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骨桥蛋白(SPP1)在结直肠癌中的预后价值需要个性化分子方法。

Prognostic value of Osteopontin (SPP1) in colorectal carcinoma requires a personalized molecular approach.

作者信息

Assidi Mourad, Gomaa Wafaey, Jafri Mohammad, Hanbazazh Mehenaz, Al-Ahwal Mahmoud, Pushparaj Peter, Al-Harbi Asia, Al-Qahtani Mohammed, Buhmeida Abdelbaset, Al-Maghrabi Jaudah

机构信息

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.

Medical Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Tumour Biol. 2019 Sep;41(9):1010428319863627. doi: 10.1177/1010428319863627.

Abstract

Stratification of colorectal cancer for better management and tangible clinical outcomes is lacking in clinical practice. To reach this goal, the identification of reliable biomarker(s) is a prerequisite to deliver personalized colorectal cancer theranostics. Osteopontin (SPP1) is a key extracellular matrix protein involved in several pathophysiological processes including cancer progression and metastasis. However, the exact molecular mechanisms regulating its expression, localization, and molecular functions in cancer are still poorly understood. This study was designed to investigate the SPP1 expression profiles in Saudi colorectal cancer patients, and to assess its prognostic value. Hundred thirty-four (134) archival paraffin blocks of colorectal cancer were collected from King Abdulaziz University Hospital, Saudi Arabia. Tissue microarrays were constructed, and automated immunohistochemistry was performed to evaluate SPP1 protein expression patterns in colorectal cancer. About 20% and 23% of our colorectal cancer samples showed high SPP1 cytoplasmic and nuclear expression patterns, respectively. Cytoplasmic SPP1 did not correlate with age, gender, tumor size, and location. However, significant correlations were observed with tumor grade ( = 0.008), tumor invasion ( = 0.01), and distant metastasis ( = 0.04). Kaplan-Meier survival analysis showed a significantly lower recurrence rate in patients with higher SPP1 cytoplasmic expression ( = 0.05). At multivariate analysis, high SPP1 cytoplasmic expression was an independent favorable prognostic marker ( = 0.02). However, nuclear SPP1 expression did not show any prognostic value ( = 0.712). Our results showed a particular SPP1 prognostic relevance that is not in line with most colorectal cancer previous studies that may be attributed to the molecular pathophysiology of our colorectal cancer cohort. Saudi Arabia has both specific genomic makeup and particular environment that could lead to distinctive molecular roots of cancer. SPP1 has several isoforms, tissue localizations and molecular functions, signaling pathways, and downstream molecular functions. Therefore, a more individualized approach for CRC studies and particularly SPP1 prognosis outcomes' assessment is highly recommended toward precision oncology.

摘要

在临床实践中,缺乏对结直肠癌进行分层以实现更好的管理和切实的临床结果。为实现这一目标,识别可靠的生物标志物是实现个性化结直肠癌诊疗的先决条件。骨桥蛋白(SPP1)是一种关键的细胞外基质蛋白,参与包括癌症进展和转移在内的多种病理生理过程。然而,调节其在癌症中的表达、定位和分子功能的确切分子机制仍知之甚少。本研究旨在调查沙特结直肠癌患者的SPP1表达谱,并评估其预后价值。从沙特阿拉伯阿卜杜勒阿齐兹国王大学医院收集了134块结直肠癌存档石蜡块。构建组织微阵列,并进行自动免疫组织化学以评估结直肠癌中SPP1蛋白的表达模式。我们的结直肠癌样本中分别约有20%和23%显示出高SPP1细胞质和细胞核表达模式。细胞质SPP1与年龄、性别、肿瘤大小和位置无关。然而,与肿瘤分级(=0.008)、肿瘤侵袭(=0.01)和远处转移(=0.04)存在显著相关性。Kaplan-Meier生存分析显示,SPP1细胞质表达较高的患者复发率显著较低(=0.05)。在多变量分析中,高SPP1细胞质表达是一个独立的良好预后标志物(=0.02)。然而,细胞核SPP1表达未显示任何预后价值(=0.712)。我们的结果显示了一种特殊的SPP1预后相关性,这与大多数先前的结直肠癌研究不一致,这可能归因于我们结直肠癌队列的分子病理生理学。沙特阿拉伯具有特定的基因组构成和特殊环境,这可能导致癌症独特的分子根源。SPP1有几种异构体、组织定位和分子功能、信号通路以及下游分子功能。因此,强烈建议采用更个性化的方法进行结直肠癌研究,尤其是SPP1预后结果评估,以实现精准肿瘤学。

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