Development and validation of web calculators to predict early recurrence and long-term survival in patients with duodenal papilla carcinoma after pancreaticoduodenectomy.

BACKGROUND: Duodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop web calculators to predict early recurrence (ER) (within two years after surgery) and long-term survival in patients with DPC after PD. METHODS: Patients with DPC after radical PD were included. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Two web calculators were developed based on independent risk factors in the training cohort and then tested in the validation cohort. RESULTS: Of the 251 patients who met the inclusion criteria, 180 and 71 patients were enrolled in the training and validation cohorts, respectively. Multivariate logistic regression analysis revealed that tumor size [Odds Ratio (OR) 1.386; 95% confidence interval (CI) 1070-1.797; P = 0.014]; number of lymph node metastasis (OR 2.535; 95% CI 1.114-5.769; P = 0.027), perineural invasion (OR 3.078; 95% CI 1.147-8.257; P = 0.026), and tumor differentiation (OR 3.552; 95% CI 1.132-11.152; P = 0.030) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.759 and 0.729 in predicting ER in the training and the validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with single variable. CONCLUSIONS: This study developed and validated two web calculators that can predict ER and long-term survival in patients with DPC with high degree of stability and accuracy.

AGDF-Net: Attention-Gated and Direction-Field-Optimized Building Instance Extraction Network.

Building extraction from high-resolution remote sensing images has various applications, such as urban planning and population estimation. However, buildings have intraclass heterogeneity and interclass homogeneity in high-resolution remote sensing images with complex backgrounds, which makes the accurate extraction of building instances challenging and regular building boundaries difficult to maintain. In this paper, an attention-gated and direction-field-optimized building instance extraction network (AGDF-Net) is proposed. Two refinements are presented, including an Attention-Gated Feature Pyramid Network (AG-FPN) and a Direction Field Optimization Module (DFOM), which are used to improve information flow and optimize the mask, respectively. The AG-FPN promotes complementary semantic and detail information by measuring information importance to control the addition of low-level and high-level features. The DFOM predicts the pixel-level direction field of each instance and iteratively corrects the direction field based on the initial segmentation. Experimental results show that the proposed method outperforms the six state-of-the-art instance segmentation methods and three semantic segmentation methods. Specifically, AGDF-Net improves the objective-level metric AP and the pixel-level metric IoU by 1.1%~9.4% and 3.55%~5.06%.

Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. METHODS: mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. RESULTS: Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. CONCLUSIONS: We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment.

Impact of Postoperative Complications on Long-Term Survival After Resection of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Controversy exists over the relationship between postoperative complications (POCs) and long-term survival for hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of POCs on overall survival (OS) and disease-free survival (DFS) for HCC after liver resection. PATIENTS AND METHODS: The PubMed, EMBASE, and Cochrane Library databases were used to search for eligible studies published through 18 April 2020, and studies comparing the long-term outcomes between HCC patients with and without POCs after hepatectomy were included. A random-effects model was used to calculate the pooled hazard ratio (HR) with a 95% confidence interval (CI). Subgroup analysis and meta-regression were performed to assess the potential influence of study-, patient-, and tumor-related factors on the relationship between POCs and oncologic outcomes and to adjust their effect. This study was registered at the International Prospective Register of Systematic Reviews (CRD42019136109). RESULTS: Thirty-seven studies, including 14,096 patients, were deemed eligible and included in this study. Compared with those without POCs, patients who developed POCs had a significant reduction in OS (HR 1.39, 95% CI 1.28-1.50, P < 0.001; prediction interval 1.04-1.85) and tended to have worse DFS (HR 1.25, 95% CI 1.16-1.35, P < 0.001; prediction interval 0.98-1.60). Contour-enhanced funnel plots suggested a risk of publication bias. Subgroup analysis and meta-regression showed that POCs remained a threat to OS and DFS regardless of the influence of clinicopathological factors. CONCLUSION: This study demonstrated that POCs had an adverse impact on OS and DFS in HCC patients after liver resection.

Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA-SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown. METHODS: We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence-free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C-index). RESULTS: A total of 40 iCCA-SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA-SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation. CONCLUSION: The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients.

Resection of retrohepatic inferior vena cava without reconstruction in ex vivo liver resection and autotransplantation: a retrospective study.

BACKGROUND: Retrohepatic inferior vena cava (RIVC) resection without reconstruction in ex vivo liver resection and autotransplantation (ERAT) for advanced alveolar echinococcosis (HAE) is unclear. METHODS: This is a retrospective study of consecutive patients referred to our hospital from 2014 to 2018. Depending on the presence of a rich collateral circulation and stable blood volume in ERAT, patients did not rebuild the RIVC. Then, patients were selected some appropriate revascularization techniques for the hepatic and renal veins. Finally, all ERAT procedures were completed, and short- and long-term outcomes were observed. RESULTS: Five advanced HAE patients underwent ERAT without RIVC reconstruction. One patient died of circulatory failure 1 day after surgery. Another four patients, with a median follow-up duration of 18 months (range, 10-25 months), demonstrated normal liver and kidney function, no thrombosis and no HAE recurrence. CONCLUSIONS: Through the long-term results of ERAT, the pros and cons of not reconstructing the RIVC need to be re-examined. In cases with a rich collateral circulation, the RIVC cannot be reconstructed. However, in cases requiring the resection of multiple organs, RIVC without reconstruction was prudential.

[The Predictive Value of Perioperative Inflammatory Indicatorsin Prognosis of the Intrahepatic Cholangiocarcinoma Patients after Hepatectomy].

OBJECTIVE: To evaluate the effect of perioperative inflammatory indicators on the prognosis of the patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy. METHODS: The clinical data of 231 ICC patients in the West China Hospital of Sichuan University from December 2006 to December 2016 were retrospectively collected. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) and platelet-to-lymphocyte ratio (PLR) of patients during the perioperative period (pre-operation, postoperative day 3 and day 5) were analyzed. The X-tile software was used to determine the optimal cut-off values of NLR, d-NLR and PLR in pre-operation, postoperative day 3 and day 5. Based on the cut-off values, all patients were divided into high level group and low level group, and Kaplan-Meier methods were used to analyze the correlations of NLR, d-NLR and PLR with the disease-free survival (DFS) and overall survival (OS) of patients. Univariate and multivariate Cox regression models were applied to assess the prognostic values of NLR, d-NLR and PLR. Nomogram was established to predict the prognosis for ICC patients, and the predicting accuracy was evaluated by the Consistency index ( C-index). RESULTS: A total of 231 ICC patients including 115 males and 116 females were enrolled into this study, and the proportion of patients aged <60 years was 57.1%. Among the patients enrolled, 161 patients (69.7%) recurred and 156 patients (67.5%) died after hepatectomy. The median time of DFS and OS were 8.9 and 12.5 months respectively. The Kaplan-Meier curves showed that d-NLR and NLR levels in pre-operation, postoperative day 3 and day 5, together with the preoperative PLR level were correlated with the time of DFS ( P<0.05). Meanwhile, d-NLR and PLR levels in pre-operation, postoperative day 3 and day 5, together with the NLR level in pre-operation and postoperative day 3 were correlated with the time of OS ( P<0.05). Univariate and multivariate Cox regression model analysis suggested that high level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of poor DFS. High level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of OS. The level of PLR level was not correlated with DFS and OS. The C-index values of nomogram for predicting DFS and OS were 0.738 (95% confidence interval: 0.699-0.777) and 0.778 (95% confidence interval: 0.758-0.818), respectively. CONCLUSION: High level of the preoperative NLR, preoperative d-NLR and NLR on postoperative day 3 in ICC patients indicate poor prognosis, and PLR has no prognostic value for ICC patients after hepatectomy.

Identification of core genes and outcomes in hepatocellular carcinoma by bioinformatics analysis.

Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. However, the mechanistic relationships among various genes and signaling pathways are still largely unclear. In this study, we aimed to elucidate potential core candidate genes and pathways in HCC. The expression profiles GSE14520, GSE25097, GSE29721, and GSE62232, which cover 606 tumor and 550 nontumour samples, were downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, HCC RNA-seq datasets were also downloaded from the Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were filtered using R software, and we performed gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using the online databases DAVID 6.8 and KOBAS 3.0. Furthermore, the protein-protein interaction (PPI) network complex of these DEGs was constructed by Cytoscape software, the molecular complex detection (MCODE) plug-in and the online database STRING. First, a total of 173 DEGs (41 upregulated and 132 downregulated) were identified that were aberrantly expressed in both the GEO and TCGA datasets. Second, GO analysis revealed that most of the DEGs were significantly enriched in extracellular exosomes, cytosol, extracellular region, and extracellular space. Signaling pathway analysis indicated that the DEGs had common pathways in metabolism-related pathways, cell cycle, and biological oxidations. Third, 146 nodes were identified from the DEG PPI network complex, and two important modules with a high degree were detected using the MCODE plug-in. In addition, 10 core genes were identified, TOP2A, NDC80, FOXM1, HMMR, KNTC1, PTTG1, FEN1, RFC4, SMC4, and PRC1. Finally, Kaplan-Meier analysis of overall survival and correlation analysis were applied to these genes. The abovementioned findings indicate that the identified core genes and pathways in this bioinformatics analysis could significantly enrich our understanding of the development and recurrence of HCC; furthermore, these candidate genes and pathways could be therapeutic targets for HCC treatment.

Synchronous hepatectomy and splenectomy vs hepatectomy for selected patients with hepatocellular carcinoma and clinically significant portal hypertension: A systematic review and meta-analysis.

This review aimed to evaluate the safety, feasibility, and effectiveness of synchronous hepatectomy and splenectomy for selected patients with hepatocellular carcinoma and clinically significant portal hypertension compared to hepatectomy alone. A systematic search in electronic databases was conducted. A total of 8 studies including 1445 patients were reviewed. While perioperative safety was satisfactory, synchronous hepatectomy and splenectomy were associated with a significant improvement of 5-year overall survival (odds ratio = 1.81; 95% confidence interval: 1.35, 2.42; P < 0.0001).

Outcomes of different surgical resection techniques for end-stage hepatic alveolar echinococcosis with inferior vena cava invasion.

BACKGROUND: Hepatic alveolar echinococcosis (HAE) lesions with inferior vena cava (IVC) invasion require combined resection of the liver and IVC. The outcomes of different surgical treatments, including in situ, ante situm and ex vivo resection, remain unclear. METHODS: A total of 71 consecutive HAE patients who underwent hepatectomy with retrohepatic IVC resection were included. The patients were divided into ex vivo liver resection and autotransplantation (ERAT) group (n = 45) and in vivo resection group (n = 26). These techniques were assessed for feasibility and short- and long-term outcomes. RESULTS: There were no significant differences with respect to postoperative complications and mortality between the ERAT and in vivo resection groups. The causes of mortality were liver failure in 3 patients, hemorrhagic shock in 1 patient, intra-abdominal bleeding in 1 patient, and acute cerebral hemorrhage in 1 patient. During a median of 22 months followed-up time, 2 patients developed ascites because of venous outflow stenosis, and 1 patient developed biliary stenosis in the ERAT group. The distant metastasis, local recurrence, and mortality rates were 0%, 1.4%, and 8.5%, respectively. CONCLUSION: Combined liver resection and reconstruction of the IVC can be safely performed in selected patients with in situ, ante situm, and ex vivo resection.

Copper-mediated trifluoromethylation of propargyl acetates leading to trifluoromethyl-allenes.

A copper-mediated trifluoromethylation of propargyl acetates with S-(trifluoromethyl)diphenylsulfonium triflate leading to trifluoromethylated allenes in moderate to excellent yields is described.

The causal effect of mTORC1-dependent circulating protein levels on nonalcoholic fatty liver disease: A Mendelian randomization study.

BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a crucial role in the development of nonalcoholic fatty liver disease (NAFLD). However, the causal effect of mTOR downstream proteins on NAFLD remains unknown. AIMS: We conducted a two-sample Mendelian randomization (MR) study to investigate whether the mTOR-dependent circulating proteins, including Eukaryotic Initiation Factor 4E Binding Proteins (eIF4EBPs), Ribosomal Protein S6K kinase 1 (RP-S6K), Eukaryotic Initiation Factor 4E (eIF4E), Eukaryotic Initiation Factor 4A (eIF4A) and Eukaryotic Initiation Factor 4 G (eIF4G), have causal effects on the risk of NAFLD. METHODS: The causal estimate was evaluated with the inverse-variance weighted (IVW) method in discovery stage and validation stage. The single-nucleotide polymorphisms (SNPs) were selected to genetically predict exposures from Genome-Wide Association Studies (GWAS). Exposures with statistically significant effects in the discovery dataset would be further validated in the validation dataset. RESULTS: MR study revealed that eIF4E had a causal effect on NAFLD in both discovery stage (OR = 1.339, P = 0.037) and validation stage (OR = 1.0007, P = 0.022). Sensitivity analyses confirmed robustness of the results. CONCLUSION: The genetically predicted higher level of mTOR-dependent eIF4E in plasma might have a causal effect on the occurrence of NAFLD.

Enhancing regeneration and repair of long-distance peripheral nerve defect injuries with continuous microcurrent electrical nerve stimulation.

Introduction: Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. Methods: The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. Results: The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. Discussion: While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.

The effects of different impeller combinations in the Sphingan WL gum fermentation process.

The fermentation of the high-viscosity polysaccharide WL gum has always been associated with poor mass transfer. Appropriate impeller configurations are key factors in maintaining homogeneity and sufficient mass transfer conditions. Therefore, a flat-folded disc turbine impeller (FFDT) taking into account both the reduced cavitation effect and the increased contact area was designed. Besides, a curved cross impeller (CC) and a fishbone-shaped impeller (FS) generating axial flow were also designed. The energy consumption and efficiency of the designed impellers and eight reported impellers were evaluated through fermentation and principal component analysis (PCA). Compared to the commonly-used six-blade flat-blade disc turbine (FBDT), the ungassed power number of FFDT was reduced by 50 %. Combinations of six-blade Brumajin impeller (BM) + FFDT and CC + FFDT produced high WL gum production and viscosity (34.0 g/L, 35.50 g/L, and 62.64 Pa·s, 61.68 Pa·s, respectively) and were suitable impellers for WL biosynthesis. WL gum from BM + FFDT showed higher viscosity, viscoelasticity, and molecular weight than that from FBDT + FBDT. In addition, fewer amino acids and pyruvic acid intermediates were formed using BM + FFDT, indicating a greater metabolic flux towards WL gum synthesis. This work provided an important reference for the design of impellers in high-viscosity fermentation systems.

Silencing of RAB42 down-regulated PD-L1 expression to inhibit the immune escape of hepatocellular carcinoma cells through inhibiting the E2F signaling pathway.

OBJECTIVE: To investigate the mechanistic role of RAB42 and corresponding regulatory path in hepatocellular carcinoma (HCC). METHODS: The expression of RAB42 in HCC tissue was checked by RT-qPCR and immunohistochemical staining assay. Cell proliferation was checked by colony formation and CCK-8 assay. Cell apoptosis and cycle distribution were analyzed with flow cytometry. The relevance of RAB42 and PD-L1 was analyzed from TCGA database. The binding of E2F1 to PD-L1 was detected by JASPAR database, luciferase and ChIP assay. The expression of PD-L1, cell apoptosis- and E2F pathway-related proteins were checked by western blotting. RESULTS: RAB42 was highly expressed in HCC tissue. RAB42 silencing could inhibit proliferation and induce G1 phase arrest and apoptosis of HCC cells. TCGA database disclosed that PD-L1 was highly associated with RAB42 expression. Silencing of RAB42 could retard PD-L1 expression in HCC cells. GSEA analysis showed RAB42 could activate E2F signaling pathway. Silencing of RAB42 could observably weaken the expression of E2F1, CDK1 and CDC20 in HCC cells. JASPAR database predicted the binding site between E2F1 and PD-L1, and E2F1 overexpression could promote PD-L1 expression. Overexpression of E2F1 could reverse the biological function of RAB42 silencing in HCC cells. CONCLUSION: Silencing of RAB42 could down-regulate PD-L1 expression to inhibit immune escape through inhibiting E2F signaling pathway in HCC cells. RAB42 may become a novel clinical diagnostic and therapy marker for HCC.

Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.

Under normal conditions, insulin promotes hepatic de novo lipogenesis (DNL). However, during insulin resistance (IR), when insulin signalling is blunted and accompanied by hyperinsulinaemia, the promotion of hepatic DNL continues unabated and hepatic steatosis increases. Here, we show that WD40 repeat-containing protein 6 (WDR6) promotes hepatic DNL during IR. Mechanistically, WDR6 interacts with the beta-type catalytic subunit of serine/threonine-protein phosphatase 1 (PPP1CB) to facilitate PPP1CB dephosphorylation at Thr316, which subsequently enhances fatty acid synthases transcription through DNA-dependent protein kinase and upstream stimulatory factor 1. Using molecular dynamics simulation analysis, we find a small natural compound, XLIX, that inhibits the interaction of WDR6 with PPP1CB, thus reducing DNL in IR states. Together, these results reveal WDR6 as a promising target for the treatment of hepatic steatosis.

The Impact of a History of Different Other Cancers on the Long-Term Outcomes of Patients with Intrahepatic Cholangiocarcinoma: A Population-Based Analysis.

Background: The characteristics and outcomes of patients with intrahepatic cholangiocarcinoma (ICC) with prior malignancy are poorly clarified. This study is aimed at exploring the impact of prior malignancy on the long-term outcomes of ICC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) program, ICC patients diagnosed between 2004 and 2018 were identified. Kaplan-Meier curves and Cox analysis were used to evaluate the impact of prior malignancy on the prognosis of ICC patients. Results: A total of 9667 ICC patients were identified; among them, 782 (8.09%) had a history of prior cancer. Prostate, breast, colorectal, bladder, and liver/gallbladder/other biliary cancers were the most common types of prior cancer. Patients with prior cancer had better tumor-related profiles than those without prior cancer, namely, the former patients showed a lower proportion of positive AFP levels and vascular invasion, a lower AJCC stage, a smaller tumor size, and a lower stage of tumor grade. The median survival times after the diagnosis of ICC were 10 and 11.5 months for patients with and without prior cancer, respectively. Multivariate regression analysis suggested that prior cancer did not contribute to inferior overall survival (OS, HR 0.870, 95% CI 0.797-0.950, and p = 0.002) or cancer-specific survival (CSS, HR 0.820, 95% CI 0.741-0.906, and p < 0.001). Conclusions: A history of prior cancer does not lead to worse OS or CSS for ICC patients. The exclusion of patients with prior cancer from clinical trials should be reconsidered.

Analysis of N6-methyladenosine-related lncRNAs in the tumor immune microenvironment and their prognostic role in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a rare solid malignancy with a poor prognosis. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and progression. However, little is known about the role of m6A-related lncRNAs in PC. METHODS: m6A-related lncRNAs were extracted by Pearson analysis, and then prognosis-related lncRNAs were filtered from the m6A-related lncRNAs by univariate Cox regression analysis. Based on the expression patterns of the prognosis-related lncRNAs, samples were classified into distinct clusters. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct a m6A-lncRNA-related prognostic signature for PC patients. Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) values were used to evaluate the prognostic ability of the model. RESULTS: A total of 178 tumor and 4 normal samples were extracted from The Cancer Genome Atlas (TCGA) database in our study. Based on the expression of 12 filtered prognosis-related lncRNAs, two distinct clusters were eventually identified; these clusters were characterized by differences in the tumor immune microenvironment (TIME) and prognosis. A risk model comprising ten m6A-related lncRNAs was identified as an independent predictor of prognosis. ROC analysis revealed that this model had an acceptable prognostic value for PC patients. The prognostic signature was related to the TIME and the expression of critical immune checkpoint molecules. CONCLUSION: This study comprehensively assessed the expression pattern and prognostic value of m6A-related lncRNAs in PC. The different clusters correlated with distinct TIMEs and prognoses. The study also constructed a ten-gene signature prognostic model based on m6A-related lncRNAs, which showed good accuracy in predicting overall survival.