Zhengwen Cai

Background and Aim: The biological functions and clinical implications of lysophosphatidylcholine acyltransferase 1 (LPCAT1) remain unclarified in gastric cancer (GC). The aim of the current study was to explore the possible clinicopathological significance of LPCAT1 and its perspective mechanism in GC tissues.Materials and Methods: The protein expression and mRNA levels of LPCAT1 were detected from in‐house immunohistochemistry and public high‐throughput RNA arrays and RNA sequencing. To have a comprehensive understanding of the clinical value of LPCAT1 in GC, all enrolled data were integrated to calculate the expression difference and standard mean difference (SMD). The biological mechanism of LPCAT1 in GC was confirmed by computational biology and in vitro experiments. Migration and invasion assays were also conducted to confirm the effect of LPCAT1 in GC.Results: Both protein and mRNA expression levels of LPCAT1 in GC were remarkably higher than those in noncancerous controls. Comprehensively, the SMD of LPCAT1 mRNA was 1.11 (95% CI = 0.86–1.36) in GC, and the summarized AUC was 0.85 based on 15 datasets containing 1727 cases of GC and 940 cases of non‐GC controls. Moreover, LPCAT1 could accelerate the invasion and migration of GC by boosting the neutrophil degranulation pathway and disturbing the immune microenvironment.Conclusion: An increased level of LPCAT1 may promote the progression of GC.

Incorrect Funding In the published article, there was an error in the Funding statement. The funding from Guangxi key research and development program was omitted. The correct Funding statement appears below.FUNDINGThe authors declare that this study received funding from Guangxi key research and development program No. (GK) AB18221080, The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi (2020KY03036), Guangxi Medical University Foundation (GXMUYSF201918), Foundation of Guangxi Health and Family Planning Commission (Z20190581), Foundation of the Second Affiliated Hospital of Guangxi Medical University (hbrc202104). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Background: Machine learning is now well-developed in non-small cell lung cancer (NSCLC) radiotherapy. But the research trend and hotspots are still unclear. To investigate the progress in machine learning in radiotherapy NSCLC, we performed a bibliometric analysis of associated research and discuss the current research hotspots and potential hot areas in the future.Methods: The involved researches were obtained from the Web of Science Core Collection database (WoSCC). We used R-studio software, the Bibliometrix package and VOSviewer (Version 1.6.18) software to perform bibliometric analysis.Results: We found 197 publications about machine learning in radiotherapy for NSCLC in the WoSCC, and the journal Medical Physics contributed the most articles. The University of Texas MD Anderson Cancer Center was the most frequent publishing institution, and the United States contributed most of the publications. In our bibliometric analysis, “radiomics” was the most frequent keyword, and we found that machine learning is mainly applied to analyze medical images in the radiotherapy of NSCLC.Conclusion: The research we identified about machine learning in NSCLC radiotherapy was mainly related to the radiotherapy planning of NSCLC and the prediction of treatment effects and adverse events in NSCLC patients who were under radiotherapy. Our research has added new insights into machine learning in NSCLC radiotherapy and could help researchers better identify hot research areas in the future.

Background: Matrine, the main active ingredient in the traditional Chinese medical herb Sophora flavescens, has promising antitumor properties on tumor cell lines. However, the underlying molecular mechanisms remain to be clarified. This study explored the underlying molecular events for the anticancer effect of matrine, a plant alkaloid, on colon cancer cells in vitro and in vivo from the perspective of the DNA damage response. Methods: Colon cancer RKO (human colon cancer cells) cells were grown and transfected with checkpoint kinase 1 (CHK1) cDNA or vector-only, and then treated with or without matrine (0, 2, 4, or 8 µM) for transwell and comet assays, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), western blot, immunofluorescence experiments, enzyme-linked immunosorbent assay (ELISA), and subcutaneous tumorigenesis experiments of nude mice. Results: Matrine dose-dependently inhibited the cell migration and invasion capacity as well as induced DNA damage in RKO cells in vitro. In addition, matrine dose-dependently upregulated the expression of DNA single- and double-strand break marker proteins (γH2AX (γH2A histone family member X) and cleaved PARP1 (poly (ADP-ribose) polymerase 1)), DNA damage marker proteins, and E-cadherin; However, it downregulated the expression of vimentin and CHK1. Furthermore, compared with the matrine plus vector control group, CHK1 overexpression induced the cell migration and invasion abilities of RKO cells. CHK1 overexpression also reduced E-cadherin expression but induced vimentin expression in RKO cells. CHK1 overexpression suppressed the expression of the DNA damage-related proteins (γH2AX, cleaved PARP1, and PARP1) and E-cadherin but increased the expression of vimentin in RKO cells. Moreover, matrine could reduce the release of interleukin (IL)-1β and IL-8 in vivo, which compose the DNA damage secretory program (DDSP). In the subcutaneous tumorigenesis experiment of nude mice, it was confirmed by immunohistochemistry that CHK1 expression decreased and γH2AX expression increased after matrine treatment. Conclusions: Matrine was able to inhibit activation of the DNA damage response kinase CHK1, thereby inhibiting the DNA damage response and epithelial-mesenchymal transition (EMT) in colon cancer cells.

[This corrects the article on p. 1295 in vol. 10, PMID: 29887946.].

The present study investigated the sensitization of 5‑fluorouracil (5‑FU)‑resistant colon cancer cells in vitro, using oxymatrine, a Chinese herb, and a quinolizidine alkaloid compound extracted from the root of Sophora flavescens. The HCT‑8 colon cancer cell line and its 5‑FU‑resistant subline HCT‑8/5‑FU were treated with 5‑FU and oxymatrine, alone or in combination, at various doses. The cells were subsequently assessed for changes in cell viability, apoptosis and morphology and analyzed by fluorescence microscopy and western blotting. The data demonstrated that HCT‑8/5‑FU markedly increased the dose of 5‑FU required for the suppression of tumor cell viability (78.77±1.90 µg/ml vs. 9.20±0.96 µg/ml in parental HCT‑8 cells), whereas HCT‑8/5‑FU induced the tumor cell epithelial‑mesenchymal transition (EMT). By contrast, oxymatrine alone and in combination with 5‑FU altered HCT‑8/5‑FU cell morphology, apoptosis and EMT phenotypes. The combination of oxymatrine and 5‑FU reduced the protein expression of snail family transcriptional repressor 2 and vimentin, phosphorylated p65 and induced the expression of E‑cadherin, by inhibiting the nuclear factor κB (NF‑κB) signaling pathway. In conclusion, the data from the present study demonstrated that EMT was associated with 5‑FU chemoresistance in HCT‑8/5‑FU colon cancer cells, and that oxymatrine treatment was able to reverse such resistance. Oxymatrine may regulate tumor cell EMT and inactivate the NF‑κB signaling pathway, and may therefore serve as a potential therapeutic drug to reverse 5‑FU resistance in colon cancer cells.

MiR-182-5p, as a member of miRNA family, can be detected in lung cancer and plays an important role in lung cancer. To explore the clinical value of miR-182-5p in lung squamous cell carcinoma (LUSC) and to unveil the molecular mechanism of LUSC. The clinical value of miR-182-5p in LUSC was investigated by collecting and calculating data from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database, and real-time quantitative polymerase chain reaction (RT-qPCR). Twelve prediction platforms were used to predict the target genes of miR-182-5p. Protein-protein interaction (PPI) networks and gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of LUSC. The expression of miR-182-5p was significantly over-expressed in LUSC than in non-cancerous tissues, as evidenced by various approaches, including the TCGA database, GEO microarrays, RT-qPCR, and a comprehensive meta-analysis of 501 LUSC cases and 148 non-cancerous cases. Furthermore, a total of 81 potential target genes were chosen from the union of predicted genes and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in pathways related to biological processes. PPIs revealed the relationships between these genes, with EPAS1, PRKCE, NR3C1, and RHOB being located in the center of the PPI network. MiR-182-5p upregulation greatly contributes to LUSC and may serve as a biomarker in LUSC.

Background: Recent studies have reported that an elevated intracellular glutathione (GSH) level is associated with resistance of non-small cell lung cancer (NSCLC) cell lines to cisplatin (CDDP). It is well-known that GSH is widely used in the clinic as a hepatoprotective agent. However, whether exogenous GSH can affect the sensitivity of NSCLC cells to CDDP remains unclear. The aim of this study is to evaluate the role of exogenous GSH in the resistance of A549 cells to CDDP. Methods: The effect of GSH and CDDP on the proliferation of A549 cells was analyzed by MTT assay. Subsequent experiments were conducted in A549 cells divided into four groups: control group (untreated cells), GSH group (treated with 120 mu g/ml GSH for 48 N. CDDP group (treated with 10 mu G/ml CDDP for 48 h) and CDDP+GSH group (treated with 10 mu g/ml CDDP+120 mu g/ml GSH for 48 M. Apoptosis was detected by flow cytometry. Light microscopy, fluorescence microscopy and electron microscopy were performed to study morphologic and ultrastructural differences among the four groups of cells. Intracellular GSH level and gamma-GCS expression were determined by immunohistochemistry (IHC). Cellular platinum uptake was assessed by inductively coupled plasma mass spectrometry (ICP-MS). Quantitative RT-PCR analysis was performed to measure the expression of caspase3, caspase9, bax, bc1-2 and MDR-1. Western blot analysis was conducted to examine the protein levels of GST-n, MRP-1 and P-gp. Results: Growth inhibition and apoptosis were reduced in A549 cells in the CDDP+GSH group compared to those in the CDDP group 48 h post-treatment. Alterations in cellular morphology and ultrastructure, as well as typical characteristics of apoptosis, were observed. Intracellular GSH and gamma-GCS levels were elevated by exogenous administration of GSH; in contrast, cellular platinum concentration fell rapidly. Relative to the CDDP group, the CDDP+GSH group exhibited 47.92%, 47.82% and 63.75% downregulation in caspase3, caspase9 and bax mRNA expression, respectively, and a 2.17-fold increase in bc1-2 mRNA level. In addition, there were 1.58-fold and 2.67-fold increases in the level of GST-n and MRP-1, respectively; however, the changes in MDR-1 and P-gp levels were not statistically significant. Conclusions: Our data demonstrated that exogenous GSH used as hepatinica in the clinic could induce resistance of A549 cells to CDDP by inhibiting apoptosis, elevating cellular GSH levels, inactivating the mitochondria-mediated signaling pathway, and increasingthe expression of GST-n, y-GCS and MRP1 to increase CDDP efflux.

[This corrects the article on p. 1295 in vol. 10, PMID: 29887946.].