Factor In Pancreatic Cancer Patients Research Articles

Combination of neutrophil-to-lymphocyte ratio and serum CA 19-9 as a prognostic factor in pancreatic cancer.

Traditionally, serum carbohydrate antigen 19-9 (CA 19-9) has been used as a key biomarker for pancreatic cancer and recently other biomarkers which reflect the systemic immune and inflammatory responses also have been explored as potential prognostic factors. The study aims to evaluate the significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and serum CA 19-9 as prognostic factor in pancreatic cancer patients. A retrospective analysis was conducted in 153 consecutive patients with pancreatic cancer in Instituto Nacional de Cancerología from 2013 to 2018. Pretreatment NLR and serum CA 19-9 values were recorded as well as survivals. The cut-off value determined for NLR was 2.4 and for serum CA 19-9 was 553 U/mL. Survival analysis showed that the 5-year overall survival (OS) was 9% in patients with low-NLR compared with 2% for patients with high-NLR (P=0.008), and 5-year progression-free survival (PFS) was 5.7% in patients with low-NLR compared with 1.3% in patients with high-NLR (P=0.007). For patients with low-CA 19.9, 5-year OS was 8.5% compared with 0% for patients with high-CA 19-9 (P=0.002), and 5-year PFS was 4.1% in patients with low-CA 19-9 compared with 0% in patients with high-CA 19-9 (P=0.005). Classification groups created showed that 5-year OS in Group 1 (low-NLR and low-CA 19-9) was 11.8% compared with 1.9% for patients in Group 2 (either one or both high-NLR or CA 19-9) (P<0.001), and 5-year PFS was 8.6% in Group 1 and 0% in Group 2 (P=0.001). High-NLR and high-CA 19-9 values used separately are both independently associated with worse OS and PFS in patients with pancreatic cancer. The classification groups created combining both biomarkers showed better prognostic significance than when used separately as demonstrated by survival analysis and multivariate analysis.

374P Insights into treatment modalities and prognostic factors in pancreatic cancer patients: A 5-year real-world data analysis

374P Insights into treatment modalities and prognostic factors in pancreatic cancer patients: A 5-year real-world data analysis

Identification of a robust biomarker LAPTM4A for glioma based on comprehensive computational biology and experimental verification.

Glioma, a highly invasive and deadly form of human neoplasm, presents a pressing need for the exploration of potential therapeutic targets. While the lysosomal protein transmembrane 4A (LATPM4A) has been identified as a risk factor in pancreatic cancer patients, its role in glioma remains unexplored. The analysis of differentially expressed genes (DEG) was conducted from The Cancer Genome Atlas (TCGA) glioma dataset and the Genotype Tissue Expression (GTEx) dataset. Through weighted gene co-expression network analysis (WGCNA), the key glioma-related genes were identified. Among these, by using Kaplan-Meier (KM) analysis and univariate/multivariate COX methods, LAPTM4A emerged as the most influential gene. Moreover, the bioinformatics methods and experimental verification were employed to analyze its relationships with diagnosis, clinical parameters, epithelial-mesenchymal transition (EMT), metastasis, immune cell infiltration, immunotherapy, drug sensitivity, and ceRNA network. Our findings revealed that LAPTM4A was up-regulated in gliomas and was associated with clinicopathological features, leading to poor prognosis. Furthermore, functional enrichment analysis demonstrated that LATPM4A played a role in the immune system and cancer progression. In vitro experiments indicated that LAPTM4A may influence metastasis through the EMT pathway in glioma. Additionally, we found that LAPTM4A was associated with the tumor microenvironment (TME) and immunotherapy. Notably, drug sensitivity analysis revealed that patients with high LAPTM4A expression were sensitive to doxorubicin, which contributed to a reduction in LAPTM4A expression. Finally, we uncovered the FGD5-AS1-hsa-miR-103a-3p-LAPTM4A axis as a facilitator of glioma progression. In conclusion, our study identifies LATPM4A as a promising biomarker for prognosis and immune characteristics in glioma.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry pancreatic cancer subcohort

BackgroundThis substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients.MethodsThe Cancer-VTE Registry was an observational study that collected VTE data from patients with solid tumors across Japan. We measured baseline VTE prevalence, and at 1-year follow-up, the cumulative incidence of symptomatic and composite VTE (symptomatic VTE and incidental VTE requiring treatment), bleeding, cerebral infarction/transient ischemic attack (TIA)/systemic embolic event (SEE), and all-cause death.ResultsOf 1006 pancreatic cancer patients, 86 (8.5%) had VTE at baseline, and seven (0.7%) had symptomatic VTE. Significant risk factors of baseline VTE were Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, body mass index (BMI) ≥ 25 kg/m2, history of VTE, D-dimer > 1.2 µg/mL, and hemoglobin < 10 g/dL. At 1-year follow-up, the cumulative incidence of events was higher for pancreatic cancer vs other cancers. Pancreatic cancer patients with VTE vs those without VTE had significantly higher incidences of bleeding, cerebral infarction/TIA/SEE, and all-cause death. No significant risk factors for composite VTE were identified.ConclusionsThe cumulative incidence of composite VTE during cancer treatment was higher in pancreatic cancer than in other cancer types. Some risk factors for VTE prevalence at cancer diagnosis were identified. Although VTE prevalence at cancer diagnosis did not predict the subsequent 1-year incidence of composite VTE, it was a significant predictor of other events such as all-cause death in pancreatic cancer patients.Trial registrationUMIN Clinical Trials Registry; UMIN000024942

Prognostic value of albumin-bilirubin score in pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.

Objective: The current study aimed to investigate the prognostic value of albumin-bilirubin (ALBI) score in predicting clinical outcomes of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Methods: This retrospective study included 90 pancreatic cancer patients after pancreatoduodenectomy with liver metastasis from January 2012 to December 2018. In this study, the Chi-square or Fisher's exact tests, the receiver operating characteristic (ROC) curve, Kaplan-Meier method and Log-rank test, univariate and multivariate Cox proportional hazard regression analyses, nomogram, calibration curves and decision curve analysis were used for all statistical analysis. Results: We analyzed the optimal cut-off value of ALBI by ROC curve, and the optimal cut-off value was -2.60. According to ALBI score, these patients were divided into two groups: low ALBI group (n = 33) and high ALBI group (n = 57). Patients with low ALBI score was significantly related to longer progression free survival (PFS) (p = 0.0002, HR: 3.039, 95% CI: 1.772-5.210) and overall survival (OS) (p = 0.0005, HR: 2.697, 95% CI: 1.539-4.720). The 1-, 3-, and 5-year PFS and OS rates in low ALBI group were higher than those in high ALBI group. ALBI was a potential independent prognostic factor for pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation. Moreover, the nomogram was used to predict the 1-, 3-, and 5-year survival probabilities of PFS and OS. The calibration curve shown that the prediction line matched the reference line well for postoperative 3-year PFS and OS. The DCA shown that nomogram model was better than the only ALBI, and indicated the ability for clinical decision-making, especially in 1-year PFS, and 3-, 5-year OS. Conclusion: ALBI is a potential independent factor for PFS and OS, and can predict the prognosis of pancreatic cancer patients after pancreatoduodenectomy with liver metastasis following radiofrequency ablation.

Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection

Background The pretreatment albumin–globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. Methods We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin–globulin ratio (AGR) were calculated for each case. Results Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). Conclusion High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

Risk factors, prognostic predictors, and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis.

Liver metastasis (LM) remains a major cause of cancer-related death in patients with pancreatic cancer (PC) and is associated with a poor prognosis. Therefore, identifying the risk and prognostic factors in PC patients with LM (PCLM) is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients. However, there are limited data on risk and prognostic factors in PCLM patients. To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms. Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance, Epidemiology, and Results Database. Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode. The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model. The performance of the two nomogram models was evaluated using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and risk subgroup classification. The Kaplan-Meier method with a log-rank test was used for survival analysis. We enrolled 33459 patients with PC in this study. Of them, 11458 (34.2%) patients had LM at initial diagnosis. Age at diagnosis, primary site, lymph node metastasis, pathological type, tumor size, and pathological grade were identified as independent risk factors for LM in patients with PC. Age > 70 years, adenocarcinoma, poor or anaplastic differentiation, lung metastases, no surgery, and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM. The C- index of diagnostic and prognostic nomograms were 0.731 and 0.753, respectively. The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves, calibration plots, and DCA curves. The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation. Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention. External validation is required to confirm these results.

Dysfunctional epigenetic protein-coding gene-related signature is associated with the prognosis of pancreatic cancer based on histone modification and transcriptome analysis

Emerging evidence suggests that epigenetic alterations are responsible for the oncogenesis and progression of cancer. However, the role of epigenetic reprogramming in pancreatic cancer is still not clear. In this study, we used the limma R package to identify differentially expressed protein-coding genes (PCGs) between pancreatic cancer tissues and normal control tissues. The cell-type identification by the estimating relative subsets of RNA transcripts (CIBERSORT) package was used to quantify relative cell fractions in tumors. Prognostic molecular clusters were constructed using ConsensusClusterPlus analysis. Furthermore, the least absolute shrinkage and selection operator and stepAIC methods were used to construct a risk model. We identified 2351 differentially expressed PCGs between pancreatic cancer and normal control tissues in The cancer genome atlas dataset. Combined with histone modification data, we identified 363 epigenetic PCGs (epi-PCGs) and 19,010 non-epi-PCGs. Based on the epi-PCGs, we constructed three molecular clusters characterized by different expression levels of chemokines and immune checkpoint genes and distinct abundances of various immune cells. Furthermore, we generated a 9-gene model based on dysfunctional epi-PCGs. Additionally, we found that patients with high risk scores showed poorer prognoses than patients with low risk scores (p < 0.0001). Further analysis showed that the risk score was significantly related to survival and was an independent risk factor for pancreatic cancer patients. In conclusion, we constructed a 9-gene prognostic risk model based on epi-PCGs that might serve as an effective classifier to predict overall survival and the response to immunotherapy in pancreatic cancer patients.

FT3 to FT4 Conversion Ratio May Be an Independent Prognostic Factor in Pancreatic Cancer Patients.

Preclinical evidence suggests that T4 can promote tumor growth while T3 can act conversely; therefore, the fT3 and fT4 concentrations should affect overall survival (OS) in cancer patients. The objective of the study was to look for an association between thyroid hormone concentrations in peripheral blood and OS in the pancreatic adenocarcinoma (PDAC) patients group. We included, retrospectively, 15 PDAC patients, without thyroid dysfunction under treatment, who underwent radical surgery, with no prior history of anticancer therapy. TSH, fT3, and fT4 concentrations were determined in blood samples taken preoperatively. We found that the fT3/fT4 ratio categorized into two groups (&lt;0.22 vs. ≥0.22) dichotomized the study population into poor and good prognosis subgroups (log-rank p = 0.03; OS medians, respectively: 3 and 14 months), being a statistically significant predictor both in uni- and multivariate Cox regression analysis. We conclude that the importance of fT4 into fT3 conversion means not just its standard metabolic effects as the final products of thyroid gland activity. We hypothesize that it is linked to the progression of pancreatic malignancies, either via thyroid hormone receptors or indirectly, by interaction with cancer cells product.

Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer.

The aim of this study is to identify cuproptosis-related lncRNAs and construct a prognostic model for pancreatic cancer patients for clinical use. The expression profile of lncRNAs was downloaded from The Cancer Genome Atlas database, and cuproptosis-related lncRNAs were identified. The prognostic cuproptosis-related lncRNAs were obtained and used to establish and validate a prognostic risk score model in pancreatic cancer. In total, 181 cuproptosis-related lncRNAs were obtained. The prognostic risk score model was constructed based on five lncRNAs (AC025257.1, TRAM2-AS1, AC091057.1, LINC01963, and MALAT1). Patients were assigned to two groups according to the median risk score. Kaplan-Meier survival curves showed that the difference in the prognosis between the high- and low-risk groups was statistically significant. Multivariate Cox analysis showed that our risk score was an independent risk factor for pancreatic cancer patients. Receiver operator characteristic curves revealed that the cuproptosis-related lncRNA model can effectively predict the prognosis of pancreatic cancer. The principal component analysis showed a difference between the high- and low-risk groups intuitively. Functional enrichment analysis showed that different genes were involved in cancer-related pathways in patients in the high- and low-risk groups. The risk model based on five prognostic cuproptosis-related lncRNAs can well predict the prognosis of pancreatic cancer patients. Cuproptosis-related lncRNAs could be potential biomarkers for pancreatic cancer diagnosis and treatment.

Predicting the Overall Survival in Patients with Advanced Pancreatic Cancer by Calculating L3 Skeletal Muscle Index Derived from CT.

Pancreatic cancer is mostly diagnosed in advanced stages, and treatment results are not satisfactory. L3 skeletal muscle index (SMI) has emerged as a prognostic factor in pancreatic cancer patients. We aimed to assess the association between sarcopenia and overall survival in patients with pancreatic cancer in this study. Patients who were admitted to the Department of Oncology between March 2012 and December 2019 and diagnosed with pancreatic cancer were evaluated. The computerized tomography images and laboratory parameters of a total of 115 patients were included in this retrospective singlecenter study. We defined sarcopenia as an SMI <43,56 cm²/m² for females and <56,44 cm²/m² for males using the receiver operating characteristics (ROC) curve in the study population. Univariate and multivariate analyses were performed by using Cox-regression modelling, and survival curves were constructed by using Kaplan-Meier method. 70% of the patients were male, and the mean age was 64.9±9.9 years (mean ± SD). 70.6% of female patients and 67.9% of male patients were diagnosed with stage 4 cancer. The prevalence of sarcopenia in the whole patient group was 29.6%. By multivariate analysis, SMI (p=0.009) and advanced stage (p=0.003) were found as poor prognostic factors for overall survival (OS). The neutrophil to lymphocyte ratio (NLR) was statistically significantly higher in sarcopenic patients than in nonsarcopenic patients (p=0.031). Patients having sarcopenia at the time of diagnosis may demonstrate poorer overall survival of pancreatic cancer, and SMI may be considered as a potential prognostic factor.

Histological tumor necrosis in pancreatic cancer after neoadjuvant therapy.

The pathological prognostic factors in pancreatic cancer patients who have received neoadjuvant therapy (NAT) are still elusive. The aim of the present study was to investigate the prognostic potential of histological tumor necrosis (HTN) in patients who received NAT and to evaluate tumor changes after NAT. HTN was studied in 44 pancreatic cancer patients who received NAT followed by surgery (NAT group) compared with 263 patients who received upfront surgery (UFS group). The prognostic factors in the NAT group were analyzed, and carbonic anhydrase 9 (CA-9) expression was compared between the NAT and USF group to evaluate the hypoxic microenvironment changes during NAT. HTN was found in 15 of 44 patients in the NAT group, and its frequency was lower than that in the UFS group (34 vs. 51%, P=0.04). Cox proportional hazards models identified HTN as an independent risk factor for relapse-free survival in the NAT group [risk ratio (RR), 5.60; 95% confidence interval (CI): 2.27-14.26, P<0.01]. Significant correlations were found between HTN and CA-9 expression both in the NAT and UFS groups (P<0.01 for both). CA-9 expression was significantly upregulated in the NAT group overall, although this upregulation was specifically induced in patients without HTN. In conclusion, HTN was a poor prognostic factor in pancreatic cancer patients receiving NAT followed by surgery, and the present study suggests a close association between HTN and tumor hypoxia. Increased hypoxia after NAT may support the thesis for re-engineering the hypoxia-alleviating tumor microenvironment in NAT regimens for pancreatic cancer.

Clinical Analysis of Bloodstream Infection of Escherichia coli in Patients with Pancreatic Cancer from 2011 to 2019.

Background Pancreatic cancer patients were particularly predisposed to develop Escherichia coli (E. coli) bloodstream infection (BSI); however, little information is currently available. We set out to find E. coli BSI's risk factors in pancreatic cancer to provide valuable experience. Methods We retrospectively analyzed the clinical data of pancreatic cancer patients (31 cases with E. coli BSI and 93 cases without BSI) by a case-control study. SPSS 17.0 was adopted to perform univariate and multivariate analyses. Bacterial resistance analysis was performed by Whonet 5.6. Results Hospitalization days ≥7 days, number of admissions ≥2 times, surgery, chemotherapy, the type of antibiotics used ≥2 species, albumin<40.0 g/L, and prealbumin < 0.2 g/L were the potential risk factors for pancreatic cancer patients with E. coli BSI (P < 0.1). Multivariate logistic regression showed hospitalization days ≥7 days (OR = 11.196, 95% CI = 0.024–0.333, P < 0.001), surgery (OR = 32.053, 95% CI = 0.007–0.137, P < 0.001), and chemotherapy (OR = 6.174, 95% CI = 0.038–0.688, P=0.014) were the independent risk factors for E. coli BSI of pancreatic cancer patients. E. coli resistant to carbapenems was rare; they were susceptible to cephamycin and piperacillin/tazobactam. The 90-day mortality rate of the infected group was significantly higher than the control group (41.9% versus 8.6%, P < 0.001). Conclusions Hospitalization days ≥7 days, surgery, and chemotherapy are the independent risk factors for E. coli BSI of pancreatic cancer patients, which allows us to identify patients at potential risk and perform preventive treatment in time.

Impact of nuclear factor of activated T cells (NFAT) families as a poor prognostic factor in pancreatic cancer patients.

584 Background: Pancreatic cancer microenvironment is crucial in cancer development, and cancer-stromal interactions have been recognized as important targets for cancer therapy. Nuclear factor of activated T-cells (NFAT) has been found in T cells as a transcriptional activator of IL-2, and known to be involved in various processes including the immune system. In cancer tissues, NFAT has been reported to be involved in metastasis. In breast and colorectal cancers, NFATc2 and NFAT5 have been reported to interact with integrins to promote cancer cell migration. On the other hand, in pancreatic cancer, NFAT5 has been reported to be a poor prognostic factor via regulation of PGK1 transcription. In the present study, we evaluated the expression of NFATc2 and NFAT5 in pancreatic cancer and examined their relationship with prognosis. Methods: One hundred and sixty five pancreatic cancer patients who underwent curative-intrent resection at our hospital between 2010 and 2020 were included in this study. We performed immunostaining for NFATc2 and NFAT5 using the tissue micro array. We evaluated the expression of NFATc2 and NFAT5 protein and examined their correlation with clinicopathological factors. Results: Of the 165 pancreatic cancer cases, we detected increased NFATc2 protein expression in cytoplasm of cancer cells in 53 cases (32.1%) and NFAT5 in 104 cases (63.0%), and NFATc2/NFAT5 co-expression in 43 cases (26.1%). NFATc2 expression was not correlated with any clinicopathological factors, NFAT5 expression was correlated with venous invasion (p = 0.047), and NFATc2/NFAT5 co-expression was slightly correlated with Stage (p = 0.054). Relapse free survival (RFS) was estimated in all 165 patients. There was no significant difference for RFS in either NFATc2-high group or NFAT5-high group (p = 0.314 or p = 0.574), however, NFATc2/NFAT5 co-expression group showed significantly poor RFS (p = 0.023). Overall survival (OS) was also estimated in all 165 patients. There was no significant difference for OS in either NFATc2-high group or NFAT5-high group (p = 0.146 or p = 0.529), however, NFATc2/NFAT5 co-expression group showed significantly poor survival (p = 0.006). In multivariate analysis, lymphatic invasion, curability and NFATc2/NFAT5 co-expression were independent prognostic factors for RFS, and lymphatic invasion, curability, presence of adjuvant therapy and NFATc2/NFAT5 co-expression were independent prognostic factors for OS. Conclusions: In pancreatic cancer, NFATc2/NFAT5 co-expression was suggested to be involved in the critical process of pancreatic cancer progression, and may be a novel therapeutic target.

Prognostic value of Gustave Roussy immune score in operable pancreatic adenocarcinoma.

The Gustave Roussy immune score (GRIm score) is a laboratory index developed to predict survival in nonsmall cell lung cancer patients undergoing immunotherapy and has shown that the pretreatment value is an independent prognostic factor for survival. In this study, we aimed to determine prognostic significance of GRIm score for pancreatic adenocarcinoma that have not been determined in the literature for pancreatic cancer before. The reason for choosing this scoring is to show that the immune scoring system works as a prognostic marker in pancreatic cancer known as immune-desert tumor via immune properties of microenvironment. Medical records of patients with histologically confirmed pancreatic ductal adenocarcinoma, who were treated and followed up between December 2007 and July 2019 at our clinic, were reviewed retrospectively. GRIm scores of each patient were calculated at the time of diagnosis. Survival analysis were performed according to risk groups. A total of 138 patients were included in the study. While 111 (80.4%) patients were in the low-risk group; 27 (19.6%) were in high-risk group according to GRIm score. Median OS was 36.9 months (95% Confidence interval (CI): 25.42-48.56) in lower GRIm scores, and it was 11.1 months (95% CI: 6.83-15.44) in higher GRIm scores (P = 0.002). One-two-three-year OS rates were 85% versus 47%, 64% versus 39%, 53% versus 27% for low versus high GRIm scores, respectively. The multivariate analysis revealed that high GRIm score was an independent poor prognostic factor. GRIm can be used as a noninvasive, easily applicable, practical prognostic factor in pancreatic cancer patients.

Combining CRP and CA19-9 in a novel prognostic score in pancreatic ductal adenocarcinoma

Inflammation promotes tumor progression, induces invasion and metastatic spread. This retrospective study explored CRP, CA19-9, and routine laboratory values as preoperative prognostic factors in pancreatic cancer patients. Between 2000 and 2016, there were 212 surgically treated pancreatic cancer patients at Helsinki University Hospital, Finland. Out of these, 76 borderline resectable patients were treated with neoadjuvant therapy (NAT); 136 upfront resected patients were matched for age and sex at a 1:2 ratio. We analyzed preoperative CRP, CA19-9, CEA, leukocytes, albumin, bilirubin and platelets. CRP and CA19-9 were combined into a prognostic score: both CRP and CA19-9 below the cut-off values (3 mg/l and 37 kU/l, respectively), either CRP or CA19-9 above the cut-off value, and finally, both CRP and CA19-9 above the cut-off values. Among all patients, median disease-specific survival times were 54, 27 and 16 months, respectively (p < 0.001). At 5 years, among patients with CRP and CA19-9 levels below the cut-off values, 49% were alive and 45% were disease-free. Among NAT patients the corresponding survival rates were 52% and 45% and among those undergoing upfront surgery 45% and 40%, respectively. This novel prognostic score combining CRP and CA19-9 serves as a useful preoperative tool estimating survival.

Prognostic Values of SUVmax Value of PET/CT and CA19-9 as Biologic Markers in Patients with Pancreatic Ductal Adenocarcinoma

Among various prognostic factors of pancreatic cancer, most of clinical information before surgery is obtained by imaging modality. However tumor biologic characteristics also should be considered to decide treatment plan. Purpose of this study is to evaluate clinical usefulness of preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography and carbohydrate antigen as biologic markers for prognosis of resectable pancreatic ductal adenocarcinoma. 189 patients with pancreatic adenocarcinoma underwent preoperative FDG-PET testing were studied. SUVmax was calculated for each primary lesion. Patients who underwent neoadjuvant chemotherapy, R2 resection, and sequential resection were excluded. Analysis about correlation between SUVmax and clinicopathologic parameters was performed. C-tree statistical method was drawn to estimated cutoff values of SUVmax and CA19-9 for survival rate. Multivariate analysis was conducted to identify prognostic factors for overall survival. Median duration of overall survival was 26 months, five-year survival rate was 22.4%. C-tree analysis revealed the optimal cutoff values for SUVmax was 5.5 and that of CA19-9 was 150 about survival rate. When subjects were divided into three groups according to combination of SUVmax and CA19-9 values from C-tree (high group, SUVmax >5.5 and CA19-9>150, intermediate group and low group, SUVmax≤5.5 and CA19-9≤150), there was a significant 5YSR difference (5.6%, 24.3% and 36.5%, p < 0.001) The multivariate analysis revealed low BMI and high SUVmax and venous invasion were prognostic factor in overall survival. As biologic markers, SUVmax and CA19-9 are prognostic factors in pancreatic cancer patients. Especially, patients with high SUVmax and CA19-9 are not indication to upfront sugery.

The Risk Factors of Pancreatic Cancer Patients in Dr. Cipto Mangunkusumo National Hospital, Jakarta During 2014-2019

Background: Pancreatic cancer is a very rare cancer with age-adjusted rates ranging from about 5 to 10 new cases per 100,000 persons per year. It has one of the worst prognoses of any type of cancer, with a 5-year survival rate of only 4.6%. Several risk factors have been identified, including older age, smoking, familial history of pancreatic cancer, obesity, chronic pancreatitis, diabetes mellitus, and alcohol consumption.Method: This was a descriptive study describing the risk factors of patients who were diagnosed with pancreatic cancer in the period between 1 January 2014 – 1 January 2019 at the Cipto Mangunkusumo National Referral Hospital (RSCM) Jakarta. Data were obtained from the medical records and Endoscopic Retrograde Cholangiopancreatography (ERCP) database from the RSCM Gastrointestinal Endoscopy Center.Results: From January 2014 to January 2019 there were 123 patients with newly diagnosed pancreatic cancer in RSCM. The mean age was 52 years old. The incidence of pancreatic cancer is more common in men (53%) than women (47%). The most common risk factor identified is smoking which was found in 29% of patients, followed by obesity at 27.9% and a history of diabetes mellitus at 19.5%. Risk factors with a fairly low prevalence include alcohol consumption at 9.7% and chronic pancreatitis at 2.4%. No family history of pancreatic cancer is identified in any subject.Conclusion: Smoking, obesity, and diabetes mellitus are common risk factors in pancreatic cancer patients. In contrast, chronic pancreatitis, alcohol consumption, and family history of pancreatic cancer are less commonly identified in patients.

The relationship between the index of lymph node metastasis and the prognosis of pancreatic cancer patients after R0 resection

Objective: To investigate the prognostic values of three different staging schemes including the number of lymph node metastasis (N stage), lymph node ratio (LNR) and log odd of positive lymph nodes (LODDS) in pancreatic cancer patients after R0 resection. Methods: The clinical and pathological data of 307 pancreatic cancer patients who underwent R0 resection at Cancer Hospital of Chinese Academy of Medical Sciences from January 2010 to December 2018 were retrospectively analyzed. Kaplan-Meier and Cox proportional hazard regression models were used to analyze the independent prognostic factors. The area under the receiver operator characteristic curve (AUC) was used to compare the prognostic efficacy of different lymph node staging systems. Results: The median survival was 24.0 months, 1-year, 3-year, and 5-year survival rates were 72.0%, 35.5% and 24.0%, respectively. Multivariate analysis showed that CA199, differentiation, T stage, adjuvant therapy, N stage, LNR stage, and LODDS stage were independent prognostic factors for pancreatic cancer patients after R0 resection (P<0.05). The AUC values of the 1-year survival rate for N stage, LNR stage, and LODDS stage were 0.591, 0.592 and 0.609, respectively. The AUC values of the 3-year survival rate for N stage, LNR stage, and LODDS stage were 0.585, 0.588 and 0.593, respectively. The AUC values of the 5-year survival rate for N stage, LNR stage, and LODDS stage were 0.554, 0.557 and 0.589, respectively. The AUC values of the LODDS stage were the highest while the N stage were the lowest, but there was no significant difference among these three systems (P>0.05). For all patients, the LODDS staging system was slightly better than the N and LNR staging systems, but the difference was not statistically significant (P>0.05). For patients with N0 stage, the LODDS staging system showed better prediction performance than the N stage and LNR staging systems (P<0.05). Conclusions: The N stage, LNR stage, and LODDS stage are independent prognostic factors for pancreatic cancer patients after R0 resection. For patients without lymph node metastasis, LODDS staging system is superior to N and LNR staging systems in predicting prognosis.

HMGA2 Antisense Long Non-coding RNAs as New Players in the Regulation of HMGA2 Expression and Pancreatic Cancer Promotion.

Background: Natural antisense long non-coding RNAs (lncRNAs) are regulatory RNAs transcribed from the opposite strand of either protein coding or non-coding genes, able to modulate their own sense gene expression. Hence, their dysregulation can lead to pathologic processes. Cancer is a complex class of diseases determined by the aberrant expression of a variety of factors, among them, the oncofetal chromatin architectural proteins High Mobility Group A (HMGA) modulate several cancer hallmarks. Thus, we decided to investigate the presence of natural antisense lncRNAs in HMGA1 and HMGA2 loci, and their possible involvement in gene expression regulation.Methods: We used FANTOM5 data resources, FANTOM-CAT genome browser and Zenbu visualization tool, which employ 1,829 human CAGE and RNA-sequencing libraries, to determine expression, ontology enrichment, and dynamic regulation of natural antisense lncRNAs in HMGA1 and HMGA2 loci. We then performed qRT-PCR in different cancer cell lines to validate the existence of HMGA2-AS1 transcripts. We depleted HMGA2-AS1 transcripts with siRNAs and investigated HMGA2 expression by qRT-PCR and western blot analyses. Moreover, we evaluated cell viability and migration by MTS and transwell assays, and EMT markers by qRT-PCR and immunofluorescence. Furthermore, we used bioinformatics approaches to evaluate HMGA2 and HMGA2-AS1 correlation and overall survival in tumor patients.Results: We found the presence of a promoter-associated lncRNA (CATG00000088127.1) in the HMGA1 gene and three antisense genes (RPSAP52, HMGA2-AS1, and RP11-366L20.3) in the HMGA2 gene. We studied the uncharacterized HMGA2-AS1 transcripts, validating their existence in cancer cell lines and observing a positive correlation between HMGA2 and HMGA2-AS1 expression in a cancer-derived patient dataset. We showed that HMGA2-AS1 transcripts positively modulate HMGA2 expression and migration properties of PANC1 cells through HMGA2. In addition, Kaplan-Meier analysis showed that high level of HMGA2-AS1 is a negative prognostic factor in pancreatic cancer patients.Conclusions: Our results describe novel antisense lncRNAs associated with HMGA1 and HMGA2 genes. In particular, we demonstrate that HMGA2-AS1 is involved in the regulation of its own sense gene expression, mediating tumorigenesis. Thus, we highlight a new layer of complexity in the regulation of HMGA2 expression, providing new potential targets for cancer therapy.