 (TP53) is one of the frequent mutant genes in PC and has been implicated in prognosis. We collected somatic mutation data, RNA sequencing data, and clinical information of PC samples in the Cancer Genome Atlas (TCGA) database. TP53 mutation was an independent prognostic predictor of PC patients. According to TP53 status, Gene set enrichment analysis (GSEA) suggested that TP53 mutations were related to the immunophenotype of pancreatic cancer. We identified 102 differentially expressed immune genes (DEIGs) based on TP53 mutation status and developed a TP53-associated immune prognostic model (TIPM), including Epiregulin (EREG) and Prolactin receptor (PRLR). TIPM identified the high-risk group with poor outcomes and more significant response potential to cisplatin, gemcitabine, and paclitaxel therapies. And we verified the TIPM in the International Cancer Genome Consortium (ICGC) cohort (PACA-AU) and Gene Expression Omnibus (GEO) cohort (GSE78229 and GSE28735). Finally, we developed a nomogram that reliably predicts overall survival in PC patients on the bias of TIPM and other clinicopathological factors. Our study indicates that the TIPM derived from TP53 mutation patterns might be an underlying prognostic therapeutic target. But more comprehensive researches with a large sample size is necessary to confirm the potential.

Controlling nutritional status (CONUT) score-based nomogram to predict overall survival of patients with pancreatic cancer undergoing radical surgery

/Objective: As a new immune-nutritional marker, the controlled nutritional status (CONUT) score has been reported to predict the prognosis of cancer patients. We aimed to elucidate the prognostic value of preoperative CONUT score in pancreatic cancer patients undergoing radical surgery, and to construct a nomogram based on CONUT score to predict individual survival. Preoperative CONUT scores were calculated prospectively in 382 patients with pancreatic cancer who underwent radical surgery. Evaluated the relationship between CONUT score and pancreatic cancer prognosis. Cox proportional hazard models were used to determine predictors of survival and a new nomogram was established to predict pancreatic cancer overall survival (OS). The area under curve of CONUT score was higher than other immune-nutritional indexes. The OS of the high-CONUT group were significantly lower than that of low-CONUT group. Multivariate analysis showed that CONUT score, gender, AJCC stage, complications and reoperation were independent prognostic factors for OS. Nomogram based on these variables has better discriminant ability in predicting survival compared with other traditional staging systems. Preoperative CONUT score is an effective independent predictor of OS in pancreatic cancer patients undergoing radical surgery. This new CONUT based nomogram provides accurate, individualized survival prediction for pancreatic cancer.

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT.

Simple SummaryFDG uptake of bone marrow (BM) is known to reflect the degree of host inflammatory response to cancer cells and showed significant association with survival in diverse kinds of cancers. The aim of this retrospective study was to evaluate the prognostic significance of FDG uptake of BM and to investigate whether integrating FDG uptake of BM and radiomic features of primary tumors could improve the prediction of overall survival (OS) in patients with pancreatic cancer. In multivariable survival analysis, along with total lesion glycolysis (TLG) and first-order entropy of primary tumor lesions, FDG uptake of BM was an independent predictor of OS. We designed a PET/CT scoring system based on the cumulative scores of tumor factors (TLG and first-order entropy) and host factors (FDG uptake of BM). This scoring system was able to stratify the patients with three distinct prognostic groups independent of clinical stage and treatment modality.The purpose of this study was to evaluate the prognostic significance of FDG uptake of bone marrow (BM SUV) and to investigate its role combined with radiomic features of primary tumors in improving the prediction of overall survival (OS) in patients with pancreatic cancer. We retrospectively enrolled 65 pancreatic cancer patients with staging FDG PET/CT. BM SUV and conventional imaging parameters of primary tumors including total lesion glycolysis (TLG) were measured. First-order and higher-order textural features of primary cancer were extracted using PET textural analysis. Associations of PET/CT parameters of bone marrow (BM) and primary cancer with OS were assessed. BM SUV as well as TLG and first-order entropy of pancreatic cancer were significant independent predictors of OS in multivariable analysis. A PET/CT scoring system based on the cumulative scores of these three independent predictors enabled patient stratification into three distinct prognostic groups. The scoring system yielded a good prognostic stratification based on subgroup analysis irrespective of tumor stage and treatment modality. BM SUV was an independent predictor of OS in pancreatic cancer patients. The PET/CT scoring system that integrated PET/CT parameters of primary tumors and BM can provide prognostic information in pancreatic cancer independent of tumor stage and treatment.

Preoperative Alkaline Phosphatase-to-Cholesterol Ratio as a Predictor of Overall Survival in Pancreatic Ductal Adenocarcinoma Patients Undergoing Radical Pancreaticoduodenectomy.

BackgroundThe value of alkaline phosphatase and cholesterol for predicting overall survival (OS) in cancer patients has been previously studied. However, the predictive value of these variables in patients with pancreatic ductal adenocarcinoma (PDAC) was limited. Hence, we conducted this study to investigate the prognostic value of the alkaline phosphatase-to-cholesterol ratio (ACR) in patients undergoing radical pancreaticoduodenectomy (PD) for PDAC.Material/MethodsA total of 102 PDAC patients undergoing radical PD at the Cancer Hospital Chinese Academy of Medical Sciences were retrospectively enrolled based on medical records from June 2009 to June 2019. R programming language was used for the optimal cutoff value of biological markers such as preoperative ACR. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis.ResultsThe optimal cutoff value of preoperative ACR was 32.988. Patients with higher preoperative ACR values had worse OS (P<0.001). Higher preoperative ACR was significantly correlated with the degree of tumor differentiation (P<0.018); levels of alanine aminotransferase (P<0.001), aspartate aminotransferase (P<0.001), total bilirubin (P<0.001), and carbohydrate antigen 19-9 (P=0.016); and clinical symptoms (P=0.001). Multivariate analysis showed that tumor differentiation (P<0.001), ACR value (hazard ratio [HR]: 2.225, 95% confidence interval [CI]: 1.33–3.724, P=0.002), and sex (HR, 1.725, 95% CI: 1.1–2.704, P=0.018) were independent factors associated with the prognosis of PDAC patients undergoing radical PD.ConclusionsThe preoperative ACR was correlated with OS in pancreatic cancer patients undergoing radical pancreaticoduodenectomy. Elevated ACR was correlated with poor OS.

Preoperative sarcopenia is associated with poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.

To analyze the effect of preoperative body composition on survival in patients with pancreatic cancer following pancreaticoduodenectomy (PD). Between October 2005 and August 2018, 116 patients (68 men, 48 women, mean age 66.2 ± 11.9 years) diagnosed with pancreatic adenocarcinoma following PD were retrospectively enrolled. The preoperative CT on vertebral level L3 was assessed for total abdominal muscle area (TAMA), visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and mean skeletal muscle attenuation (SMD). The clinical data and pathological findings of tumors were collected. The impact of these factors on disease-free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier method and by univariable and multivariable Cox proportional hazards models. The 3-year DFS and OS rates were 8% and 25%, respectively. Of 116 patients, 20 (17.2%), 3 (2.6%), and 46 (39.7%) patients were classified as having sarcopenia, sarcopenic obesity, and myosteatosis, respectively. The VAT-TAMA ratio (1.2 ± 0.7 vs 0.9 ± 0.5, p = 0.01) and the visceral to subcutaneous adipose tissue area ratio (1.3 ± 0.7 vs 0.9 ± 0.5, p = 0.04) were higher in sarcopenic patients than in the nonsarcopenic group. Preoperative sarcopenia and sarcopenic obesity were associated with shorter OS (p = 0.012 and p = 0.041, respectively), but not shorter DFS. Myosteatosis was neither associated with DFS nor OS. On multivariable analysis, sarcopenia was the only significant prognostic factor for OS (p = 0.039). Preoperative sarcopenia assessed by CT is a poor prognostic factor for OS in pancreatic cancer patients after PD. • Sarcopenia and sarcopenic obesity can be evaluated by abdominal CT on L3 level. • Patients with diabetes mellitus (DM) had lower sex-standardized subcutaneous adipose tissue area index and skeletal muscle density and higher visceral to subcutaneous adipose tissue area ratio than did those without DM. • Preoperative sarcopenia, sarcopenic obesity, and new-onset diabetes mellitus may predict poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy.