Evaluating the Quality of Cancer-Related WeChat Public Accounts: Cross-Sectional Study.

BACKGROUND: WeChat (Tencent) is one of the most important information sources for Chinese people. Relevantly, various health-related data are constantly transmitted among WeChat users. WeChat public accounts (WPAs) for health are rapidly emerging. Health-related WeChat public accounts have a significant impact on public health. Because of the rise in web-based health-seeking behavior, the general public has grown accustomed to obtaining cancer information from WPAs. Although WPAs make it easy for people to obtain health information, the quality of the information is questionable. OBJECTIVE: This study aims to assess the quality and suitability of cancer-related WeChat public accounts (CWPAs). METHODS: The survey was conducted from February 1 to 28, 2023. Based on the WPA monthly list provided by Qingbo Big Data, 28 CWPAs in the WeChat communication index were selected as the survey sample. Quality assessment of the included CWPAs was performed using the HONcode instrument. Furthermore, suitability was measured by using the Suitability Assessment of Materials. A total of 2 researchers conducted the evaluations independently. RESULTS: Of the 28 CWPAs, 12 (43%) were academic and 16 (57%) were commercial. No statistical difference was found regarding the HONcode scores between the 2 groups (P=.96). The quality of the academic and commercial CWPAs evaluated using the HONcode instrument demonstrated mean scores of 5.58 (SD 2.02) and 5.63 (SD 2.16), respectively, corresponding to a moderate class. All CWPAs' compliance with the HONcode principles was unsatisfactory. A statistically significant difference between the 2 groups was observed in the Suitability Assessment of Materials scores (P=.04). The commercial WPAs reached an overall 55.1% (SD 5.5%) score versus the 50.2% (SD 6.4%) score reached by academic WPAs. The suitability of academic and commercial CWPAs was considered adequate. CONCLUSIONS: This study revealed that CWPAs are not sufficiently credible. WPA owners must endeavor to create reliable health websites using approved tools such as the HONcode criteria. However, it is necessary to educate the public about the evaluation tools of health websites to assess their credibility before using the provided content. In addition, improving readability will allow the public to read and understand the content.

Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer.

Background: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.

Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma.

BACKGROUND: Besides featured glucose consumption, recent studies reveal that cancer cells might prefer "addicting" specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. METHODS: Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of LINC01614 into exosomes were identified using flow cytometric sorting, fluorescence in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 in lung adenocarcinoma (LUAD) and CAFs were investigated using 4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were performed to investigate the underlying mechanisms involved. RESULTS: We demonstrate that cancer-associated fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived exosomes, mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-κB, which leads to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. CONCLUSION: Our study highlights the therapeutic potential of targeting a CAF-specific lncRNA to inhibit glutamine utilization and cancer progression in LUAD.

Predicting Tumor Mutation Burden and EGFR Mutation Using Clinical and Radiomic Features in Patients with Malignant Pulmonary Nodules.

Pulmonary nodules (PNs) shown as persistent or growing ground-glass opacities (GGOs) are usually lung adenocarcinomas or their preinvasive lesions. Tumor mutation burden (TMB) and somatic mutations are important determinants for the choice of strategy in patients with lung cancer during therapy. A total of 93 post-operative patients with 108 malignant PNs were enrolled for analysis (75 cases in the training cohort and 33 cases in the validation cohort). Radiomics features were extracted from preoperative non-contrast computed tomography (CT) images of the entire tumor. Using commercial next generation sequencing, we detected TMB status and somatic mutations of all FFPE samples. Here, 870 quantitative radiomics features were extracted from the segmentations of PNs, and pathological and clinical characteristics were collected from medical records. The LASSO (least absolute shrinkage and selection operator) regression and stepwise logistic regressions were performed to establish the predictive model. For the epidermal growth factor receptor (EGFR) mutation, the AUCs of the clinical model and the integrative model validated by the validation set were 0.6726 (0.4755-0.8697) and 0.7421 (0.5698-0.9144). For the TMB status, the ROCs showed that AUCs of the clinical model and the integrative model validated by the validation set were 0.7808 (0.6231-0.9384) and 0.8462 (0.7132-0.9791). The quantitative radiomics signatures showed potential value in predicting the EGFR mutant and TMB status in GGOs. Moreover, the integrative model provided sufficient information for the selection of therapy and deserves further analysis.

LncRNA LINC00525 suppresses p21 expression via mRNA decay and triplex-mediated changes in chromatin structure in lung adenocarcinoma.

BACKGROUND: Emerging evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various cancers. In the present study, we aim to investigate the function and molecular mechanism of an up-regulated and survival-associated lncRNA, LINC00525, in lung adenocarcinoma (LUAD). METHODS: The expression level of LINC00525 in tissues was determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH). The functional role of LINC00525 in LUAD was investigated using gain-and loss-of-function approaches, both in vivo and in vitro. RNA pull-down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), triplex-capture assay, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were used to investigate the potential underlying mechanisms involved. RESULTS: LINC00525 is highly expressed in LUAD cells and tissues. Survival analysis indicated that upregulation of LINC00525 was associated with poor prognosis in patients with LUAD patients. Knockdown of LINC00525 inhibited cell proliferation and cell cycle progression in vitro. In xenograft models, LINC00525 knockdown suppressed tumor growth and tumorigenesis of tumor-bearing mice. Mechanistically, LINC00525 epigenetically suppressed p21 transcription by guiding Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) to the p21 promoter through an formation of RNA-DNA triplex with the p21 promoter, leading to increased trimethylation of lysine 27 on histone 3 (H3K27me3) of the p21 promoter. In addition, LINC00525 repressed p21 expression post-transcriptionally by enhancing p21 mRNA decay. LINC00525 promoted p21 mRNA decay by competitively binding to RNA Binding Motif Single Stranded Interacting Protein 2 (RBMS2). CONCLUSION: Our findings demonstrate that LINC00525 promotes the progression of LUAD by reducing the transcription and stability of p21 mRNA in concert with EZH2 and RBMS2, thus suggesting that LINC00525 may be a potential therapeutic target for clinical intervention in LUAD.