Recent Advances in Tactile Sensory Systems: Mechanisms, Fabrication, and Applications.

Flexible electronics is a cutting-edge field that has paved the way for artificial tactile systems that mimic biological functions of sensing mechanical stimuli. These systems have an immense potential to enhance human-machine interactions (HMIs). However, tactile sensing still faces formidable challenges in delivering precise and nuanced feedback, such as achieving a high sensitivity to emulate human touch, coping with environmental variability, and devising algorithms that can effectively interpret tactile data for meaningful interactions in diverse contexts. In this review, we summarize the recent advances of tactile sensory systems, such as piezoresistive, capacitive, piezoelectric, and triboelectric tactile sensors. We also review the state-of-the-art fabrication techniques for artificial tactile sensors. Next, we focus on the potential applications of HMIs, such as intelligent robotics, wearable devices, prosthetics, and medical healthcare. Finally, we conclude with the challenges and future development trends of tactile sensors.

The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3.

Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p-SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.

Solid pseudopapillary neoplasm (SPN) of the pancreas: current understanding on its malignant potential and management.

Solid pseudopapillary neoplasms (SPN) of the pancreas are presently recognized as low-grade malignant tumors that are frequently observed in young females. This tumor has a low incidence and is associated with an excellent prognosis following surgical resection. Typical SPNs primarily affect the pancreas and tend to have moderate or asymptomatic manifestations. Based on retrospective research, it is anticipated that patients with SPN can achieve disease-free survival, even in cases when metastasis is detected during inspection. However, the incidence of malignant SPN has been consistently underestimated, as evidenced by recent research findings. Malignancy of SPN primarily encompasses invasion and infiltration, metastasis, and recurrence after R0 resection. Imaging technologies such as Ultrasound, Computed Tomography, Magnetic Resonance Imaging, and Position Emission Tomography are capable of preliminarily identifying malignant SPN, which is primarily based on its invasive clinical features. Research on risk factors of malignant SPN revealed that larger tumor size, Ki-67 index, and several other parameters had significant correlations with invasive tumor behavior. Pathologic features of malignant SPNs overlay other pancreatic tumors, nevertheless they can provide valuable assistance in the process of diagnosis. Several confirmed specific pathologic biomarkers are related to its cellular origin, characteristic gene mutation, and cell proliferation. Considering the invasiveness of malignant SPN, it is imperative to enhance the comprehensiveness of its therapy. Tumor resection remains a suggested course of action in line with typical SPN, and additional lymph node dissection is seen as reasonable. Compared to benign SPNs, malignant SPNs have worse prognosis, underscoring the necessity of early identification and treatment in comprehensive medical centers to get improved clinical outcomes.

Ribosome profiling: a powerful tool in oncological research.

Neoplastic cells need to adapt their gene expression pattern to survive in an ever-changing or unfavorable tumor microenvironment. Protein synthesis (or mRNA translation), an essential part of gene expression, is dysregulated in cancer. The emergence of distinct translatomic technologies has revolutionized oncological studies to elucidate translational regulatory mechanisms. Ribosome profiling can provide adequate information on diverse aspects of translation by aiding in quantitatively analyzing the intensity of translating ribosome-protected fragments. Here, we review the primary currently used translatomics techniques and highlight their advantages and disadvantages as tools for translatomics studies. Subsequently, we clarified the areas in which ribosome profiling could be applied to better understand translational control. Finally, we summarized the latest advances in cancer studies using ribosome profiling to highlight the extensive application of this powerful and promising translatomic tool.

PFENet++: Boosting Few-Shot Semantic Segmentation With the Noise-Filtered Context-Aware Prior Mask.

In this work, we revisit the prior mask guidance proposed in "Prior Guided Feature Enrichment Network for Few-Shot Segmentation". The prior mask serves as an indicator that highlights the region of interests of unseen categories, and it is effective in achieving better performance on different frameworks of recent studies. However, the current method directly takes the maximum element-to-element correspondence between the query and support features to indicate the probability of belonging to the target class, thus the broader contextual information is seldom exploited during the prior mask generation. To address this issue, first, we propose the Context-aware Prior Mask (CAPM) that leverages additional nearby semantic cues for better locating the objects in query images. Second, since the maximum correlation value is vulnerable to noisy features, we take one step further by incorporating a lightweight Noise Suppression Module (NSM) to screen out the unnecessary responses, yielding high-quality masks for providing the prior knowledge. Both two contributions are experimentally shown to have substantial practical merit, and the new model named PFENet++ significantly outperforms the baseline PFENet as well as all other competitors on three challenging benchmarks PASCAL-5 i, COCO-20 i and FSS-1000. The new state-of-the-art performance is achieved without compromising the efficiency, manifesting the potential for being a new strong baseline in few-shot semantic segmentation.

Pancreatic ductal adenocarcinoma chemoresistance: From metabolism reprogramming to novel treatment.

ABSTRACT: As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

Development and validation of an interpretable Markov-embedded multilabel model for predicting risks of multiple postoperative complications among surgical inpatients: a multicenter prospective cohort study.

BACKGROUND: When they encounter various highly related postoperative complications, existing risk evaluation tools that focus on single or any complications are inadequate in clinical practice. This seriously hinders complication management because of the lack of a quantitative basis. An interpretable multilabel model framework that predicts multiple complications simultaneously is urgently needed. MATERIALS AND METHODS: The authors included 50 325 inpatients from a large multicenter cohort (2014-2017). The authors separated patients from one hospital for external validation and randomly split the remaining patients into training and internal validation sets. A MARKov-EmbeDded (MARKED) multilabel model was proposed, and three models were trained for comparison: binary relevance, a fully connected network (FULLNET), and a deep neural network. Performance was mainly evaluated using the area under the receiver operating characteristic curve (AUC). The authors interpreted the model using Shapley Additive Explanations. Complication-specific risk and risk source inference were provided at the individual level. RESULTS: There were 26 292, 6574, and 17 459 inpatients in the training, internal validation, and external validation sets, respectively. For the external validation set, MARKED achieved the highest average AUC (0.818, 95% CI: 0.771-0.864) across eight outcomes [compared with binary relevance, 0.799 (0.748-0.849), FULLNET, 0.806 (0.756-0.856), and deep neural network, 0.815 (0.765-0.866)]. Specifically, the AUCs of MARKED were above 0.9 for cardiac complications [0.927 (0.894-0.960)], neurological complications [0.905 (0.870-0.941)], and mortality [0.902 (0.867-0.937)]. Serum albumin, surgical specialties, emergency case, American Society of Anesthesiologists score, age, and sex were the six most important preoperative variables. The interaction between complications contributed more than the preoperative variables, and formed a hierarchical chain of risk factors, mild complications, and severe complications. CONCLUSION: The authors demonstrated the advantage of MARKED in terms of performance and interpretability. The authors expect that the identification of high-risk patients and the inference of the risk source for specific complications will be valuable for clinical decision-making.

Regulatory role of RNA modifications in the treatment of pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) is an extremely life-threatening malignancy with a relatively unfavorable prognosis. The early occurrence of metastasis and local recurrence subsequent to surgery contribute to the poor survival rates of PDAC patients, thereby limiting the effectiveness of surgical intervention. Additionally, the desmoplastic and immune-suppressive tumor microenvironment of PDAC diminishes its responsiveness to conventional treatment modalities such as chemotherapy, radiotherapy, and immunotherapy. Therefore, it is imperative to identify novel therapeutic targets for PDAC treatment. Chemical modifications are prevalent in various types of RNA and exert significant influence on their structure and functions. RNA modifications, exemplified by m6A, m5C, m1A, and Ψ, have been identified as general regulators of cellular functions. The abundance of specific modifications, such as m6A, has been correlated with cell proliferation, invasion, migration, and patient prognosis in PDAC. Pre-clinical data has indicated that manipulating RNA modification regulators could enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. Therefore, targeting RNA modifications in conjunction with current adjuvant or neoadjuvant therapy holds promise. The objective of this review is to provide a comprehensive overview of RNA modifications in PDAC treatment, encompassing their behaviors, mechanisms, and potential treatment targets. Therefore, it aims to stimulate the development of novel therapeutic approaches and future clinical trials.

Epidemiology of pancreatic cancer: New version, new vision.

Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies. This comprehensive review aims to provide a thorough analysis of the epidemiology of PC, discussing its incidence, risk factors, screening strategies and socioeconomic burden. We compiled a wide range of seminal studies as well as epidemiological investigations to serve this review as a comprehensive guide for researchers, healthcare professionals, and policymakers keen for a more profound understanding of PC epidemiology. This review highlights the essentiality of persistent research efforts, interdisciplinary collaboration, and public health initiatives to address the expanding burden of this malignancy.

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm.

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.

Novel strategies optimize immunotherapy by improving the cytotoxic function of T cells for pancreatic cancer treatment.

Pancreatic cancer (PC) is considered highly malignant due to its unsatisfying prognosis and limited response to therapies. Immunotherapy has therefore been developed to harness the antigen-specific properties and cytotoxicity of the immune system, aiming to induce a robust anti-tumor immune response that specifically demolishes PC cells while minimizing lethality in healthy tissue. The activation and augmentation of cytotoxic T cells play a critical role in the initiation and final success of immunotherapy. PC, however, is often immunotherapy resistant due to its intrinsic immunosuppressive tumor microenvironment that consequently hampers effective T cell priming. Emerging therapeutic approaches are orientated to modulate the tumor microenvironment in PC to enhance immune system involvement and heighten T cell efficacy. These novel strategies have shown promising therapeutic effects in the treatment of PC either as standalone approaches or combinatorial with other therapeutic schemes. The objective of this article is to explore innovative approaches to optimize immunotherapy for PC patients through T cell cytotoxic function augmentation.

Local resection for solid pseudopapillary neoplasms of the pancreas shows improved postoperative gastrointestinal function and reduced mental stress: a multiquestionnaire survey from a large cohort.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant pancreatic tumor with a highly favorable prognosis. Most SPN patients are young and middle-aged women. The main controversial topic for SPN is local resection (LR) versus radical resection (RR). Theoretically, LR could lead to better gastrointestinal function (GIF) and less mental stress. However, no data is available to support this hypothesis. METHODS: All SPN patients undergoing surgical treatment in Peking Union Medical College Hospital from 2001 to 2021 were included in the study. A cross-sectional online multiquestionnaire survey containing 110 questions was sent to them (Clinicaltrial.org, NCT05604716). This online multiquestionnaire survey focused on GIF and mental stress and consisted of eight questionnaires. Multiple linear regression analysis was conducted to identify independent factors impacting GIF and mental stress. RESULTS: A total of 183 cases provided valid results. Among them, 46 patients (25.1%) underwent LR, and 137 (74.9%) underwent RR. Ninety-four cases (51.4%) underwent minimally invasive surgery (MIS), while 89 (48.6%) underwent open surgery. The average GSRS score of the patients was 1.9±0.7, indicating that most suffered from mild gastrointestinal dysfunction. The scores of PHQ-9 and GAD-7 in 16 patients (8.7%) and 27 (14.8%) patients, respectively, were beyond 10.0, which indicated clinical depression and anxiety. Additionally, 19 (10.4%) patients reported poor ability to work, and 31(16.9%) patients had significant body image concerns. Compared to other clinicopathological characteristics, LR (LR vs. RR: PHQ-9 score, P =0.018; WAI average score, P =0.010; EORTC QLQ-C30, nine subdomains, P <0.05; GSRS average score, P =0.006) and MIS (MIS vs. open surgery: EORTC QLQ-C30, three subdomains, P <0.05; GSRS average score, P =0.006) were the most significant factors predicting improved GIF and reduced mental stress. CONCLUSIONS: This study systematically presents postoperative GIF and mental stress of SPN patients using validated multiquestionnaires for the first time. It provides solid evidence that LR and MIS can improve GIF and reduce mental stress after surgery for SPN patients, which could be helpful for the surgeons to make more personalized surgical plans for their patients.

From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.

PURPOSE: This study aims to review the multifaceted roles of a membrane protein named Fibroblast Activation Protein (FAP) expressed in tumor tissue, including its molecular functionalities, regulatory mechanisms governing its expression, prognostic significance, and its crucial role in cancer diagnosis and treatment. METHODS: Articles that have uncovered the regulatory role of FAP in tumor, as well as its potential utility within clinical realms, spanning diagnosis to therapeutic intervention has been screened for a comprehensive review. RESULTS: Our review reveals that FAP plays a pivotal role in solid tumor progression by undertaking a multitude of enzymatic and nonenzymatic roles within the tumor stroma. The exclusive presence of FAP within tumor tissues highlights its potential as a diagnostic marker and therapeutic target. The review also emphasizes the prognostic significance of FAP in predicting tumor progression and patient outcomes. Furthermore, the emerging strategies involving FAPI inhibitor (FAPI) in cancer research and clinical trials for PET/CT diagnosis are discussed. And targeted therapy utilizing FAP including FAPI, chimeric antigen receptor (CAR) T cell therapy, tumor vaccine, antibody-drug conjugates, bispecific T-cell engagers, FAP cleavable prodrugs, and drug delivery system are also introduced. CONCLUSION: FAP's intricate interactions with tumor cells and the tumor microenvironment make it a promising target for diagnosis and treatment. Promising strategies such as FAPI offer potential avenues for accurate tumor diagnosis, while multiple therapeutic strategies highlight the prospects of FAP targeting treatments which needs further clinical evaluation.

Organoid: Bridging the gap between basic research and clinical practice.

Nowadays, the diagnosis and treatment system of malignant tumors has increasingly tended to be more precise and personalized while the existing tumor models are still unable to fully meet the needs of clinical practice. Notably, the emerging organoid platform has been proven to have huge potential in the field of basic-translational medicine, which is expected to promote a paradigm shift in personalized medicine. Here, given the unique advantages of organoid platform, we mainly explore the prominent role of organoid models in basic research and clinical practice from perspectives of tumor biology, tumorigenic microbes-host interaction, clinical decision-making, and regenerative strategy. In addition, we also put forward some practical suggestions on how to construct a new generation of organoid platform, which is destined to vigorously promote the reform of basic-translational medicine.

Advanced progress on the significant influences of multi-dimensional nanofillers on the tribological performance of coatings.

Over the past two decades, nanofillers have attracted significant interest due to their proven chemical, mechanical, and tribological performances. However, despite the significant progress realized in the application of nanofiller-reinforced coatings in various prominent fields, such as aerospace, automobiles and biomedicine, the fundamental effects of nanofillers on the tribological properties of coatings and their underlying mechanisms have rarely been explored by subdividing them into different sizes ranging from zero-dimensional (0D) to three-dimensional (3D) architectures. Herein, we present a systematic review of the latest advances on multi-dimensional nanofillers for enhancing the friction reduction and wear resistance of metal/ceramic/polymer matrix composite coatings. Finally, we conclude with an outlook for future investigations on multi-dimensional nanofillers in tribology, providing possible solutions for the key challenges in their commercial applications.

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Objective: Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown. Methods: The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated. SiRNA and plasmids were applied to investigate the effects of PRKRA on PC cells. Organoids and cell lines with knockout and overexpression of PRKRA were established by CRISPR/Cas9 and lentivirus. The effects of PRKRA on PC were evaluated in vivo by cell-derived xenografts. The downstream genes of PRKRA were screened by transcriptome sequencing. The regulation of the target gene was validated by RT-qPCR, western blot, ChIP and dual luciferase reporter assay. Besides, the correlation between PRKRA and gemcitabine sensitivity was investigated by PC organoids. Results: PRKRA was significantly overexpressed in PC tissues and independently associated with poor prognosis. PRKRA promoted the proliferation, migration, and chemoresistance of PC cells. The proliferation of PC organoids was decreased by PRKRA knockout. The growth and chemoresistance of xenografts were increased by PRKRA overexpression. Mechanistically, PRKRA upregulated the transcription of MMP1 via NF-κB pathway. ChIP and dual luciferase reporter assay showed that NF-κB subunit P65 could bind to the promoter of MMP1. The sensitivity of PC organoids to gemcitabine was negatively correlated with the expression of PRKRA and MMP1. Conclusions: Our study indicated that the PRKRA/NF-κB/MMP1 axis promoted the progression of PC and may serve as a potential therapeutic target and prognosis marker.

Comparing the clinical value of baseline [68 Ga]Ga-FAPI-04 PET/CT and [18F]F-FDG PET/CT in pancreatic ductal adenocarcinoma: additional prognostic value of the distal pancreatitis.

PURPOSE: Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images. METHODS: Patients with suspected localized PDAC on CE-CT were recruited for static [68 Ga]Ga-FAPI-04 and 18[F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic 68 Ga-FAPI-04 PET/CT. The diagnostic and staging performances of the static PET/CT results were evaluated by delineating regions of interest in the primary tumor, whole pancreas, and distal pancreas in both types of scans and then evaluating correlations between the PET/CT findings and clinicopathological characteristics. Furthermore, Kaplan-Meier and hazard ratio (log-rank) methods were used to evaluate the prognostic value of the combined dynamic [68 Ga]Ga-FAPI-04 and static [18F]F-FDG PET/CT method. RESULTS: We included 49 patients with histologically confirmed PDAC adenocarcinomas; 32 underwent 60-min dynamic [68 Ga]Ga-FAPI-04 PET/CT imaging simultaneously. The static [68 Ga]Ga-FAPI-04 method had significantly higher accuracy and uptake values than the static [18F]F-FDG method for primary PDAC lesions, metastatic lymph nodes, and distal metastases. Furthermore, 18.4% and 10.2% of the patients' stages changed after using the [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT methodologies, respectively, compared to the CE-CT-designated stage. The Ki values obtained from dynamic [68 Ga]Ga-FAPI-04 PET/CT did not differ between PDAC and distal obstructive pancreatitis lesions. Pathologically enlarged tumor size, poor differentiation, and perineural invasion were associated with increased [68 Ga]Ga-FAPI-04 uptake but not with [18F]F-FDG uptake. The preoperative prognostic performance of [68 Ga]Ga-FAPI-04 was better than that of [18F]F-FDG. Interestingly, combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG uptake results in the whole pancreas could further stratify patients based on their postoperative prognosis. CONCLUSION: 6[68 Ga]Ga-FAPI-04 PET/CT was more sensitive and accurate than [18F]F-FDG PET/CT for tumor, node, and metastasis staging of PDAC identified on CE-CT. Additionally, [68 Ga]Ga-FAPI-04 uptake was significantly associated with pathologically aggressive tumor features. Combined [68 Ga]Ga-FAPI-04 and [18F]F-FDG PET/CT findings improved the prognostic value, potentially providing a non-invasive guide for clinical management. Finally, increased fibroblast activity in PDAC-induced obstructive pancreatitis may be associated with poor patient survival rates.

Genomic analysis and filtration of novel prognostic biomarkers based on metabolic and immune subtypes in pancreatic cancer.

PURPOSE: Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer METHODS: Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC RESULTS: High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids CONCLUSION: The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC.

Comprehensive study of clinical features, prognostic factors, and survival in patients with pancreatic solid pseudopapillary neoplasms based on the 2019 WHO classification.

BACKGROUND: Pancreatic solid pseudopapillary neoplasms (pSPNs) are a rare tumor type with a limited understanding of their clinical characteristics and survival outcomes. We aimed to investigate potential prognostic factors among the existing clinical features in patients diagnosed with pSPN. METHODS: For this study, we utilized data from the Surveillance Epidemiology and End Results (SEER) database, specifically selecting patients with a histology type of pSPN from the years 2000 to 2019. Subsequently, we conducted both univariate and multivariate Cox regression analyses in a systematic manner to identify potential prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in the selected group of patients. To assess the disparity in OS and CSS among different clinical features and treatments, Kaplan-Meier curves were generated. Furthermore, utilizing the results obtained from the multivariate analysis, we developed a nomogram predictive model to effectively forecast the prognosis of patients diagnosed with pSPN. Calibration plots were presented to demonstrate the predictive accuracy and reliability of the nomogram predictive model. RESULTS: The study comprised a total of 433 participants, with 85.7% of the patients diagnosed with pSPN being female and the remaining 14.3% being male. The Kaplan-Meier curves indicated that patients with pSPN who underwent primary tumor resection (PTR) and those who were younger than 70 years old had significantly improved OS and CSS compared to those who did not undergo PTR or were aged 70 years or older, respectively (P < 0.001). Male patients diagnosed with pSPN exhibited poor OS compared to female pSPN patients (P = 0.015). The multivariate Cox regression analysis indicated that age (OS: HR = 1.055, 95% CI = 1.027-1.084, P < 0.001. CSS: HR = 1.054, 95% CI = 1.019-1.091, P = 0.002) and PTR (OS: HR = 6.074, 95% CI = 1.922-19.194, P = 0.002. CSS: HR = 4.912, 95% CI = 1.188-20.312, P = 0.028) were independent prognostic factors for both OS and CSS. Moreover, tumor size (≥ 5 vs < 5 cm CSS: HR = 4.788, 95% CI = 1.012-22.661, P = 0.048) was an independent prognostic factor for CSS. The independent prognostic factors identified through the multivariate Cox regression analysis were utilized to construct a nomogram model for predicting both OS and CSS in patients with pSPN. The accuracy of the nomogram model was visually testified by the calibration plot with acceptable predictive performance. CONCLUSION: Although the majority of patients diagnosed with pSPN are females, it was observed that male patients tend to have poorer OS compared to their female counterparts. The independent prognostic factors identified in the study were age and PTR, which were associated with both OS and CSS. Tumor size was an independent prognostic factor for CSS. Patients who underwent PTR exhibited improved OS and CSS outcomes. The developed nomogram and corresponding reference table provided promising prognostic predictions for pSPN outcoms, serving as a valuable resource for clinicians and patients alike.