Sorafenib and transarterial chemoembolization (TACE) are recommended therapies for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. Between August 2004 and November 2014, 104 patients with BCLC stage B/C HCC were enrolled at the Affiliated Tumor Hospital of Guangxi Medical University, China. Forty-eight patients were treated with sorafenib alone (sorafenib group) and 56 with TACE plus sorafenib (TACE + sorafenib group). Baseline demographic/clinical data were collected. The primary outcomes were median overall survival (OS) and progression-free survival (PFS). Secondary outcomes were overall response rate (ORR) and sorafenib-related adverse events (AEs). Baseline characteristics associated with disease prognosis were identified using multivariate Cox hazards regression. The mean age of the 104 patients (94 males; 90.38%) was 49.02 ± 12.29 years. Of the baseline data, only albumin level (P = 0.028) and Child-Pugh class (P = 0.017) differed significantly between groups. Median OS did not differ significantly between the sorafenib and TACE + sorafenib groups (18.0 vs. 22.0 months, P = 0.223). Median PFS was significantly shorter in the sorafenib group than that in the TACE + sorafenib group (6.0 vs. 8.0 months, P = 0.004). Six months after treatments, the ORRs were similar between the sorafenib and TACE + sorafenib groups (12.50% vs. 18.75%, P = 0.425). The rates of grade III–IV adverse events in sorafenib and TACE + sorafenib groups were 29.2% vs. 23.2%, respectively. TACE plus sorafenib treatment (HR = 0.498, 95% CI = 0.278–0.892), no vascular invasion (HR = 0.354, 95% CI = 0.183–0.685) and Child-Pugh class A (HR = 0.308, 95% CI = 0.141–0.674) were significantly associated with better OS, while a larger tumor number was predictive of poorer OS (HR = 1.286, 95% CI = 1.031–1.604). TACE plus sorafenib treatment (HR = 0.461, 95% CI = 0.273–0.780) and no vascular invasion (HR = 0.557, 95% CI = 0.314–0.988) were significantly associated with better PFS. Compared with sorafenib alone, combining TACE with sorafenib might prolong survival and delay disease progression in patients with advanced HCC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer‐related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single‐cell RNA sequencing (scRNA‐seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co‐localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha‐smooth muscle actin (α‐SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis‐associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

MiRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA target gene prediction databases, and their functions were analyzed using the online tool WebGestalt. miR-1180-3p expression was significantly upregulated in 88 HCC tissues compared with non-tumor liver tissues (0.004 ± 0.009 vs. 0.002 ± 0.002, t = − 2.099, P = 0.038). Additionally, we found that the expression levels of miR-1180-3p were significantly correlated with tumor number (χ² = 9.157, P = 0.006) and MVI (χ² = 11.354, P = 0.003). Based on Kaplan–Meier analysis, patients with high miR-1180 expression had a shorter overall survival than those with low miR-1180-3p expression (P = 0.002). Furthermore, multivariate Cox analyses indicated that miR-1180-3p expression was an independent prognostic factor for overall survival (HR = 13.36, 95% CI 1.16, 153.69, P = 0.038). In addition, a total of 733 target genes of miR-1180-3p were found from three prediction databases. The GO analyses demonstrated that the target genes were closely related to the proliferation and malignancy of tumors. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Pathways in cancer, the Ras signaling pathway, and the MAPK signaling pathway. In conclusion, we demonstrate that miR-1180-3p is upregulated in HCC and is associated with a poor prognosis. Thus, miR-1180-3p might be useful as a prognostic marker for HCC.

Objective: This study aimed to investigate potential causal relationships between circulating metabolites and breast cancer risk using Mendelian randomization (MR) analysis.Materials and Methods: Summary-level genome-wide association study (GWAS) datasets for 249 circulating metabolites were obtained from the UK Biobank. GWAS datasets for estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer were acquired from previous studies based on the Combined Oncoarray. Instrumental variables (IVs) were selected from single nucleotide polymorphisms (SNPs) associated with circulating metabolites, and MR analyses were conducted using the inverse-variance weighted (IVW) method as the primary analysis, with additional sensitivity analyses using other MR methods. Odds ratios (OR) and 95% confidence interval (CI) were used to estimate the association of circulating metabolites with breast cancer risk.Results: The IVW analysis revealed significant causal relationships between 79 circulating metabolites and ER + breast cancer risk, and 10 metabolites were significantly associated with ER-breast cancer risk. Notably, acetate (OR = 1.12, P = 0.03), HDL cholesterol (OR = 1.09, P < 0.001), ration of omega-6 fatty acids to total fatty acids ratio (OR = 1.09, P = 0.01), and phospholipids in large LDL (OR = 1.09, P < 0.001) were linked to an increased risk of ER + breast cancer, while linoleic acid (OR = 0.91, P < 0.001) monounsaturated fatty acids (OR = 0.91, P < 0.001), and total lipids in LDL (OR = 0.91, P < 0.001) were associated with a decreased risk. In ER-breast cancer, glycine, citrate, HDL cholesterol, cholesteryl esters in HDL, cholesterol to total lipids ratio in very large HDL, and cholesterol in large LDL were associated with an increased risk, while the free cholesterol to total lipids in very large HDL was linked to a decreased risk.Conclusion: This MR approach underscores aberrant lipid metabolism as a key process in breast tumorigenesis, and may inform future prevention and treatment strategies. To further elucidate the underlying mechanisms and explore the potential clinical implications, additional research is warranted to validate the observed associations in this study.

Background: There have been many reports on midkine as a promising marker in the diagnosis of hepatocellular carcinoma (HCC). However, the results are inconsistent and even conflicting.Methods: This meta‐analysis was performed to investigate the accuracy of midkine in the diagnosis of HCC. Meta‐DiSc 1.4 software was used to extract data and to calculate the overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Data are presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance.Results: Ten studies with a total of 753 HCC patients and 977 non‐HCC patients were included. The overall pooled diagnostic data were as follows: the pooled sensitivity of 0.86 (95% confidence interval [CI]: 083–0.88), the pooled specificity of 0.75 (95% CI: 0.73–0.78), the pooled PLR of 4.71 (95% CI: 2.80–7.90), the pooled NLR of 0.18 (95% CI: 0.11–0.30), and the pooled DOR of 36.83 (95% CI: 13.56–100.05). The area under curve value was 0.9266 in the overall SROC curve.Conclusion: Midkine has moderate diagnostic accuracy for HCC. Due to the design limitations, results inpublished studies should be carefully interpreted. In addition, more well‐designed studies with large sample sizes should be performed to rigorously evaluate the diagnostic accuracy of the MDK.