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1.
Commun Biol ; 7(1): 860, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003419

RESUMO

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.


Assuntos
Adenocarcinoma de Pulmão , Predisposição Genética para Doença , Neoplasias Pulmonares , Locos de Características Quantitativas , Humanos , Adenocarcinoma de Pulmão/genética , China/epidemiologia , População do Leste Asiático/genética , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/genética , Poliadenilação , Polimorfismo de Nucleotídeo Único
2.
J Proteomics ; 305: 105247, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38950696

RESUMO

The aim of this study was to explore potential novel plasma protein biomarkers for lung adenocarcinoma (LUAD). A plasma proteomics analysis was carried out and candidate protein biomarkers were validated in 102 LUAD cases and 102 matched healthy controls. The same LUAD tumor tissues were detected to explore the correlation between the expression of candidate proteins in tissues and plasma and vascular normalization. A LUAD active metastasis mice model was constructed to explore the role of candidate proteins for lung metastasis. GPI and PGD were verified to be upregulated in plasma from LUAD patients, and the expression of GPI in tumor tissue was positively correlated with the expression of GPI in plasma and negatively correlated with the normalization of tumor blood vessels. Meanwhile, a negative correlation between the expression of GPI and PGD in plasma and tumor vascular normalization was discovered. In the LUAD active metastasis model, the lowest levels of vascular normalization and the highest expression of GPI and PGD were found in mice with lung metastases. This study found that GPI and PGD may be potential plasma biomarkers for LUAD, and monitoring those may infer the risk of metastasis and malignancy of the tumor. SIGNIFICANT: We identified GPI and PGD as potential novel diagnostic and prognostic biomarkers for LUAD. PGD and GPI can be used as diagnostic biomarkers in combination with other available strategies to assist in the screening and diagnosis of LUAD, and as prognostic biomarkers aid in predict the risk of tumor metastasis and malignancy in patients with LUAD.


Assuntos
Adenocarcinoma de Pulmão , Biomarcadores Tumorais , Neoplasias Pulmonares , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Biomarcadores Tumorais/sangue , Glicosilfosfatidilinositóis/metabolismo , Glicosilfosfatidilinositóis/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Multiômica , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/metabolismo , Prognóstico , Proteômica/métodos , Idoso
3.
Int J Surg ; 110(2): 1052-1067, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016140

RESUMO

BACKGROUND: This study aimed to elucidate the consistency of differentially expressed hub mRNAs and proteins in lung adenocarcinoma (LUAD) across populations and to construct a comprehensive LUAD prognostic signature. METHODS: The transcriptomic and proteomics data from different populations were standardized and analyzed using the same criteria to identify the consistently differential expressed mRNAs and proteins across genders and races. We then integrated prognosis-related mRNAs with clinical, pathological, and EGFR (epidermal growth factor receptor) mutation data to construct a survival model, subsequently validating it across populations. Through plasma proteomics, plasma proteins that consistently differential expressed with LUAD tissues were screened and validated, with their associations discerned by measuring expressions in tumor tissues and tumor vascular normalization. RESULTS: The consistency rate of differentially expressed mRNAs and proteins was ~20-40%, with ethnic factors leading to about 40-60% consistency of differentially expressed mRNA or protein across populations. The survival model based on the identified eight hub mRNAs as well as stage, smoking status, and EGFR mutations, demonstrated good prognostic prediction capabilities in both Western and East Asian populations, with a higher number of unfavorable variables indicating poorer LUAD prognosis. Notably, GPI expression in tumor tissues was inversely correlated with vascular normalization and positively correlated with plasma GPI expression. CONCLUSION: Our study underscores the significance of integrating transcriptomics and proteomics data, emphasizing the need to account for genetic diversity among ethnic groups. The developed survival model may offer a holistic perspective on LUAD progression, enhancing prognosis and therapeutic strategies.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética
4.
Environ Res ; 245: 118056, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157958

RESUMO

A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adolescente , Adulto Jovem , Humanos , Fumar/epidemiologia , Fumar Tabaco , Eletrônica
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