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九种癌症相关基因的突变模式与确诊为膀胱癌的吸烟男性患者中PAF的发生情况

Patterns of mutations in nine cancer-related genes and PAF development among smoking male patients diagnosed with bladder cancer.

作者信息

Alshehri Eman, Al-Dogmi Amal M, Al-Hazani Tahani Mohamed Ibrahim, Alwaili Maha Abdulla, Safhi Fatmah Ahmed, Alneghery Lina Mohammed, Jalal Areej Saud, Alanazi Ibtesam Sanad, AlQassim Fatima Abdullah, Alhumaidi Alotaibi Mashael, Al-Qahtani Wedad Saeed

机构信息

Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Department of Biology, College of Science, Jouf University, Sakakah, Saudi Arabia.

出版信息

Tumour Biol. 2023;45(1):1-14. doi: 10.3233/TUB-220032.

DOI:10.3233/TUB-220032
PMID:36806529
Abstract

BACKGROUND

Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery.

METHODS

Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials.

RESULTS

The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3.

CONCLUSION

Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC.

摘要

背景

吸烟是引发膀胱癌(BC)的最常见风险因素之一。本研究旨在评估吸烟对BC吸烟患者和相同诊断的非吸烟患者PAF体征的影响,以确定其与病理特征的关系以及对零复发和疾病相关恢复的预后。

方法

选取两组患者,吸烟者(n = 54)和非吸烟者(n = 62)。两组患者均患有BC。对他们进行9个癌症相关基因的NGS评估,并通过桑格DNA测序和基于苏木精和伊红(H&E)染色的组织病理学检查进行确认。通过酶联免疫吸附测定(ELISA)检测吸烟因素和PAF发展的影响,并通过免疫化学评估BC区域中PAF-R的表现,与对照组(n = 30)进行比较,对照组包括健康参与者,并采用精心设计的统计试验。

结果

多变量评估显示,BC患者(第3组)中与吸烟相关的突变模式显著增加,PAF发展增加(***P<0.001),与BC非吸烟患者(第2组)和对照组(第1组)相比,PAF-R有明显体征。两组中所有确定的生物学变化(增加/减少)都记录在相同位置。第3组患者有3 - 4种不同突变,而第2组患者有1 - 3种不同突变。对照组的30名受访者未发现突变。在9个检测基因中的3个基因,即TP53、PIK3CA和PTEN中发现了最常见的突变,第3组的增加率最高。此外,组织病理学检查显示BC组织中几乎无法识别和异常的特征,即第2组和第3组之间没有实质性的组织病理学变化。

结论

吸烟由于尿路上皮炎症和9个癌症相关基因的突变增加而引发PAF发展。这些是诱发BC的指示因素。

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