Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma.

The NK cell is an important component of the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC), also plays a significant role in PDAC development. This study aimed to explore the relationship between NK cell marker genes and prognosis, immune response of PDAC patients. By scRNA-seq data, we found the proportion of NK cells were significantly downregulated in PDAC and 373 NK cell marker genes were screened out. By TCGA database, we enrolled 7 NK cell marker genes to construct the signature for predicting prognosis in PDAC patients. Cox analysis identified the signature as an independent factor for pancreatic cancer. Subsequently, the predictive power of signature was validated by 6 GEO datasets and had an excellent evaluation. Our analysis of relationship between the signature and patients' immune status revealed that the signature has a strong correlation with immunocyte infiltration, inflammatory reaction, immune checkpoint inhibitors (ICIs) response. The NK cell marker genes are closely related to the prognosis and immune capacity of PDAC patients, and they have potential value as a therapeutic target.

Establishment of a novel signature to predict prognosis and immune characteristics of pancreatic cancer based on necroptosis-related long non-coding RNA.

BACKGROUND: Necroptosis plays an important role in tumorigenesis and tumour progression. Long noncoding RNAs (lncRNAs) have been proven to be regulatory factors of necroptosis in various tumours. However, the real role of necroptosis-related lncRNAs (NRLs) and their potential to predict the prognosis of pancreatic cancer (PC) remain largely unclear. The goal of this study was to identify NRLs and create a predictive risk signature in PC, explore its prognostic predictive performance, and further assess immunotherapy and chemotherapy responses. METHODS: RNA sequencing data, tumour mutation burden (TMB) data, and clinical profiles of 178 PC patients were downloaded from The Cancer Genome Atlas (TCGA) database. NRLs were identified using Pearson correlation analysis. Then, patients were divided into the training set and the validation set at a 1:1 ratio. Subsequently, Cox and LASSO regression analyses were conducted to establish a prognostic NRL signature in the training set and validation set. The predictive efficacy of the 5-NRL signature was assessed by survival analysis, nomogram, Cox regression, clinicopathological feature correlation analysis, and receiver operating characteristic (ROC) curve analysis. Furthermore, correlations between the risk score (RS) and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anticancer drug sensitivity were analysed. Finally, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to validate the 5-NRLs. RESULTS: A 5-NRL signature was established to predict the prognosis of PC, including LINC00857, AL672291.1, PTPRN2-AS1, AC141930.2, and MEG9. The 5-NRL signature demonstrated a high degree of predictive power according to ROC and Kaplan‒Meier curves and was revealed to be an independent prognostic risk factor via stratified survival analysis. Nomogram and calibration curves indicated the clinical adaptability of the signature. Immune-related pathways were linked to the 5-NRL signature according to enrichment analysis. Additionally, immune cell infiltration, immune checkpoint molecules, somatic gene mutations and the half-maximal inhibitory concentration (IC50) of chemotherapeutic agents were significantly different between the two risk subgroups. These results suggested that our model can be used to evaluate the effectiveness of immunotherapy and chemotherapy, providing a potential new strategy for treating PC. CONCLUSIONS: The novel 5-NRL signature is helpful for assessing the prognosis of PC patients and improving therapy options, so it can be further applied clinically.

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods.

Background: As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated. Methods: Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson's correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature's predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied. Results: In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. Conclusion: The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

Organ-Sparing Pancreatectomy for Benign or Low-Grade Malignant Pancreatic Tumors: A Single-Center Experience with 101 Consecutive Patients.

BACKGROUND Pancreaticoduodenectomy (PD) and distal pancreatectomy with splenectomy (DPS) are considered the standard procedures for pancreatic lesions. However, long-term metabolic consequences of PD and DPS applied for benign or low-grade malignant tumors need to be addressed. This study aimed to investigate the short- and long-term outcomes of organ-sparing pancreatectomy for benign or low-grade malignant pancreatic tumors in our institution. MATERIAL AND METHODS The clinical data of 101 patients with benign or low-grade malignant pancreatic tumors who underwent organ-sparing pancreatectomy from January 2009 to September 2021 were retrospectively analyzed, including 40 tumor enucleations (EN), 22 central pancreatectomies (CP), 25 spleen-preserving distal pancreatectomies (SPDP), 7 pylorus-preserving pancreaticoduodenectomies (PPPD) and 7 duodenum-preserving pancreatic head resections (DPPHR). RESULTS The mean operative time, intraoperative blood loss, and length of hospital stay were 182.9±74.6 min, 191.9±127.8 mL, and 11.6±8.1 days, respectively. EN had the shortest operative time, while DPPHR had the longest operative time. The mean intraoperative blood loss of DPPHR and PPPD was significantly greater than the others (all P<0.05). The length of hospital stay of PPPD was longest. The overall morbidity was 33.6%. The reoperation rate was 1.0% and there was no mortality. The incidence of pancreatic endocrine insufficiency and exocrine insufficiency were 5.9% and 6.9%, respectively. None patients had tumor recurrence during the follow-up period. CONCLUSIONS Organ-sparing pancreatectomy is associated with acceptable perioperative risk and postoperative complications and better long-term outcomes in the aspects of preservation of function and curability in benign or low-grade malignant pancreatic tumors.