Machine learning-driven discovery of anoikis-related biomarkers in Adult T-Cell Leukemia/Lymphoma subtypes

Mohadeseh Zarei Ghobadi, Elaheh Afsaneh
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Abstract

Adult T-Cell Leukemia/Lymphoma (ATLL) is a malignancy that arises from T-cells infected with the human T-cell lymphotropic virus type 1 (HTLV-1). The disease is characterized by uncontrolled proliferation and reduced apoptosis of malignant T cells, which contributes to tumor progression and resistance to therapy. Anoikis is a specific form of programmed cell death triggered by the loss of cell–matrix or cell–cell adhesion, playing a critical role in preventing detached cells from surviving and forming tumors. Dysregulation of anoikis has been implicated in cancer metastasis and therapeutic resistance across various malignancies; however, its role in ATLL remains largely unexplored. To our knowledge, this is the first study to investigate anoikis-related genes in ATLL subtypes, particularly across its major subtypes: acute, chronic, and smoldering. In this study, we explored anoikis-related differentially expressed genes to identify those specifically associated with each subtype. We then applied Least Absolute Shrinkage and Selection Operator (LASSO) regression to select the most informative features. Subsequently, we employed decision trees, random forest, extreme gradient boosting, support vector machine, and logistic regression algorithms to identify classifier genes distinguishing each ATLL subtype from asymptomatic carriers. The identified biomarkers include SMARCE1 and CASP3 for acute, TGFΒ1 and MTA1 for chronic, and CXCL1 and LGALS8 for smoldering subtypes. These genes are involved in cell adhesion, survival signaling, and apoptosis—key processes in cellular homeostasis and oncogenesis. Our findings provide novel insights into the molecular mechanisms linking anoikis to ATLL subtypes and highlight potential therapeutic targets.
成人t细胞白血病/淋巴瘤亚型中嗜酸相关生物标志物的机器学习驱动发现
成人t细胞白血病/淋巴瘤(ATLL)是一种由t细胞感染人类t细胞嗜淋巴病毒1型(HTLV-1)引起的恶性肿瘤。该疾病的特点是恶性T细胞增殖不受控制和凋亡减少,这有助于肿瘤进展和对治疗的抵抗。Anoikis是一种特定形式的程序性细胞死亡,由细胞-基质或细胞-细胞粘附丧失引发,在阻止分离细胞存活和形成肿瘤中起关键作用。anoikis的失调与各种恶性肿瘤的癌症转移和治疗耐药性有关;然而,它在ATLL中的作用在很大程度上仍未被探索。据我们所知,这是第一个研究ATLL亚型中嗜酒相关基因的研究,特别是在其主要亚型中:急性、慢性和闷烧。在这项研究中,我们探索了与嗜酒症相关的差异表达基因,以确定与每种亚型特异性相关的基因。然后,我们应用最小绝对收缩和选择算子(LASSO)回归来选择信息量最大的特征。随后,我们采用决策树、随机森林、极端梯度增强、支持向量机和逻辑回归算法来识别区分ATLL亚型和无症状携带者的分类器基因。已确定的生物标志物包括急性型的SMARCE1和CASP3,慢性型的TGFΒ1和MTA1,阴燃亚型的CXCL1和LGALS8。这些基因参与细胞粘附、生存信号和细胞凋亡——细胞稳态和肿瘤发生的关键过程。我们的发现为将anoikis与ATLL亚型联系起来的分子机制提供了新的见解,并突出了潜在的治疗靶点。
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来源期刊
Advances in biomarker sciences and technology
Advances in biomarker sciences and technology Biotechnology, Clinical Biochemistry, Molecular Medicine, Public Health and Health Policy
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