2010-2019年甘肃省肿瘤登记地区肺癌发病的流行病学特征分析

背景与目的肺癌是中国发病率最高、疾病负担最重的恶性肿瘤。近年来,肺癌呈高发趋势,严重影响人群健康。本文通过分析甘肃省肿瘤登记地区2019年肺癌发病特征及2010-2019年发病率趋势,为甘肃省肺癌防控策略制定提供参考依据。方法通过分析甘肃省肿瘤登记地区2019年肺癌发病个案,计算发病率、中标发病率、世标发病率等相关指标;采用Joinpoint计算年度变化百分比(annual percent change,APC),进行趋势分析。结果2019年甘肃省共报告肺癌新发病例3757例,占所有新发恶性肿瘤的14.96%,肺癌发病率、中标率、世标率分别为40.52/10万、30.91/10万和25.86/10万,0-74岁累积率、35-64岁截缩率分别为3.23%和40.03/10万。肺癌发病随着年龄增长而上升,在≥40岁组高发,男、女性人群分别在≥75岁组、≥80岁组达到发病高峰。2010-2019年甘肃省肿瘤登记地区肺癌粗发病率总体呈上升趋势,且上升速度较快,APC为5.39%(P<0.05);分别按照性别、城乡进行统计,各人群肺癌发病率均呈上升趋势,男性、女性、城市、农村人群APC分别为4.98%、6.39%、6.26%和4.64%(P均<0.05)。按照年龄组肺癌发病率进行趋势分析,仅≥65岁组人群肺癌发病以年均4.15%的速度上升(P<0.05)。结论2010-2019年甘肃省肿瘤登记地区肺癌发病率呈现逐年上升趋势,不同性别、地区及年龄组人群肺癌发病存在差异,应针对肺癌发病重点人群开展综合防控工作。

MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest and the HGF/MET c-Met pathway

Background: Accumulating evidence demonstrates that microRNAs(miRNAs) play essential roles in tumorigenesis and cancer progression of hepatocellular carcinoma(HCC). Average targets of a miRNA were more than 100. And one miRNA may act in tumor via regulating several targets. The present study aimed to explore more potential targets of miR-449a by proteomics technology and further uncover the role of miR-449a in HCC tumorigenesis.Methods: Technologies such as i TRAQ-based quantitative proteomic were used to investigate the effect of miR-449a on HCC. The expression of c-Met and miR-449a was detected by q RT-PCR in HCC samples.Gain-and loss-of-function experiments were performed to identify the function and potential target of miR-449a in HCC cells.Results: In HCC, miR-449a was significantly downregulated, while c-Met was upregulated concurrently.Quantitative proteomics and luciferase reporter assay identified c-Met as a direct target of miR-449a.Moreover, miR-449a inhibited HCC growth not only by targeting CDK6 but also by suppressing cMet/Ras/Raf/ERK signaling pathway. Furthermore, the inhibition of c-Met expression with a specific siRNA significantly inhibited cells growth and deregulated the ERK pathway in HCC.Conclusion: The tumor suppressor miR-449a suppresses HCC tumorigenesis by repressing the c-Met/ERK pathway.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients

Background: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. Methods: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. Results: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. Conclusions: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.

RBBP4 promotes colon cancer malignant progression via regulating Wnt/β-catenin pathway

BACKGROUND Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis.However,the potential biological function of RBBP4 in colon cancer is still unknown.AIM To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression.METHODS Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines.The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining.The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown.Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells.Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer.The nuclear translocation ofβ-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown.The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/β-catenin activation.The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown.RESULTS We found that RBBP4 was highly expressed in colon cancer cell lines.The 5-ethynyl-2’-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation.RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition.Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis.Mechanistically,the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway.Meanwhile,RBBP4 knockdown suppressed nuclear translocation ofβ-catenin.With Wnt/β-catenin activator,rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION RBBP4 promotes colon cancer development via increasing activity of the Wnt/β-catenin pathway.RBBP4 may serve as a novel therapeutic target in colon cancer.