Background: Cancer remains a major cause of mortality and a significant economic burden in China. Exploring the disparities in cancer patterns and control strategies between China and developed countries may offer valuable insights for policy formulation and enhance cancer management efforts. This study examined the incidence, mortality, and disability‐adjusted life year (DALY) burden of cancer in China, and compared these metrics with those observed in the United States (US) and the United Kingdom (UK). Methods: Data on cancer incidence, mortality, and DALYs for China, the US, and the UK were sourced from the GLOBOCAN 2022 online database and the Global Burden of Disease 2021 study (GBD 2021). We utilized Joinpoint regression models to analyze trends in cancer incidence and mortality across these countries, calculating annual percent changes (APCs) and determining the optimal joinpoints. Results: In 2022, China recorded around 4,824,703 new cancer cases and 2,574,176 cancer‐related deaths, contributing to 71,037,170 DALYs. China exhibited a lower cancer incidence rate compared to the US and the UK. Although cancer‐related mortality in China is slightly lower than that in the UK, it is significantly higher than that in the US. Additionally, China experienced significantly higher DALY rates compared to both the US and UK. The cancer landscape in China was also undergoing significant changes, with a rapid rise in the incidence and burden of lung, colorectal, breast, cervical, and prostate cancers. Meanwhile, the incidence and burden of stomach cancer continued to decline. Although the incidence of liver and esophageal cancers was decreasing, the burden of liver cancer was increasing, while the burden of esophageal cancer remained largely unchanged. Conclusions: The cancer profile of China is shifting from that of a developing country to one more typical of a developed country. The ongoing population aging and the rise in unhealthy lifestyles are expected to further escalate the cancer burden in China. Consequently, it is crucial for Chinese authorities to revise the national cancer control program, drawing on successful strategies from developed countries, while also accounting for the regional diversity in cancer types across China.

Objective: Adopting a healthy lifestyle, including regular physical activity, is widely believed to decrease cancer risk. This study aimed to quantitatively establish the dose‐response relationships between total physical activity and the risk of breast, colon, lung, gastric, and liver cancers. Methods: A systematic review and dose‐response analysis were conducted using PubMed and Embase from January 1, 1980 to March 20, 2023. Prospective cohort studies that examined the association between physical activity and the risks of any of the 5 outcomes were included. The search was confined to publications in the English language with a specific focus on human studies. Physical activity is standardized by using the data from US National Health and Nutrition Examination Surveys (NHANES) and the Global Burden of Disease 2019 database. Results: A total of 98 studies, involving a combined population of 16,418,361 individuals, were included in the analysis. Among the included studies, 57 focused on breast cancer, 17 on lung cancer, 23 on colon cancer, 5 on gastric cancer, and 7 on liver cancer. Overall, elevated levels of physical activity exhibited an inverse correlation with the risk of cancer. The dose‐response curve for lung cancer exhibited a non‐linear pattern, with the greatest benefit risk reduction observed at 13,200 MET‐minutes/week of physical activity, resulting in a 14.7% reduction in risk (relative risk 0.853, uncertainty interval 0.798 to 0.912) compared to the inactive population. In contrast, the dose‐response curves for colon, gastric, breast, and liver cancers showed linear associations, indicating that heightened levels of total physical activity were consistently associated with reduced cancer risks. However, the increase in physical activity yielded a smaller risk reduction for colon and gastric cancers compared to breast and liver cancers. Compared to individuals with insufficient activity (total activity level < 600 MET‐minutes/week), individuals with high levels of activity (≥ 8,000 MET‐minutes/week) experienced a 10.3% (0.897, 0.860 to 0.934) risk reduction for breast cancer; 5.9% (0.941, 0.884 to 1.001) for lung cancer; 7.1% (0.929, 0.909 to 0.949) for colon cancer; 5.1% (0.949, 0.908 to 0.992) for gastric cancer; 17.1% (0.829, 0.760 to 0.903) for liver cancer. Conclusions: This study demonstrated a significant inverse relationship between total physical activity and the risk of breast, gastric, liver, colon, and lung cancers.

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Background: Lung adenocarcinoma (LUAD) is the most prevalent histotype of non‐small cell lung cancer. Anoikis, an alternative form of programmed cell death, plays a pivotal role in cancer invasion and metastasis, preventing the detached cancer cells from readhering to other substrates for abnormal proliferation. The aim of this study was to conduct a comprehensive analyses of the prognostic implications of anoikis‐related genes (ARGs) in LUAD.Methods: ARGs were selected from The Cancer Genome Atlas (TCGA) database and Genecards dataset using differential expression analysis. The signature incorporating ARGs was identified using univariate Cox regression analysis and LASSO regression analysis. Furthermore, a nomogram containing the signature and clinical information was developed through univariate and multivariate Cox regression analysis. Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curves were applied to evaluate the predictive validity of these risk models. Finally, functional analysis of the selected ARGs in signature and analysis of immune landscape were also conducted.Results: A 16‐gene signature was integrated to stratify LUAD patients into different survival risk groups. The prognostic risk score generated from the signature and TNM stage were identified as independent prognostic factors and utilized to develop a nomogram. Both the signature and the nomogram showed satisfactory prediction performance in predicting overall survival (OS) of LUAD patients. The ARGs were enriched in several biological functions and signaling pathways. Finally, differences of immune landscape were investigated among the high‐ and low‐risk groups stratified by the signature.Conclusions: This study revealed potential relationships between ARGs and prognosis of LUAD. The prognostic predictors identified in present study could be utilized as potential biomarkers for clinical applications.

(1) Background: Several randomized controlled trials (RCTs) have been conducted in combination with Efficacy and Safety of Epidermal Growth Factor Receptor(EGFR)-Tyrosine Kinase Inhibitor (TKI) for the first-line treatment of patients with advanced non-small cell lung cancer; however, head-to-head comparisons of combination therapies are still lacking. Therefore, this study aims to compare the efficacy and safety of various combination treatments. (2) Methods: We conducted a systematic review and Bayesian network meta-analysis by searching MEDLINE, EMBASE, and COCHRANE for relevant RCTs. (3) Results: TKI combined with antiangiogenic therapy, chemotherapy, or radiation achieved a significant benefit compared with TKI alone for progression free survival (PFS). A combination with radiation yielded better benefits in PFS than any other treatment. In terms of overall survival (OS), only the combination with pemetrexed and carboplatin (HR = 0.63, 95% credible interval 0.43–0.86)/radiation (0.44, 0.23–0.83) was superior to TKI alone. All of the combination therapies may increase the incidence of ≥Grade 3 AEs, as the pooled RRs are over 1; different toxicity spectrums were revealed for individual treatments. (4) Conclusions: The TKI combination of radiation/pemetrexed and carboplatin could provide the best antitumor effects among the first generation TKI-based treatments. Considering safety, ramucirumab and bevacizumab may be the ideal additions to TKIs (systematic review registration: PROSPERO CRD42022350474).

Microbes play a significant role in human tumor development and profoundly impact treatment efficacy, particularly in immunotherapy. The respiratory tract extensively interacts with the external environment and possesses a mucosal immune system. This prompts consideration of the relationship between respiratory microbiota and lung cancer. Advancements in culture‐independent techniques have revealed unique communities within the lower respiratory tract. Here, we provide an overview of the respiratory microbiota composition, dysbiosis characteristics in lung cancer patients, and microbiota profiles within lung cancer. We delve into how the lung microbiota contributes to lung cancer onset and progression through direct functions, sustained immune activation, and immunosuppressive mechanisms. Furthermore, we emphasize the clinical utility of respiratory microbiota in prognosis and treatment optimization for lung cancer.