Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose‐dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere‐formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA‐mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC‐killer.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. In this study, we found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. We confirmed that the expression level of NOL12 was upregulated in human HCC tissues and cell lines by RT-qPCR. High expression of NOL12 is associated with worse reduced overall survival (OS), high pathological grade, node metastasis, and advanced clinical stage in patients with HCC. Moreover, knockdown of NOL12 dramatically inhibits the proliferation and metastasis of HCC cells in vitro and in vivo. CIBERSORTx analysis revealed that twelve types of tumor-infiltrating immune cells (TICs) are correlated with NOL12 expression. The risk signature based on 8 NOL12-related genes is an independent prognostic factor for patients with HCC. The OS rate of patients in the low-risk score group was better than that in the high-risk score group. In addition, the total tumor mutation burden (TMB) in the high-risk score group increased significantly, and the risk scores could be used as an alternative indicator of immune checkpoint inhibitor (ICI) response. In conclusion, our findings indicated that NOL12 might be involved in the progression of HCC and can be used as a potential therapeutic target. Moreover, the NOL12-related risk signature may have predictive relevance with regard to ICI therapy.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

BACKGROUND Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly affects young women. AIM To evaluate the impact of parenchyma-preserving surgical methods (PPMs, including enucleation and central pancreatectomy) in the treatment of SPN patients. METHODS From 2013 to 2019, patients who underwent pancreatectomy for SPNs were retrospectively reviewed. The baseline characteristics, intraoperative index, pathological outcomes, short-term complications and long-term follow-up data were compared between the PPM group and the conventional method (CM) group. RESULTS In total, 166 patients were included in this study. Of them, 33 patients (19.9%) underwent PPM. Most of the tumors (104/166, 62.7%) were found accidentally. Comparing the parameters between groups, the hospital stay d (12.35 vs 13.5 d, P = 0.49), total expense (44213 vs 54084 yuan, P = 0.21), operation duration (135 vs 120 min, P = 0.71), and intraoperative bleeding volume (200 vs 100 mL, P = 0.49) did not differ between groups. Regarding pathological outcomes, tumor size (45 vs 32 mm, P = 0.07), Ki67 index ( P = 0.53), peripheral tissue invasion (11.3% vs 9.1%, P = 0.43) and positive margin status (7.5% vs 6%, P = 0.28) also did not differ between groups. Moreover, PPM did not increase the risk of severe postoperative pancreatic fistula (3.8% vs 3.0%, P = 0.85) or tumor recurrence (3.0% vs 6.0%, P = 0.39). However, the number of patients who had exocrine insufficiency during follow-up was significantly lower in the PPM group (21.8% vs 3%, P = 0.024). CM was identified as an independent risk factor for pancreatic exocrine insufficiency (odds ratio = 8.195, 95% confident interval: 1.067-62.93). CONCLUSION PPM for SPN appears to be feasible and safe for preserving the exocrine function of the pancreas.