EZH2 G553C significantly increases the risk of brain metastasis from lung cancer due to salt bridge instability.

BACKGROUND: The incidence and mortality of lung cancer is the highest in China and the world. Brain is the most common distant metastasis site of lung cancer. Its transfer mechanism and predictive biomarkers are still unclear. EZH2 participates in the catalysis of transcriptional inhibition complex, mediates chromatin compactness, leads to the silencing of its downstream target genes, participates in the silencing of multiple tumor suppressor genes, and is related to cell proliferation, apoptosis and cycle regulation. In physiology, EZH2 has high activity in stem cells or progenitor cells, inhibits genes related to cell cycle arrest and promotes self-renewal. To detect the expression and mutation of EZH2 gene in patients with brain metastasis of lung cancer, and provide further theoretical basis for exploring the pathogenesis of brain metastasis of lung cancer and finding reliable biomarkers to predict brain metastasis of lung cancer. METHODS: This study investigated susceptible genes for brain metastasis of lung cancer. The second-generation sequencing technology was applied to screen the differential genes of paired samples (brain metastasis tissues, lung cancer tissues and adjacent tissues) of lung cancer patients with brain metastasi. RESULTS: It revealed that there was a significant difference in the G553C genotype of EZH2 between lung cancer brain metastasis tissues and lung cancer tissues (p = 0.045). The risk of lung cancer brain metastasis in G allele carriers was 2.124 times higher than that in C allele carriers. Immunohistochemistry showed that compared with lung cancer patients and lung cancer patients with brain metastasis, the expression level of EZH2 in lung cancer tissues of lung cancer patients was significantly higher than that in adjacent lung tissues (p < 0.0001), and higher than that in brain metastasis tissues (p = 0.0309). RNA in situ immunohybridization showed that EZH2 mRNA expression was gradually high in lung cancer adjacent tissues, lung cancer tissues and lung cancer brain metastasis tissues. CONCLUSIONS: EZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis.

High-Speed and Accurate Diagnosis of Gastrointestinal Disease: Learning on Endoscopy Images Using Lightweight Transformer with Local Feature Attention.

In response to the pressing need for robust disease diagnosis from gastrointestinal tract (GIT) endoscopic images, we proposed FLATer, a fast, lightweight, and highly accurate transformer-based model. FLATer consists of a residual block, a vision transformer module, and a spatial attention block, which concurrently focuses on local features and global attention. It can leverage the capabilities of both convolutional neural networks (CNNs) and vision transformers (ViT). We decomposed the classification of endoscopic images into two subtasks: a binary classification to discern between normal and pathological images and a further multi-class classification to categorize images into specific diseases, namely ulcerative colitis, polyps, and esophagitis. FLATer has exhibited exceptional prowess in these tasks, achieving 96.4% accuracy in binary classification and 99.7% accuracy in ternary classification, surpassing most existing models. Notably, FLATer could maintain impressive performance when trained from scratch, underscoring its robustness. In addition to the high precision, FLATer boasted remarkable efficiency, reaching a notable throughput of 16.4k images per second, which positions FLATer as a compelling candidate for rapid disease identification in clinical practice.

An Actinic Keratosis Auxiliary Diagnosis Method Based on an Enhanced MobileNet Model.

Actinic keratosis (AK) is a common precancerous skin lesion with significant harm, and it is often confused with non-actinic keratoses (NAK). At present, the diagnosis of AK mainly depends on clinical experience and histopathology. Due to the high difficulty of diagnosis and easy confusion with other diseases, this article aims to develop a convolutional neural network that can efficiently, accurately, and automatically diagnose AK. This article improves the MobileNet model and uses the AK and NAK images in the HAM10000 dataset for training and testing after data preprocessing, and we performed external independent testing using a separate dataset to validate our preprocessing approach and to demonstrate the performance and generalization capability of our model. It further compares common deep learning models in the field of skin diseases (including the original MobileNet, ResNet, GoogleNet, EfficientNet, and Xception). The results show that the improved MobileNet has achieved 0.9265 in accuracy and 0.97 in Area Under the ROC Curve (AUC), which is the best among the comparison models. At the same time, it has the shortest training time, and the total time of five-fold cross-validation on local devices only takes 821.7 s. Local experiments show that the method proposed in this article has high accuracy and stability in diagnosing AK. Our method will help doctors diagnose AK more efficiently and accurately, allowing patients to receive timely diagnosis and treatment.

Immune disguise: the mechanisms of Neu5Gc inducing autoimmune and transplant rejection.

Organ (stem cell) transplantation is the most effective treatment for advanced organ failure. Neu5Gc (N-hydroxyacetylneuraminic acid) is a pathogenic non-human sialic acid, which is very similar to the molecular structure of Neu5Ac (N-acetylneuraminic acid) in human body. Neu5Gc has the function of "immune disguise", which is the main obstacle to transplantation. Gene knockout such as cytidine monophosphate-N-acetylneuraminidase (CMAH) reduces donor antigenicity, making xenotransplantation from fiction to reality. Exploring the immune disguise event in this emerging field has become a hot topic in the research of transplantation immune tolerance mechanism.

Trypsin may induce cytokine storm in M1 macrophages, resulting in critical coronavirus disease.

Trypsin is a protease-activated receptor-2 (PAR2) activator that upregulates the interleukin (IL)-17 receptor signal in the airway epithelial cells and amplifies the inflammatory response, but does not modify the growth kinetics of the metapneumovirus. How does the coronavirus spread from cell to cell is yet an enigma. The present study analyzed the possible role of trypsin in the activation of coronavirus in vitro and in vivo. We found that the overexpression of trypsin in A549 cells upregulated IL-17 and angiotensin-converting enzyme (ACE). In the humanized transgenic mice, trypsin activated M1 macrophages. Together, our results suggested that the upregulation of trypsin may support a new pathway for coronavirus transmission in patients.

Molecular Diversity of Peptide Toxins in the Venom of Spider Heteropoda pingtungensis as Revealed by cDNA Library and Transcriptome Sequencing Analysis.

The venoms of toxic animals are chemical pools composed of various proteins, peptides, and small organic molecules used for predation and defense, in which the peptidic toxins have been intensively pursued mining modulators targeting disease-related ion channels and receptors as valuable drug pioneers. In the present study, we uncovered the molecular diversity of peptide toxins in the venom of the spider Heteropoda pingtungensis (H. pingtungensis) by using a combinatory strategy of venom gland cDNA library and transcriptome sequencing (RNA-seq). An amount of 991 high-quality expressed sequence tags (ESTs) were identified from 1138 generated sequences, which fall into three categories, such as the toxin-like ESTs (531, 53.58%), the cellular component ESTs (255, 25.73%), and the no-match ESTs (205, 20.69%), as determined by gene function annotations. Of them, 190 non-redundant toxin-like peptides were identified and can be artificially grouped into 13 families based on their sequence homology and cysteine frameworks (families A-M). The predicted mature toxins contain 2-10 cysteines, which are predicted to form intramolecular disulfide bonds to stabilize their three-dimensional structures. Bioinformatics analysis showed that toxins from H. pingtungensis venom have high sequences variability and the biological targets for most toxins are unpredictable due to lack of homology to toxins with known functions in the database. Furthermore, RP-HPLC and MALDI-TOF analyses have identified a total of 110 different peptides physically existing in the H. pingtungensis venom, and many RP-HPLC fractions showed potent inhibitory activity on the heterologously expressed NaV1.7 channel. Most importantly, two novel NaV1.7 peptide antagonists, µ-Sparatoxin-Hp1 and µ-Sparatoxin-Hp2, were characterized. In conclusion, the present study has added many new members to the spider toxin superfamily and built the foundation for identifying novel modulators targeting ion channels in the H. pingtungensis venom.

CGRP: A New Endogenous Cell Stemness Maintenance Molecule.

Stem cells have the ability of self-replication and multidirectional differentiation, but the mechanism of how stem cells "maintain" this ability and how to "decide" to give up this state and differentiate into cells with specific functions is still unknown. The Nobel Prize in physiology and medicine in 2021 was awarded to "temperature and tactile receptor," which made the pain receptor TRPV1-calcitonin gene-related peptide (CGRP) pathway active again. The activation and blocking technology of CGRP has been applied to many clinical diseases. CGRP gene has complex structure and transcription process, with multiple methylation and other modification sites. It has been considered as a research hotspot and difficulty since its discovery. Drug manipulation of TRPV1 and inhibition of CGRP might improve metabolism and prolong longevity. However, whether the TRPV1-neuropeptide-CGRP pathway is directly or indirectly involved in stem cell self-replication and multidirectional differentiation is unclear. Recent studies have found that CGRP is closely related to the migration and differentiation of tumor stem cells, which may be realized by turning off or turning on the CGRP gene expression in stem cells and activating a variety of ways to regulate stem cell niches. In this study, we reviewed the advances in researches concentrated on the biological effects of CGRP as a new endogenous switching of cell stemness.

Synthesis, biological evaluation, pharmacokinetic studies and molecular docking of 4'''-acetyl-delicaflavone as antitumor agents.

Structural modification of natural products is the effective option to improve their pharmacological effects and drug properties. DLF is a lead compound of antitumor drug, which is a broad-spectrum, low toxic and high-efficient component isolated from Selaginella doederleinii Hieron by our research group. Here, we report the structural modification method of this component, and find that the acetylated product of C4'''- OH (C4'''-acetyl-delicaflavone, 4'''ADLF) has better inhibitory effect on the selected cancer cell lines, including, lung, liver, colon and cervical cancer cell lines. Since the increased water solubility of 4'''ADLF may lead to higher absorption rate and activity, we evaluate the pharmacodynamics in vitro and in vivo, and the pharmacokinetic of 4'''ADLF. It shows that 4'''ADLF inhibit the proliferation and induce cycle arrest in tumor cells, and had better anticancer activity and bioavailability than DLF.

Exosomal LBH inhibits epithelial-mesenchymal transition and angiogenesis in nasopharyngeal carcinoma via downregulating VEGFA signaling.

The limb-bud and heart (LBH) gene was reported to suppress nasopharyngeal carcinoma (NPC) progression in our previous study. Distant metastasis predominantly accounts for the unsatisfactory prognosis of NPC treatment, in which epithelial-mesenchymal transition (EMT) and tumor angiogenesis are of great significance. The roles of exosomes in mediating NPC progression have been highlighted in recent researches, and attempts have been made to explore the clinical application of NPC exosomes. Here we investigated the function of the LBH gene in NPC exosomes, and its potential mechanism. NPC xenografts were constructed, showing that vascular endothelial growth factor A (VEGFA) expression and neovascularity were attenuated by LBH overexpression, together with diminished EMT progression. NPC-derived exosomes were isolated, identified and applied for in vitro/in vivo experiments, and the exosomal distribution of LBH was elevated in exosomes derived from LBH-upregulated cells. Ectopic LBH, αB-crystallin (CRYAB) and VEGFA expression was induced by lentiviral infection or plasmid transfection to explore their functions in modulating EMT and angiogenesis in NPC. The addition of LBH+ NPC exosomes during a Matrigel plug assay in mice suppressed in vivo angiogenesis, and the treatment of human umbilical vein endothelial cells (HUVECs) with LBH+ NPC exosomes inhibited cellular proliferation, migration and tube formation. The interactions among LBH, CRYAB and VEGFA were confirmed by colocalization and fluorescence resonance energy transfer (FRET) assays, and extracellular VEGFA secretion from both HUVECs and NPC cells under the treatment with LBH+ NPC exosomes was diminished according to ELISA results. We concluded that exosomal LBH inhibits EMT progression and angiogenesis in the NPC microenvironment, and that its effects are partially implemented by modulation of VEGFA expression, secretion and related signaling. Thus, LBH could serve as a promising therapeutic target in VEGFA-focused NPC treatment.

Methylation of CALCA and CALCB in Pancreatic Ductal Adenocarcinoma.

Calcitonin gene-related peptide (CGRP) plays a diverse and intricate role in chronic low-grade inflammation and is closely related to specific cancers. It includes two subtypes, CALCA (αCGRP) and CALCB (ßCGRP), of which αCGRP expression accounts for more than 90%. Here, we show that methylation of CALCA and CALCB in pancreatic ductal adenocarcinoma was significantly higher than that in paracancer. Western blot and immunohistochemistry showed that CGRP, p-AKT, and p-CREB in the tumor tissues were lower than those in the paracarcinoma tissues. In vivo, the expressions of p-AKT and p-CREB in the pancreatic tissues of CALCA-KO rats were also lower than those of wild type. Methylation of CALCA and CALCB is increased in pancreatic adenocarcinoma, and under that condition, p-AKT and p-CREB levels were decreased.

Pancreatic cancer: A review of epidemiology, trend, and risk factors.

Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.

CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland.

OBJECTIVES: To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (ßCGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma. MATERIALS AND METHODS: Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum calcitonin gene-related peptide (CGRP) and its concentration of alpha and beta subtypes. RESULTS: Univariate logistic regression analysis showed that the CALCB rs2839222 T/T genotype was closely related to the occurrence of salivary adenoid cystic carcinoma, with a correlation coefficient of 3.89. CONCLUSIONS: The serum CGRP concentration in the salivary adenoid cystic carcinoma group was 1.56 times that of the normal control group. The αCGRP subtype was significant, which was 3.02 times that of the normal control. The polymorphism of ßCGRP gene is associated with genetic susceptibility to salivary adenoid cystic carcinoma, and serum CGRP and ßCGRP can be used as novel markers of salivary adenoid cystic carcinoma.

DDIT4 Novel Mutations in Pancreatic Cancer.

Pancreatic cancer is one of the most common malignancies worldwide. This study is aimed at searching the possible genetic mutations and the value of novel gene mutation in the DNA damage-inducible transcript 4 (DDIT4) and signaling pathway in pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the DNA sequences of DDIT4 from patients with pancreatic ductal adenocarcinoma. In addition, we used IHC to detect the expression level of DDIT4 in patients with pancreatic cancer in different types of gene mutation. Double-labeled immunofluorescence was employed to explore the expression levels of DDIT4/LC3 and their potential correlation. Our work indicated the two novel stable gene mutations in DDIT4 mRNA 3'-untranslated region (m.990 U>A and m.1246 C>U). Thirteen samples were found to have mutation in the DDIT4 3'-untranslated regions (UTR). To further verify the influence of gene mutation on protein expression, we performed immunohistochemistry on different gene mutation types, and we found a correlation between DDIT4 expression and gene mutation, which is accompanied by nuclear staining deepening. In order to further discuss the clinical value of DDIT4 gene mutation, immunofluorescence suggested that the expression of DDIT4 colocated with LC3; thus, we speculated that DDIT4 mutation may be involved in autophagy in pancreatic cancer cell. In this study, we found mutation in the 3'-UTR region of DDIT4, which may be associated with DDIT4 expression and tumor autophagy in pancreatic cancer tissues.

Limb-bud and heart (LBH) inhibits cellular migration, invasion and epithelial-mesenchymal transition in nasopharyngeal carcinoma via downregulating αB-crystallin expression.

Limb-bud and heart (LBH) gene has received increasing attention in recent cancer studies. Here we investigated the role of the LBH gene in regulating the metastasis capacity and epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC) cells, and its potential mechanism. The expressions of LBH and αB-crystallin (CRYAB) were modulated by lentiviral infection, or plasmid/siRNA transfection, and the phosphorylation of p38 was suppressed by an inhibitor, to explore their functions in modulating NPC cell phenotypes, as well as the relationships of these factors with each other. Cellular proliferation, migration and invasion were examined by RTCA system, Transwell assays and Matrigel Transwell assays respectively. The EMT progression was indicated by RT-qPCR and Western blotting measuring the expressions of EMT biomarkers. NPC xenografts were constrcucted, and formed tumors were sectioned for morphology and immunohistofluorescence. The interaction between LBH and CRYAB was examined by colocalization and Fluorescence resonance energy transfer (FRET) analysis. We reached the conclusion that LBH inhibits the proliferation, migration, invasion and EMT of NPC cells, and its effects were partially achieved by suppressing p38 phosphorylation, which subsequently downregulates the mRNA expression and phosphorylation of CRYAB, while CRYAB directly interacts with LBH in NPC cells. This LBH-related pathway we revealed provides a novel therapeutic target for nasopharyngeal carcinoma research.

Upregulated lnc-HZ02 and miR-hz02 inhibited migration and invasion by downregulating the FAK/SRC/PI3K/AKT pathway in BPDE-treated trophoblast cells.

BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), a metabolite of environmental carcinogenic BaP, weakens the migration and invasion of human villous trophoblast cells and may further induce miscarriage. However, the underlying mechanisms remain largely unknown. In this study, we identified that in trophoblast Swan 71 and HTR-8/SVneo cells, miR-hz02 upregulates the level of lnc-HZ02, which inhibits the expression of an RNA-binding protein HuR. HuR could interact with FAK mRNA and promote its mRNA stability, thus upregulating the FAK level and the FAK/SRC/PI3K/AKT pathway, and finally maintaining the normal migration and invasion of trophoblast cells. If trophoblast cells are exposed to BPDE, both miR-hz02 and lnc-HZ02 are upregulated, which reduce the level of HuR, weaken the interactions of HuR with FAK mRNA, downregulate FAK level and the FAK/SRC/PI3K/AKT pathway, and finally inhibit cell migration and invasion. This study provides a novel scientific understanding of the dysfunctions of human trophoblast cells.

A review of the mechanism of DDIT4 serve as a mitochondrial related protein in tumor regulation.

DDIT4 is a mitochondrial and tumor-related protein involved in anti-tumor therapy resistance, proliferation, and invasion, etc. Its expression level increases under the stress such as chemotherapy, hypoxia, and DNA damage. A number of clinical studies have confirmed that DDIT4 can change the behavior of tumor cells and the prognosis of patients with cancer. However, the role of DDIT4 in promoting or suppressing cancer is still inconclusive. This article summarized the four characteristics of DDIT4 including a mitochondria-related protein, interactions with various protein molecules, immune and metabolic cell related proteins and participator in the oxygen sensing pathway, which may be related to the progress of cancer.

Effects of Environmental Endocrine-Disrupting Chemicals on Female Reproductive Health.

Environmental endocrine-disrupting chemicals (EDCs) are xenobiotic compounds that are frequently contacted in daily life. With the species and quantity of substances created and utilized by human beings significantly surpassing the self-purification capacity of nature, a large number of hazardous substances are enriched in the human body through the respiratory tract, digestive tract, and skin. Some of these compounds cause many problems endangering female reproductive health by simulating/antagonizing endogenous hormones or affecting the synthesis, metabolism, and bioavailability of endogenous hormones, including reproductive disorders, fetal birth defects, fetal developmental abnormalities, endocrine and metabolic disorders, and even gynecological malignancies. Therefore, the study of the relationship between environmental EDCs and female reproductive diseases and related mechanisms is of considerable significance to women, children health care, and improve the quality of the population.

JMJD2C triggers the growth of multiple myeloma cells via activation of ß­catenin.

Emerging evidence has indicated that histone modification and its related regulators are involved in the progression of multiple myeloma (MM) cells. In the present study, the expression of Jumonji C domain­containing 2 (JMJD2) was examined in both MM tissues and healthy controls. The roles of JMJD2C in the progression of MM were further investigated. The results revealed that the expression of JMJD2C, but not that of JMJD2A or JMJD2B, was increased in MM tissues compared with the healthy controls. The overexpression of JMJD2C significantly increased the in vitro growth of MM cells. The inhibitor of the ß­catenin signaling pathway significantly attenuated the JMJD2C­induced growth of MM cells. Mechanistical analyses indicated that JMJD2C increased the transcription of ß­catenin in MM cells, which may be due to the fact that JMJD2C can directly bind with the promoter of ß­catenin. Furthermore, JMJD2C activated ß­catenin in MM cells via a GSK3ß­dependent manner, which was evidenced by the results demonstrating that the overexpression of GSK3ß attenuated the JMJD2C­induced decrease in the phosphorylation of ß­catenin. On the whole, the findings of the present study demonstrated that JMJD2C promotes the malignancy of MM via the activation of the ß­catenin pathway. These results suggested that JMJD2C may be a potential target for MM treatment.

Improved solubility, dissolution rate, and oral bioavailability of main biflavonoids from Selaginella doederleinii extract by amorphous solid dispersion.

Amentoflavone, robustaflavone, 2″,3″-dihydro-3',3‴-biapigenin, 3',3‴-binaringenin, and delicaflavone are five major hydrophobic components in the total biflavonoids extract from Selaginella doederleinii (TBESD) that display favorable anticancer properties. The purpose of this study was to develop a new oral delivery formulation to improve the solubilities, dissolution rates, and oral bioavailabilities of the main ingredients in TBESD by the solid dispersion technique. Solid dispersions of TBESD with various hydrophilic polymers were prepared, and different technologies were applied to select the suitable carrier and method. TBESD amorphous solid dispersion (TBESD-ASD) with polyvinylpyrrolidone K-30 was successfully prepared by the solvent evaporation method. The physicochemical properties of TBESD-ASD were investigated by scanning electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. As a result, TBESD was found to be molecularly dispersed in the amorphous carrier. The solubilities and dissolution rates of all five ingredients in the TBESD-ASD were significantly increased (nearly 100% release), compared with raw TBESD. Meanwhile, TBESD-ASD showed good preservation stability for 3 months under accelerated conditions of 40 °C and 75% relative humidity. A subsequent pharmacokinetic study in rats revealed that Cmax and AUC0-t of all five components were significantly increased by the solid dispersion preparation. An in vivo study clearly revealed that compared to raw TBESD, a significant reduction in tumor size and microvascular density occurred after oral administration of TBESD-ASD to xenograft-bearing tumor mice. Collectively, the developed TBESD-ASD with the improved solubility, dissolution rates and oral bio-availabilities of the main ingredients could be a promising chemotherapeutic agent for cancer treatment.

PRSS1 genotype is associated with prognosis in patients with pancreatic ductal adenocarcinoma.

The prognostic value of the genotype of the PRSS1 gene in patients with pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. The aim of the present study was to evaluate the association between the PRSS1 genotype and clinicopathological characteristics of patients with PDAC, as well as to explore the prognostic significance of the PRSS1 genotype in patients with PDAC. A total of 124 patients with PDAC patients were included in the current study and the PRSS1 genotype of the enrolled patients was determined by the polymerase chain reaction. Associations between the PRSS1 genotype and clinicopathological characteristics were subsequently analyzed using the Chi-square test. The impact of the PRSS1 genotype on patient prognosis was assessed using the Kaplan-Meier method, and predictive factors of overall survival (OS) time were analyzed by Cox regression. A total of 56 patients with PDAC (45.16%) had the T/C PRSS1 genotype, which was associated with large tumor sizes (P=0.027) and higher tumor node metastasis (TNM) stages (P=0.041). Following a median follow-up of 19 months, the T/C genotype of PRSS1 genotype was associated with a shorter OS time (P=0.037) compared with the C/C or T/T PRSS1 genotypes. Univariate and multivariate analyses revealed that PRSS1 genotype was identified to be an independent prognostic factor for the OS time of patients with PDAC. The results obtained in the current study suggested that the PRSS1 genotype, as well as factors such as the serum level of carbohydrate antigen 19-9 and the TNM stage, may act as independent prognostic factors for the OS time of patients with PDAC.