Prognosis Of Pancreatic Adenocarcinoma Patients Research Articles

TRNA-derived RNA fragment, tRF-18-8R6546D2, promotes pancreatic adenocarcinoma progression by directly targeting ASCL2

Pancreatic adenocarcinoma (PAAD) is a life-threatening cancer. Exploring new diagnosis and treatment targets helps improve its prognosis. tRNA-derived small non-coding RNAs (tsRNAs) are a novel type of gene expression regulators and their dysregulation is closely related to many human cancers. Yet the expression and functions of tsRNAs in PAAD are not well understood. Our study used RNA sequencing to identify tsRNA expression profiles in PAAD cells cultured in no or high glucose media and found tRF-18-8R6546D2 was an uncharacterized tsRNA, which has significantly high expression in PAAD cells and tissues. Clinically, tRF-18-8R6546D2 is linked to poor prognosis in PAAD patients and can be used to distinguish them from healthy populations. Functionally, in vitro and vivo, tRF-18-8R6546D2 over-expression promoted PAAD cell proliferation, migration and invasion, inhibited apoptosis, whereas tRF-18-8R6546D2 knock-down showed opposite effects. Mechanistically, tRF-18-8R6546D2 promoted PAAD malignancy partly by directly silencing ASCL2 and further regulating its downstream genes such as MYC and CASP3. These findings show that tRF-18-8R6546D2 is a novel oncogenic factor and can be a promising diagnostic or prognostic biomarker and therapeutic target for PAAD.

Integrated analysis identifies cuproptosis-related gene DLAT and its competing endogenous RNAs network to predict the prognosis of pancreatic adenocarcinoma patients.

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with poor prognosis. However, the relationship between cuproptosis-related genes (CRGs) and its competing endogenous RNA (ceRNA) network with the prognosis of PAAD patients remains unclear. To investigate this relationship, we calculated the difference in CRGs between PAAD tissues and normal tissues using the 'limma' R package. Additionally, we employed least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a prognostic signature for CRGs. Survival analysis of patients with PAAD was performed using Kaplan-Meier analysis. Furthermore, we used bioinformatics tools to screen for CRGs-related MicroRNA (miRNA) and lncRNAs. To validate these findings, we conducted real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, colony formation, and Transwell assays to assess the effect of DLAT in vitro. Our results revealed a cuproptosis-related prognostic signature consisting of 3 prognostic genes (DLAT, LIAS, and LIPT1). Notably, patients with a high-risk score for the CRGs signature exhibited poor prognosis in terms of overall survival (OS) (P < .05). The receiver operating characteristic (ROC) curve was used to evaluate the prognostic signature of CRGs. The results showed that the 1-year, 3-year, and 5-year area under the curve values for predicting OS were 0.62, 0.66, and 0.79, respectively. Additionally, the CRGs-related ceRNA network revealed the regulatory axis of LINC00857/has-miR-1179/DLAT in PAAD. In vitro experiments demonstrated that knockdown of LINC00857 and DLAT inhibited the growth and invasion of PAAD cells. This study identified a CRG-related prognostic signature consisting of 3 biomarkers (DLAT, LIAS, and LIPT1) for PAAD. Furthermore, ceRNA network analysis suggested the involvement of the LINC00857/has-miR-1179/DLAT axis in the development of PAAD. Overall, this study provides theoretical support for the investigation of diagnostic and prognostic biomarkers as well as potential therapeutic targets in PAAD.

A study on the role of Taxifolin in inducing apoptosis of pancreatic cancer cells: screening results using weighted gene co-expression network analysis.

Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.

Identification and validation of a novel anoikis-related long non-coding RNA signature for pancreatic adenocarcinoma to predict the prognosis and immune response.

To provide more precise treatment options for pancreatic adenocarcinoma (PAAD) patients and improve their prognosis,we established a novel anoikis-related long non-coding RNA signature (ARLSig) to predict the prognosis and immune response for PAAD patients. We downloaded information on PAAD from The Cancer Genome Atlas (TCGA) database, and screened long non-coding RNA (lncRNA) linked with anoikis, and prognostic signatures with these lncRNAs. After that, ARLSig was verified using receiver operating characteristic (ROC) and C-index curves. To further investigate the role of ARLSig, we also performed enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Additionally, using immunological correlation analysis and single-sample genetic enrichment analysis, we investigated the effectiveness of PAAD immunotherapy. We screened 7 lncRNAs to construct a novel ARLSig and utilized it to predict the efficacy of immunotherapy and the prognosis of PAAD patients. ARLSig can identify patients who will benefit from immunotherapy and improve the prediction of PAAD patient prognosis.

Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of PPM1K in the Tumor Microenvironment.

Early metastasis and resistance to traditional therapy are responsible for the poor prognosis of pancreatic adenocarcinoma patients. Metal-dependent protein phosphatases (PPMs) have been proven to play a crucial role in the initiation and progression of various tumors. Nevertheless, the expression and function of distinct PPMs in pancreatic adenocarcinoma have not been fully elucidated. In this study, we investigated the mRNA expression level, prognostic value, and the relationship between the expression of PPMs and the tumor microenvironment in pancreatic adenocarcinoma using Oncomine, TCGA and GTEx, GEO, Kaplan-Meier plotter, STRING, GeneMANIA, and HPA databases and R packages. GO and KEGG analysis revealed that PPMs and their differential co-expression genes are attributed to cell-cell adhesion and immune cell infiltration. Among these, PPM1K was downregulated in the tissue and peripheral blood of PAAD patients, whose expression level was negatively related to poor prognosis. Further to this, PPM1K was found to play a role in the epithelial-mesenchymal transition and immune infiltration. ROC curves showed that PPM1K had a good predictive value for pancreatic adenocarcinoma. The knockdown of PPM1K markedly promoted the proliferation and migration of pancreatic cancer cells, confirming its role in tumor suppressor activity in PAAD. This study demonstrates the potential clinical utility of PPM1K in tumor immunotherapy and brings about novel insights into the prognostic value of PPM1K in pancreatic adenocarcinoma.

An Aggrephagy-Related LncRNA Signature for the Prognosis of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50).

Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) has a high degree of malignancy and a very poor prognosis, and the 5-year overall survival rate of patients is approximately 7%. To improve the prognosis of patients with PAAD, a more comprehensive and in-depth study of the pathogenesis of PAAD and the identification of new diagnostic markers and treatment targets are urgently needed. Increasing evidence supports that the small ubiquitin-like modifier (SUMO) family is closely related to the occurrence and development of a variety of cancers. However, the function of the SUMO family in PAAD is not clear, and related research is very scarce. Methods: R, Cytoscape, cBioPortal, and other software and online databases were used to comprehensively analyze the expression characteristics, prognostic value, and oncogenic mechanism of the SUMO family in PAAD. Results: SUMO family members are highly expressed in PAAD, and high expression of SUMO family members is significantly associated with poor clinicopathological features and poor prognosis in PAAD patients. In addition, SUMO family members are significantly coexpressed with M6A methylation regulators and various oncogenes and play an activating role in various oncogenic pathways, including EMT. Furthermore, it is worth noting that the close association between SUMO family members and TP53 mutation status and the negative regulatory effect of SUMO1/2 on PAAD immunity may represent the potential mechanism by which SUMO family members promote the development of PAAD. Moreover, the coexpression characteristics of SUMO family members and a variety of cancer-promoting immune checkpoint genes, as well as the positive correlation between SUMO4 expression level and the sensitivity of various targeted or chemotherapeutic drugs, including gemcitabine, paclitaxel, and doxorubicin, suggest future clinical directions of this study. Conclusion: The SUMO family is closely related to the occurrence and development of PAAD and can be used as a new biomarker and therapeutic target for patients with PAAD.

Prognostic value, immune signature and molecular mechanisms of the APOBEC family members APOBEC1, APOBEC3A, APOBEC3G and APOBEC3H in pancreatic adenocarcinoma.

Background: Increasing evidence supports that the APOBEC family is associated with development of a variety of cancers. However, the function of APOBEC1/3A/3G/3H in pancreatic adenocarcinoma (PAAD) is still unclear. Methods: Comprehensive bioinformatic analysis using R (version 3.6.3), TISIDB, Metascape etc. were performed to study the clinicopathological characteristics, prognostic value, immune features and functional mechanisms of the APOBEC1/3A/3G/3H in PAAD. Results: APOBEC1/3A/3G/3H showed significantly elevated expression in PAAD than para-cancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of APOBEC1/3A/3G/3H in the immune regulation is diverse and complex, the high expression of APOBEC1 may inhibit the infiltration level of many kinds of immunoreactive tumor-infiltrating cells, which may be an important factor leading to immune escape of PAAD cells. Mechanistically, APOBEC1/3A/3G/3H played an activating role in multiple oncogenic pathways, including the EMT, RAS/MAPK and TSC/mTOR pathways. Moreover, we found that the expression level of APOBEC3G was positively correlated with the sensitivity of gemcitabine and doxorubicin. Conclusion: APOBEC1/3A/3G/3H play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets.

Suppression of rhomboid domain-containing 1 produces anticancer effects in pancreatic adenocarcinoma through affection of the AKT/GSK-3β/β-catenin pathway.

The protumor role of rhomboid domain-containing 1 (RHBDD1) has been observed in multiple cancers. However, the relationship between RHBDD1 and pancreatic adenocarcinoma has not been addressed. This project focused on the potential relevance of RHBDD1 in pancreatic adenocarcinoma. Bioinformatic analysis by publicly available data revealed that RHBDD1 was abundantly expressed in pancreatic adenocarcinoma. We further verified that RHBDD1 was expressed highly in clinical specimens of pancreatic adenocarcinoma. The Kaplan-Meier curve demonstrated that high-RHBDD1 expression was associated with poor prognosis in pancreatic adenocarcinoma patients. The functional studies revealed that depletion of RHBDD1 produced in vitro anticancer effects in pancreatic adenocarcinoma cells, including retardation of proliferation, reduction of metastatic potential, and induction of cell-cycle arrest at the G0/G1 phase and apoptosis. Mechanistic studies indicated that loss of RHBDD1 affected the activation of β-catenin via regulation of AKT. Forced expression of β-catenin reversed the RHBDD1-loss-induced anticancer effects in pancreatic adenocarcinoma cells. Crucially, depletion of RHBDD1 retarded the growth of pancreatic adenocarcinoma xenografts in vivo, a phenomenon associated with the AKT/β-catenin pathway. Collectively, these findings delineated that restraint of RHBDD1 displayed remarkable anticancer effects in pancreatic adenocarcinoma by affecting the AKT/β-catenin pathway. Our work unveils a pivotal role of RHBDD1 in pancreatic adenocarcinoma and proposes it as a novel candidate target for anticancer therapy of pancreatic adenocarcinoma.

KRT7 Overexpression is Associated with Poor Prognosis and Immune Cell Infiltration in Patients with Pancreatic Adenocarcinoma.

BackgroundPancreatic adenocarcinoma (PAAD) is a deadly tumor with a high recurrence rate and poor prognosis. Keratin 7 (KRT7) is a member of the keratin gene family that is involved in the regulation of cell growth, migration and apoptosis in many cancers. However, the role of KRT7 and its biological functions in PAAD remain unclear. We systemically analyzed the expression and clinical values of KRT7 in PAAD.MethodsThe Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Human Protein Atlas (HPA) databases were used to analyze the mRNA and protein expression of KRT7 in PAAD. The prognosis and subgroup analysis of KRT7 in PAAD patients was performed using the GEPIA, PROGgeneV2 and UALCAN databases. Later, the correlation between KRT7 expression and tumor immune molecules in PAAD was evaluated using the Immune Cell Abundance Identifier (ImmuCellAI) and TISIDB databases. Finally, the functional enrichment pathway of KRT7 and its coexpressed genes were analyzed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape databases and Gene Set Enrichment Analysis (GSEA).ResultsThe mRNA and protein expression of KRT7 was increased in PAAD tissues compared with normal tissues. High KRT7 expression was closely associated with tumor grade, TP53 mutations and poor prognosis in PAAD patients. Cox regression analysis proved that overexpressed KRT7 was an important and independent risk factor for poor overall survival (P = 0.006, HR =1.87) and disease-free survival (P = 0.019, HR =1.793) in PAAD. Additionally, KRT7 expression was significantly associated with immune infiltration of tumor immune cells and immunomodulators. Functional enrichment analyses and GSEA indicated that KRT7 might be involved in the regulation of the p53 pathway in PAAD.ConclusionOverexpressed KRT7 could be a promising prognostic and therapeutic target biomarker for PAAD by bioinformatics analysis.

Molecular subtypes of pancreatic adenocarcinoma stratified based on copy number variation profile.

e16232 Background: Pancreatic adenocarcinoma (PAAD) is one of the most lethal carcinomas all over the world, with an estimate of 60,430 new cases and 48,220 deaths in United States according to the cancer statistics of 2021. It is important and urgent to identify molecular subtypes for stratifying PAAD into different groups with respective genomic footprint, appropriate treatment and prognosis status. Methods: We profiled a comprehensive landscape of genomic alterations for 608 PAAD patients in a Chinese cohort, including somatic mutations, pathogenic germline variants and copy number variations (CNVs). 233 out of 608 PAAD had disease-free survival (DFS) information with at least 6-month follow-up. Focusing on this subset of PAAD, we explored prognostic values for several kinds of genomic alterations and finally identified four molecular subtypes based on CNV profile. Results: For point mutations in highly mutated genes ( KRAS, TP53, CDKN2A and SMAD4) or homologous recombination repair (HRR) genes ( ATM, ATR, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, NBN, PALB2, RAD50/ 51B/ 51C/ 51D/54L and MRE11A), we found no associations between them and prognosis of PAAD patients. Instead, PAAD could be stratified into four molecular subtypes based on CNV profile through unsupervised clustering and CNV score defined by principle component analysis (PCA). According to amplification and deletion pattern of genes in DNA repair and receptor tyrosine kinase related signaling pathways, we named these four subtypes as repair-deficient, proliferation-active, repair-proficient and repair-enhanced ones. Among them, repair-deficient PAAD had the best prognosis with median DFS of 410 days, repair-proficient and proliferation-active one had median DFS of 239 and 197 days, respectively, while repair-enhanced one had the worst prognosis with DFS of 48 days. Genomic footprint analysis showed that both of repair-deficient and proliferation-active subtypes of PAAD possessed higher copy number instability (CNI), while both of repair-proficient and repair-enhanced subtypes possessed higher tumor mutational burden (TMB), implying that the former two subtypes suited for DNA damage therapies (such as platinum-based chemotherapy and PARPi) and the latter two subtypes suited for immunotherapy. Conclusions: We identified four molecular subtypes for PAAD based on CNV profile and found their respective genomic footprint, suited treatment and prognosis status, pacing key steps to precision medicine in PAAD field.

LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma

BackgroundIt has been reported that the lncRNA SNHG16 has significantly increased expression in pancreatic adenocarcinoma (PC). However, the functions and mechanisms of SNHG16 are not clear. The aim of this study was to explore the effects of SNHG16 on PC.MethodsqRT-PCR analysis was applied to detect the expression levels of SNHG16, miR-302b-3p and SLC2A4 in PC tissues and cells. CCK8 and EdU assays were used to evaluate the proliferation of PC cells. Transwell assays were used to assess PC cell migration and invasion. Apoptosis was evaluated by flow cytometry, and the expression of apoptosis-related proteins (including Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9) was tested by western blotting. The interactions between miR-302b-3p and SNHG16 or miR-302b-3p and the 3’UTR of SLC2A4 mRNA were clarified by a dual luciferase reporter assay and RNA immunoprecipitation.ResultsSNHG16 expression was significantly elevated in PC tissues and cell lines and was associated with poor prognosis of PC patients. Knockdown of SNHG16 reduced PC cell proliferation, migration and invasion. SNHG16 acted as a sponge to regulate miR-302b-3p expression in PC cells. In addition, miR-302b-3p targeted SLC2A4 directly.ConclusionsSNHG16 promoted the progression of PC via the miR-302b-3p/SLC2A4 axis and was expected to be a potential target for the early diagnosis and treatment of PC.

LINC01232 Sponges Multiple miRNAs and Its Clinical Significance in Pancreatic Adenocarcinoma Diagnosis and Prognosis.

Background:Long noncoding RNAs have been demonstrated to play important roles in different kinds of human malignancy. The purpose of this study was to evaluate the diagnostic and prognostic value of long intergenic non-protein coding RNA 1232 (LINC01232) in patients with pancreatic adenocarcinoma (PAAD) and further explore the clinical significance of the potential miRNAs that might be sponged by LINC01232.Methods:The potential target miRNAs that might be sponged by LINC01232 were analyzed using bioinformatics analysis. The Real-Time quantitative PCR was adopted to measure the relative expression of LINC01232 and target miRNAs in PAAD serum and tissue samples. The diagnostic and prognostic value of LINC01232 was evaluated using the receiver operating characteristic analysis and Kaplan-Meier survival analysis, respectively.Results:LINC01232 expression was upregulated in PAAD serum and tissues and associated with patients’ TNM stage. Serum LINC01232 expression had diagnostic value, and the high levels of LINC01232 could predict unfavorable prognosis in PAAD patients. miR-204-5p, miR-370-5p and miR-654-3p were proposed as 3 targets of LINC01232 in PAAD, and their decreased expression levels in PAAD patients showed certain clinical significance in diagnosis and prognosis.Conclusion:The data of this study revealed that LINC01232 expression is upregulated in PAAD serum and tissue samples with considerable diagnostic and prognostic significance. In addition, miR-204-5p, miR-370-5p and miR-654-3p may be sponged by LINC01232 in PAAD, which also show potencies in PAAD diagnosis and prognosis.

Development and Validation of the Trans-Omics Model for Pancreatic Adenocarcinoma

Aim: To develop a trans-omics-based molecular clinicopathological algorithm for predicting pancreatic adenocarcinoma prognosis, we performed a comprehensive analysis of the expression levels of mRNA, DNA methylation and DNA copy number in The Cancer Genome Atlas dataset. Materials & methods: Based on the least absolute shrinkage and selection operator method - COX regression analysis, a trans-omics-based classifier was established to predict overall survival. Nomogram was constructed by combining the classifier band clinical pathological characterization. Results: Based on trans-omics, we developed a 10-gene-based classifier and a molecular-clinicopathologic nomogram for predicting overall survival with satisfactory accuracy. Conclusion: Trans-omics-based classifier and molecule-clinicopathological nomogram based on the classifier can accurately predict the prognosis of pancreatic adenocarcinoma patients.

Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer

BackgroundNeoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT. MethodsBetween 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses. ResultsThe postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively). ConclusionsCY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.

Abstract B110: Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year?

Abstract Purpose: Population-based studies indicated that prognosis of pancreatic adenocarcinoma (PAC) is worse in black patients compared to other races. Nonetheless, survival probabilities can change over time based on number of years (yr.) already survived by patients; a concept called conditional survival. This study explored the dynamic changes in risk according to patient characteristics, particularly race, on survival of PAC patients using cancer-specific survival (CSS) estimates. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for data on adult patients with non-metastatic PAC, diagnosed between 1988 and 2010. Patient characteristics, such as age, race, tumor grade, and stage were collected at the time of diagnosis. CSS probabilities, as well as Cox proportional hazard ratios (HRs), were computed at the time of diagnosis (Actuarial CSS and baseline HR), and after already surviving 1 to 6 yr. after diagnosis (Conditional CSS and HR). Harrell’s concordance index (C-index) was used to measure the cross-validation accuracy of the Cox models. Results: Our search retrieved data on 20,491 patients, with a mean age at diagnosis of 67.2 yr. Most of the patients were White (81.6%), followed by Black (12%) and Asians/Pacific Islander (6.4%). The stage was T1-2N0M0 in 15.9%, T3-4N0M0 in 41.8%, and T1-4N1M0 in 42.3% of patients. The 3-yr actuarial CSS calculated from time of diagnosis was significantly different across racial groups, at 11%, 10%, and 13% for Whites, Blacks, and Asians, respectively (P &amp;lt; 0.01). Conversely, for patients who already survived 1 yr. after diagnosis, the probability of surviving an additional 2 yr. was similar across races, at 26.2%, 27.1%, and 29.9%, for Whites, Blacks, and Asians, respectively (P = 0.218). As patients survived for longer periods of time following diagnosis, conditional CSS estimates increased similarly across different races; for White, Black, and Asian patients who already survived 3 yr. after diagnosis, the probability of surviving an additional 2 yr. was 62.6%, 60.5%, and 62.1%, respectively (P = 0.532). In multivariate cox models, the prognostic effect of race lost significance if patients already survived ≥1 yr. after diagnosis (Baseline HR = 1.114, 95%CI [1.045- 1.187], mean C-index = 67%; conditional HR at 1 yr = 1.015, 95%CI [0.919- 1.12], mean C-index = 60%). The prognostic effect of tumor grade, site, and age lost significance if patients already survived ≥2, ≥4, and ≥6 yr. after diagnosis, respectively. Tumor stage maintained its prognostic significance over time (conditional HR at 6 yr = 1.522, 95%CI [1.049- 2.208], mean C-index = 59%). Conclusion: Racial disparities in survival outcomes exist at the time of diagnosis for PAC patients. However, the survival impact of these disparities does not seem to persist over time. Other variables, such as age, tumor grade, stage, and treatment received should be taken into account when predicting future prognosis of PAC patients who have already survived ≥ 1 yr. after diagnosis. Citation Format: Anas M Saad, Maha AT Elsebaie, Mohamed Amgad, Muneer J Al-Husseini, Kyrillus S Shohdy, Omar Abdel-Rahman. Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B110.

The diversity between curatively resected pancreatic head and body-tail cancers based on the 8th edition of AJCC staging system: a multicenter cohort study

BackgroundTo our knowledge, there are no studies to systematically compare the detailed clinical significance between curatively resected pancreatic head (ph) and body-tail (pbt) ductal adenocarcinoma based on the new 8th edition of AJCC staging system (8th AJCC stage) that was just applied in clinical practice in 2018.MethodsThree hundred fifty-one patients with curatively resected pancreatic adenocarcinoma (PC) from three center hospitals were entered into this multicenter cohort study.ResultsIncreasing tumor size (P < 0.001), T stage (T1 + T2 vs T3 + T4, P = 0.003), frequent postoperative liver metastasis (PLM) (P = 0.002) and 8th AJCC stage (IA to VI, P < 0.001; I + II vs III + IV, P = 0.002) were closely associated with the progression of pbt cancers compared with that in ph cancer patients. Moreover, tumor size≥3 cm (P = 0.012), 8th AJCC stage (III + IV) (P = 0.025) and PLM (P = 0.010) were identified as independent risk factors in pbt cancers in logistic analysis. Patients with pbt cancers had a significantly worse overall survival compared with ph cancer patients (P = 0.003). Moreover, pbt was an independent unfavorable factor in multivariate analysis (P = 0.011). In addition to lymph nodes metastasis, 8th AJCC stage, vascular invasion and PLM, increasing tumor size and advanced T stage were also closely associated with the poor prognosis in 131 cases of pbt cancer patients compared with Ph cancer patients.ConclusionPbt, as an independent unfavorable factor for the prognosis of PC patients, are much more aggressive than that in ph cancers according to 8th AJCC staging system. 8th AJCC staging system are more comprehensive and sensitive to reflect the malignant biology of pbt cancers.

A 6‑gene risk score system constructed for predicting the clinical prognosis of pancreatic adenocarcinoma patients.

Pancreatic adenocarcinoma (PAC) is the most common type of pancreatic cancer, which commonly has an unfavorable prognosis. The present study aimed to develop a novel prognostic prediction strategy for PAC patients. mRNA sequencing data of PAC (the training dataset) were extracted from The Cancer Genome Atlas database, and the validation datasets (GSE62452 and GSE79668) were acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between good and poor prognosis groups were analyzed by limma package, and then prognosis-associated genes were screened using Cox regression analysis. Subsequently, the risk score system was constructed and confirmed using Kaplan-Meier (KM) survival analysis. After the survival associated-clinical factors were screened using Cox regression analysis, they were performed with stratified analysis. Using DAVID tool, the DEGs correlated with risk scores were conducted with enrichment analysis. The results revealed that there were a total of 242 DEGs between the poor and good prognosis groups. Afterwards, a risk score system was constructed based on 6 prognosis-associated genes (CXCL11, FSTL4, SEZ6L, SPRR1B, SSTR2 and TINAG), which was confirmed in both the training and validation datasets. Cox regression analysis showed that risk score, targeted molecular therapy, and new tumor (the new tumor event days after the initial treatment according to the TCGA database) were significantly related to clinical prognosis. Under the same clinical condition, 6 clinical factors (age, history of chronic pancreatitis, alcohol consumption, radiation therapy, targeted molecular therapy and new tumor (event days) had significant associations with clinical prognosis. Under the same risk condition, only targeted molecular therapy was significantly correlated with clinical prognosis. In conclusion, the 6-gene risk score system may be a promising strategy for predicting the outcome of PAC patients.

LncRNA SNHG8 promotes the development and chemo-resistance of pancreatic adenocarcinoma.

The aim of this study was to investigate the role of small nucleolar RNA host gene 8 (SNHG8) in the pathogenesis of pancreatic adenocarcinoma and to explore the possible underlying mechanism. SNHG8 expression in 40 pairs of pancreatic adenocarcinoma tissues and para-cancerous tissues, as well as 10 normal pancreas tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Survival analysis was conducted to explore the correlation between SNHG8 expression and the prognosis of pancreatic adenocarcinoma patients. After the transfection of SNHG8 siRNA into pancreatic adenocarcinoma cells, the proliferation and cell cycle were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Meanwhile, cell apoptosis was detected by flow cytometry and Western blot. The regulatory effect of SNHG8 on the chemo-sensitivity of pancreatic adenocarcinoma cells was assessed by CCK-8 assay. The expression of SNHG8 in pancreatic adenocarcinoma tissues was significantly higher than that of para-cancerous tissues and normal pancreatic tissues. Pancreatic adenocarcinoma patients with higher expression of SHNG8 presented shorter overall survival than those with lower expression. Meanwhile, SNHG8 expression was correlated with tumor stage and differentiation level, whereas not correlated with age, sex, tumor location and lymph node metastasis of pancreatic adenocarcinoma patients. In vitro results showed that SNHG8 knockdown significantly decreased the proliferative ability, prolonged G0/G1 phase and increased the apoptosis of Hs766T and PANC-1 cells. Western blot results elucidated that SNHG8 knockdown remarkably downregulated the protein expression levels of cleaved caspase-3 and cleaved PARP in Hs766T and PANC-1 cells. In addition, SNHG8 significantly decreased the chemo-sensitivity of pancreatic adenocarcinoma cells. SNHG8 is highly expressed in pancreatic adenocarcinoma tissues and is negatively correlated with its prognosis. Moreover, SNHG8 promotes cell proliferation and cell cycle, whereas inhibits cell apoptosis and reduces the chemo-sensitivity of pancreatic adenocarcinoma cells.

Pathology of pancreatic tumors

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the pancreas. It is an aggressive cancer that leads to rapid progression, high disease stage at presentation and diagnosis and therefore complicate treatment approaches. It has a peak incidence in the 7 th to 8 th decades of life and most are high stage at diagnosis and not surgically resectable. PDA is associated with multiple risk factors including environmental, dietary, chronic diseases and genetic. KRAS has been the most frequently altered oncogene in PDA (somatic KRAS mutations are present in >90% of cancers), clearly indicating that this gene is a driver of tumorigenesis in the pancreas. Frequently altered tumor suppressor genes have also been identified in PDA, including p16/CDKN2A, TP53, and SMAD4/DPC4, and these genes also represent drivers in pancreatic tumorigenesis. ROR2 plays an essential role as a prognostic marker of survival in patients with PDA and could be considered a potential therapeutic target in the future. Positive Nectin-2 and DDX3 expression were associated with the progression and poorer prognosis in pancreatic adenocarcinoma patients. Advancement in cancer genetics have improved the understanding of the disease and serve as screening and also prognostic markers. Here we review the pathology of PDA and other pancreatic tumors.