BreathMAT Lab, Pakistan Institute of Nuclear Science and Technology (PINSTEC), Islamabad 44000, Pakistan.
Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Molecules. 2022 Apr 30;27(9):2857. doi: 10.3390/molecules27092857.
A gastric cancer (GC) diagnosis relies on histopathology. Endoscopy rates are increasing. infection is a major GC risk factor. In an effort to elucidate abundant blood biomarkers, and potentially reduce the number of diagnostic surgical interventions, we investigated sera and biopsies from a cohort of 219 positive and negative patients diagnosed with GC, gastritis, and ulcers. This allowed the comparative investigation of the different gastroduodenal diseases, and the exclusion of protein changes resulting from bacterial infection or inflammation of the gastric mucosa when searching for GC-dependent proteins.
High-definition mass spectrometry-based expression analysis of tryptically digested proteins was performed, followed by multivariate statistical and network analyses for the different disease groups, with respect to infection status. Significantly regulated proteins differing more than two-fold between groups were shortlisted, and their role in gastritis and GC discussed.
We present data of comparative protein analyses of biopsies and sera from patients suffering from mild to advanced gastritis, ulcers, and early to advanced GC, in conjunction with a wealth of metadata, clinical information, histopathological evaluation, and infection status. We used samples from pre-malignant stages to extract prospective serum markers for early-stage GC, and present a 29-protein marker panel containing, amongst others, integrin β-6 and glutathione peroxidase. Furthermore, ten serum markers specific for advanced GC, independent of infection, are provided. They include CRP, protein S100A9, and kallistatin. The majority of these proteins were previously discussed in the context of cancer or GC. In addition, we detected hypoalbuminemia and increased fibrinogen serum levels in gastritis.
Two protein panels were suggested for the development of multiplex tests for GC serum diagnostics. For most of the elements contained in these panels, individual commercial tests are available. Thus, we envision the design of multi-protein assays, incorporating several to all of the panel members, in order to gain a level of specificity that cannot be achieved by testing a single protein alone. As their development and validation will take time, gastritis diagnosis based on the fibrinogen to albumin serum ratio may be a quick way forward. Its determination at the primary/secondary care level for early diagnosis could significantly reduce the number of referrals to endoscopy. Preventive measures are in high demand. The protein marker panels presented in this work will contribute to improved GC diagnostics, once they have been transferred from a research result to a practical tool.
胃癌（GC）的诊断依赖于组织病理学。内窥镜检查的比例正在增加。感染是 GC 的一个主要危险因素。为了阐明丰富的血液生物标志物，并可能减少诊断性手术干预的数量，我们调查了 219 名阳性和阴性 GC、胃炎和溃疡患者的血清和活检。这使得对不同的胃十二指肠疾病进行了比较性研究，并在寻找 GC 相关蛋白时排除了细菌感染或胃黏膜炎症引起的蛋白变化。
采用基于高清质谱的胰蛋白酶消化蛋白表达分析，对不同疾病组进行多元统计和网络分析，同时考虑感染状态。对组间差异大于两倍的显著调节蛋白进行了筛选，并讨论了它们在胃炎和 GC 中的作用。
我们提供了轻度至重度胃炎、溃疡和早期至晚期 GC 患者活检和血清的比较蛋白质分析数据，以及大量的元数据、临床信息、组织病理学评估和感染状态。我们使用来自癌前阶段的样本提取早期 GC 的前瞻性血清标志物，并提供了包含整合素β-6 和谷胱甘肽过氧化物酶在内的 29 种蛋白标志物面板。此外，还提供了 10 种与感染无关的针对晚期 GC 的血清标志物。其中包括 CRP、蛋白 S100A9 和卡利斯塔丁。这些蛋白中的大多数以前在癌症或 GC 的背景下讨论过。此外，我们还检测到胃炎患者的血清白蛋白水平降低和纤维蛋白原水平升高。
提出了两个用于开发 GC 血清诊断的多重测试的蛋白面板。这些面板中包含的大多数元素都有单独的商业测试。因此，我们设想设计多蛋白检测，将多个或全部面板成员纳入其中，以获得仅测试单个蛋白无法达到的特异性水平。由于其开发和验证需要时间，因此基于纤维蛋白原与白蛋白血清比值的胃炎诊断可能是一种快速的前进方式。它在初级/二级保健水平上的确定可以为早期诊断显著减少内镜检查的转诊数量。预防措施的需求很高。本工作中提出的蛋白标志物面板将有助于提高 GC 的诊断，一旦它们从研究结果转化为实用工具。
