Epidemiological evidence remains conflicting regarding diet and risk of lung cancer. We sought to systematically investigate whether dietary factors are associated with the risk of incident lung cancer in the UK Biobank. A total of 416,588 participants (54% women) from the UK Biobank were included in the present study. Based on baseline data from FFQs, 3 main dietary patterns were identified by using principal component analysis. Cox proportional hazards models were used to investigate the association of individual food groups and dietary patterns with lung cancer risk. During a median follow-up of 7.13 y, 1782 incident lung cancer cases were documented. The association analysis showed high intake of red meat and processed meat was associated with an increased risk of lung cancer (HR_{per 50 g/d}: 1.36; 95% CI: 1.13, 1.65 for red meat; HR_{per 25 g/d}: 1.30; 95% CI: 1.10, 1.53 for processed meat). However, the consumption of fruits (HR_{per 100 g/d}: 0.90; 95% CI: 0.84, 0.95), vegetables (HR_{per 100 g/d}: 0.89; 95% CI: 0.81, 0.99), breakfast cereals (HR_{per 50 g/d}: 0.81; 95% CI: 0.74, 0.89), and dietary fiber (HR_{per 5 g/d}: 0.76; 95% CI: 0.69, 0.84) was inversely associated with the risk of lung cancer. For the dietary pattern analysis [quartile (Q) comparison], high adherence to the Prudent pattern (HR_{Q4 compared with Q1}: 0.84; 95% CI: 0.73, 0.96) was associated with a lower risk of lung cancer, whereas the Western pattern (HR_{Q4 compared with Q1}: 1.27; 95% CI: 1.11, 1.46) was associated with a higher risk of lung cancer. Our study indicated that a diet characterized by high intake of fruits, vegetables, breakfast cereals, and dietary fiber, as well as low intake of red meat and processed meat, was associated with a lower risk of lung cancer.

To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer. We included 469 691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable-adjusted hazard ratios (HRs) for lung cancer (2177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia, and snoring) and examined the interaction and joint effects with a lung cancer polygenic risk score. A U-shaped association was observed for sleep duration and lung cancer risk, with an 18% higher risk (95% confidence interval [CI]: 1.07 to 1.30) for short sleepers and a 17% higher risk (95% CI: 1.02 to 1.34) for long sleepers compared with normal sleepers (7–8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95% CI: 1.07 to 1.46), but no association was found for insomnia or snoring. Compared with participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HR_{sleep duration}: 1.83; 95% CI: 1.47 to 2.27; HR_chronotype: 1.85; 95% CI: 1.34 to 2.56). Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with poor prognosis. Cancer-testis genes (CTGs) have been vigorously pursued as targets for cancer immunotherapy, but the expressive patterns and functional roles of CTGs remain unclear in ESCC. A systematic screening strategy was adopted to screen CTGs in ESCC by integrating multiple public databases and RNA expression microarray data from 119 ESCC subjects. For the newly identified ESCC prognosis-associated CTGs, an independent cohort of 118 patients with ESCC was recruited to validate the relationship via immunohistochemistry. Furthermore, functional assays were performed to determine the underlying mechanisms. 21 genes were recognized as CTGs, in particular, CDCA5 was aberrantly upregulated in ESCC tissues and significantly associated with poor prognosis (HR = 1.85, 95%CI: 1.14-3.01, P = .013). Immunohistochemical staining confirmed that positive CDCA5 expression was associated with advanced TNM staging and a shorter overall survival rate (45.59% vs 28.00% for CDCA5-/+ subjects, P = 1.86 × 10-3). H3K27 acetylation in CDCA5 promoter might lead to the activation of CDCA5 during ESCC tumorigenesis. Functionally, in vitro assay of gain- and loss-of-function of CDCA5 suggested that CDCA5 could promote ESCC cells proliferation, invasion, migration, apoptosis resistance and reduce chemosensitivity to cisplatin. Moreover, in vivo assay showed that silenced CDCA5 could inhibit tumor growth. Mechanistically, CDCA5 knockdown led to an arrest in G2/M phase and changes in the expression of factors that played fundamental roles in the cell cycle pathway. CDCA5 contributed to ESCC progression and might serve as an attractive target for ESCC immunotherapy. FUND: This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20181083 and BK20181496), Jiangsu Top Expert Program in Six Professions (No. WSW-003 and WSW-007), Major Program of Science and Technology Foundation of Jiangsu Province (No. BE2016790 and BE2018746), Jiangsu Medical Young Talent Project (No. QNRC2016566), the Program of Jiangsu Medical Innovation Team (No. CXTDA2017006), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1487) and Jiangsu Province 333 Talents Project (No. BRA2017545).

Copy number variations (CNVs) represent one of the most common genomic alterations. This study aimed to evaluate the roles of genes within highly aberrant genome regions in the prognosis of esophageal squamous cell cancer (ESCC). Exome sequencing data from 81 paired ESCC tissues were used to screen aberrant genomic regions. The associations between CNVs and gene expression were evaluated using gene expression data from the same individuals. Then, an RNA expression array profile from 119 ESCC samples was adopted for differential gene expression and prognostic analyses. Two independent ESCC cohorts with 315 subjects were further recruited to validate the prognostic value using immunohistochemistry tests. Finally, we explored the potential mechanism of our identified novel oncogene in ESCC. In total, 2003 genes with CNVs were observed, of which 76 genes showed recurrent CNVs in more than three samples. Among them, 32 genes were aberrantly expressed in ESCC tumor tissues and statistically correlated with CNVs. Strikingly, 4 (CTTN, SHANK2, INPPL1 and ANO1) of the 32 genes were significantly associated with the prognosis of ESCC patients. Patients with a positive expression of ANO1 had a poorer prognosis than ANO1 negative patients (overall survival rate: 42.91% versus 26.22% for ANO1−/+ samples, P < 0.001). Functionally, ANO1 promoted ESCC cell proliferation, migration and invasion by activating transforming growth factor-β pathway. Knockdown of ANO1 significantly inhibited tumor progression in vitro and in vivo. In conclusion, ANO1 is a novel oncogene in ESCC and may serve as a prognostic biomarker for ESCC.

Objective. By observing the needle‐knife of KOA rabbit morphology, knee joint cartilage p‐FAK, p‐PI3K, Aggrecan gene, and protein expression, to study the effect of needle‐knife to promote cartilage cell synthesis metabolism mechanism. Method. 49 male New Zealand rabbits, randomly divided into normal group (Z), model group (M), model‐inhibitors (MP), needle‐knife group (D), needle‐knife inhibitors group (DP), electroacupuncture group (E), and electroacupuncture inhibitors (EP). RT‐PCR and Western Blot were used to test each animal cartilage p‐FAK, p‐PI3K, and Aggrecan gene and protein expression level. Results. Compared with N group, p‐FAK and p‐PI3K protein and mRNA expression of M group, D group, and E group increased (P < 0.05), while the protein and mRNA expression of Aggrecan reduced (P < 0.05). Compared with M group, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA of E and D group increased (P < 0.05). Compared with E group, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA expression of D group increased (P < 0.05); after adding inhibitors, p‐FAK, p‐PI3K, Aggrecan protein, and mRNA expression reduced (P < 0.05). Conclusion. Needle‐knife therapy can promote the repairment of cartilage cells by activating FAK‐PI3K signaling pathways, promoting the synthesis of cartilage cell metabolism.