Advances in cancer biology - metastasis最新文献_第2页

Corrigendum to “Niosomes containing enciprazine hydrochloride have been shown to efficiently inhibit the proliferation and induce apoptosis in colorectal cancer cells” [Advan. Cancer Biol. Metastasis 12 (2024) 100128] “含有盐酸恩西哌嗪的Niosomes已被证明能有效抑制结直肠癌细胞的增殖并诱导细胞凋亡”[Advan。癌症医学杂志。转移12 (2024)100128]

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-12-01 DOI: 10.1016/j.adcanc.2025.100156

Hosain Nasirian , Saeedeh TarvijEslami , Hedieh Ghourchian , Marjaneh Ebrahimi , Tohid Piri-Gharaghie , Ghazal Ghajari

引用次数: 0

Repurposing statins in combination therapy for effective ablation of metastatic breast cancer 他汀类药物联合治疗对转移性乳腺癌的有效消融

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-27 DOI: 10.1016/j.adcanc.2025.100166

Rifat Aara , Neeha Sinai Borker , Jyothilakshmi Sajimon , Seemadri Subhadarshini , Snijesh VP , Vidya P. Nimbalkar , Manju Moorthy , Archana P. Thankamony , Athul Krishnan R , Mohit Kumar Jolly , Jyothi S. Prabhu , Radhika Nair

Metastatic breast cancer (mBC) remains an incurable disease with limited treatment options, highlighting the need for novel therapeutic approaches. The eventual development of resistance to commonly used regimens leading to relapse suggested the presence of intrinsically resistant heterogeneous cell populations. Our previous work identified heterogeneous metastatic tumor cell populations with distinct molecular characteristics driven by MACC1 (Metastasis Associated Colon Cancer 1), which is a key driver of metastasis and therapeutic resistance in multiple solid cancers, including breast cancer. We demonstrated that lovastatin (transcriptional inhibitor of MACC1) treatment ablated the metastatic cells through Macc1 downregulation. Building on this foundation, we evaluated the efficacy of lovastatin in lung metastases and elucidated its regulatory pathways in mBC.

Spatial transcriptomics on an Indian breast cancer patient cohort revealed heterogeneous MACC1 expression across tumors, which correlated with aggressive clinical features. Heterogeneous tumor cells [bulk tumor (Bulk), primary tumor (T1), lung-specific metastatic (L1) cells] were characterized from a metastatic murine model, with L1 showing the highest proliferation rate and MACC1 expression. Lovastatin treatment significantly downregulated MACC1 expression in L1 cells resulting in inhibition of key metastatic phenotypes like proliferation and migration, as well as altered cell type-specific gene expression of programmes like EMT and dormancy, with protein–ligand docking simulations with Sp1, indicating a potential transcriptional regulatory mechanism. Finally, we explored the therapeutic efficacy of lovastatin in combination with chemotherapy and demonstrated that lovastatin effectively ablated chemoresistant tumor cells in mBC. The translational implications of this research could identify patient subgroups that may benefit from statin–chemotherapy combinations and support the repurposing of statins as cost-effective adjuvant therapies for mBC.

转移性乳腺癌（mBC）仍然是一种无法治愈的疾病，治疗方案有限，强调需要新的治疗方法。对常用治疗方案的耐药性最终发展导致复发，这表明存在内在耐药的异质细胞群。我们之前的工作发现了由MACC1（转移相关结肠癌1）驱动的具有不同分子特征的异质性转移性肿瘤细胞群，MACC1是包括乳腺癌在内的多种实体癌转移和治疗耐药的关键驱动因素。我们证明洛伐他汀（MACC1转录抑制剂）治疗通过MACC1下调来消融转移细胞。在此基础上，我们评估了洛伐他汀在肺转移中的疗效，并阐明了其在mBC中的调控途径。一项印度乳腺癌患者队列的空间转录组学研究显示，MACC1在肿瘤中的表达存在异质性，这与侵袭性临床特征相关。异质性肿瘤细胞[散装肿瘤（bulk tumor），原发肿瘤（T1），肺特异性转移（L1）细胞]在转移小鼠模型中被表征，L1显示出最高的增殖率和MACC1表达。洛伐他汀治疗显著下调L1细胞中的MACC1表达，导致增殖和迁移等关键转移表型的抑制，以及EMT和休眠等细胞类型特异性基因表达的改变，通过与Sp1的蛋白配体对接模拟，表明潜在的转录调控机制。最后，我们探讨了洛伐他汀联合化疗的治疗效果，并证明洛伐他汀有效地消融了mBC中的化疗耐药肿瘤细胞。这项研究的转化意义可以确定可能受益于他汀类化疗联合的患者亚组，并支持他汀类药物作为成本效益高的mBC辅助治疗的重新用途。

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引用次数: 0

Anticancer efficacy of 2-Hydroxy-4-methoxybenzoic acid through dual regulation of lactate transport via inhibition of MCT-1 and MCT-4 2-羟基-4-甲氧基苯甲酸通过抑制MCT-1和MCT-4双重调节乳酸转运的抗癌作用

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-18 DOI: 10.1016/j.adcanc.2025.100163

Sneha Yadav , Jyoti Singh , Rohit Kumar , Archana Bharti Sonkar , Anurag Kumar , Dharmendra Kumar , Neeraj Kumar Shrivastava , Mohd Nazam Ansari , Abdulaziz S. Saeedan , Sara A. Aldossary , Gaurav Kaithwas

Monocarboxylate transporters (MCTs) play critical role in the progression of mammary gland carcinoma. The unregulated cell growth increased glycolytic phenotype via glycolysis pathway which leads to concomitant synthesis of lactate. Lactate facilitates acidification of tumour microenvironment (TME), metastasis, and immune evasion. Thus, MCTs inhibition has emerged as a novel approach to treat mammary gland carcinoma. Herein, the current study aim to identify and validate small molecule as dual MCT-1 and MCT-4 inhibitor for mammary gland chemoprevention. We performed structure based virtual screening of natural based library (HY-L057L) and outcomes underscore 2-Hydroxy-4-methoxybenzoic acid (HMBA) as potential compound. HMBA demonstrated higher molecular docking score, favourable ADMET profiling and drug-likeness.Moreover, HMBA was examined for its cytotoxicity and apoptotic activity via in-vitro studies on MCF-7 cells. The results showed that HMBA possessed a substantial IC50 value of 4.8 μM and having apoptotic potential. Additionally, we tested its anticancer effects against a 7,12- dimethylbenz[a]anthracene) (DMBA)-induced tumour model in-vivo. Our findings demonstrated that the HMBA effectively corrected the altered histology and morphology. The altered levels of lactate and antioxidant were also restored by HMBA. In addition, HMBA regulate the mitochondrial apoptotic pathway and inhibit the hypoxia and angiogenesis and the lactate exchange transporters proteins, according to the results of the western blotting. The overall findings obtained from in-silico, in-vitro, and in-vivo studies present strong evidence for the pre-clinical effectiveness of HMBA in treating mammary gland carcinoma through dual inhibition of MCT-1 and MCT-4 and may pave the way for more Investigational New Drug (IND) compliance testing.

单羧酸转运蛋白（mct）在乳腺癌的进展中起着关键作用。不受调节的细胞生长通过糖酵解途径增加糖酵解表型，导致伴随的乳酸合成。乳酸促进肿瘤微环境（TME）酸化、转移和免疫逃逸。因此，抑制mct已成为治疗乳腺癌的一种新方法。本研究旨在鉴定和验证小分子作为MCT-1和MCT-4双重抑制剂在乳腺化学预防中的作用。我们对天然基文库（HY-L057L）进行了基于结构的虚拟筛选，结果表明2-羟基-4-甲氧基苯甲酸（HMBA）是潜在的化合物。HMBA表现出较高的分子对接评分、良好的ADMET谱和药物相似性。此外，通过MCF-7细胞的体外研究，研究了HMBA的细胞毒性和凋亡活性。结果表明，HMBA具有4.8 μM的IC50值，并具有凋亡潜能。此外，我们测试了其对7,12-二甲基苯[a]蒽)（DMBA）诱导的肿瘤模型的体内抗癌作用。我们的研究结果表明，HMBA有效地纠正了组织学和形态学的改变。HMBA也恢复了乳酸和抗氧化剂水平的改变。western blotting结果显示，HMBA调节线粒体凋亡通路，抑制缺氧、血管生成和乳酸交换转运蛋白。从计算机、体外和体内研究中获得的总体结果为HMBA通过双重抑制MCT-1和MCT-4治疗乳腺癌的临床前有效性提供了强有力的证据，并可能为更多的研究新药（IND）依从性测试铺平道路。

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引用次数: 0

Enhancing the anticancer effect of NAMPT inhibition by targeting NAPRT in breast cancer cells 通过靶向乳腺癌细胞的NAPRT增强NAMPT抑制的抗癌作用

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-11-13 DOI: 10.1016/j.adcanc.2025.100161

Zahra Gharedaghi , Parichehr Mehrafshar , Soha Mohammadi , Masoumeh Tavakoli-Yaraki , Pegah Golpour , Mitra Nourbakhsh , Nima Taghizadeh

Introduction

Two pathways in the synthesis of NAD, catalyzed by the key enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), support constant survival, growth, and propagation of cancer cells. This study investigated the effect of the NAMPT inhibitor FK866 combined with 2-Hydroxynicotinic Acid (2-HNA), an inhibitor of nicotinate phosphoribosyltransferase (NAPRT), on breast cancer cell survival, apoptosis, and metastasis.

Methods

MCF-7 and MDA-MB-231 breast cancer cells were cultured and treated with FK866, 2-HNA, or their combinations. Cell viability and apoptosis were evaluated using the MTT assay and Annexin V staining. The effect of inhibitors on p21, BAX, and p53 gene expression was assessed after RNA extraction and cDNA synthesis by real-time PCR using gene-specific primers. Cell migration and invasion were investigated using a scratch assay and matrigel penetration, respectively.

Results

The combination of inhibitors showed synergistic and additive effects in reducing cell viability in MCF-7 and MDA-MB-231 cells, respectively. Both inhibitors induced apoptosis and decreased invasion and migration in breast cancer cells; however, co-treatment was more effective than monotherapy. They significantly enhanced pro-apoptotic gene expression of p53, p21, and BAX, with co-treatment showing greater efficacy in both cell lines.

Conclusion

Simultaneous inhibition of NAMPT and NAPRT reduced cell viability, induced apoptosis, and inhibited metastasis of breast cancer cells. Therefore, targeting NAPRT in addition to NAMPT may offer a more effective therapeutic strategy for breast cancer.

NAD的合成有两种途径，由烟酰胺磷酸核糖基转移酶（NAMPT）和烟酸磷酸核糖基转移酶（NAPRT）两种关键酶催化，支持癌细胞的持续存活、生长和繁殖。本研究探讨了NAMPT抑制剂FK866联合烟酸磷酸核糖基转移酶（NAPRT）抑制剂2-羟基烟酸（2-HNA）对乳腺癌细胞存活、凋亡和转移的影响。方法培养smcf -7和MDA-MB-231乳腺癌细胞，用FK866、2-HNA或其组合处理。采用MTT法和Annexin V染色检测细胞活力和凋亡情况。利用基因特异性引物进行RNA提取和cDNA合成，评估抑制剂对p21、BAX和p53基因表达的影响。细胞迁移和侵袭分别采用划痕法和基质渗透法进行研究。结果联合用药对MCF-7细胞和MDA-MB-231细胞的细胞活力分别有增效和累加作用。两种抑制剂均可诱导乳腺癌细胞凋亡并减少其侵袭和迁移；然而，联合治疗比单一治疗更有效。它们显著增强了促凋亡基因p53、p21和BAX的表达，联合治疗在两种细胞系中显示出更大的疗效。结论同时抑制NAMPT和NAPRT可降低乳腺癌细胞活力，诱导细胞凋亡，抑制乳腺癌细胞转移。因此，除了靶向NAMPT外，靶向NAPRT可能为乳腺癌提供更有效的治疗策略。

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引用次数: 0

Hybrid EMT and inflammation: the deadly alliance 混合急救和炎症：致命的联盟

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-29 DOI: 10.1016/j.adcanc.2025.100160

Rohit Gundamaraju , Vidhya Tangeda , Harshini Raja , Chandrashekar Goud , Hima Sree Buddiraju , Vishnu Pulavarthy

Tumors have unbounded components fitted which execute widespread pathophysiologies. It has been noted that tumor associated inflammation attributes to metastatic endpoints making it an aggressive phenotype. The inflammatory cells and system are set to have a cross talk with tumor cells in the microenvironment varying with the cancer. Likewise, EMT process might also trigger inflammation by the cancer cells. On the other hand, hybrid EMT possesses characteristics of both epithelial and mesenchymal nature which are said to possess unique stemness and express therapeutic resistance. A deeper understanding of the immune events in the tumor microenvironment is necessary to gain better understanding. Further, interpreting how cancer cells are attuning to stress and harsh environments is instrumental in learning about the concept of hybrid EMT. The current review focusses on the interrelationship between inflammation and how might aid in the hybrid EMT phenotype or the regulatory inflammatory factors bolstering hybrid EMT.

肿瘤具有无界的组成部分，这些组成部分执行广泛的病理生理。已经注意到，肿瘤相关的炎症归因于转移终点，使其成为一种侵袭性表型。炎症细胞和系统被设置在随癌症变化的微环境中与肿瘤细胞发生串扰。同样，EMT过程也可能引发癌细胞的炎症。另一方面，杂交EMT同时具有上皮和间充质性质，具有独特的干性和治疗抗性。深入了解肿瘤微环境中的免疫事件对于获得更好的理解是必要的。此外，解释癌细胞如何适应压力和恶劣环境有助于了解混合EMT的概念。目前的综述集中在炎症之间的相互关系以及如何帮助混合型EMT表型或调节炎症因子支持混合型EMT。

引用次数: 0

The multifaceted functions of lncRNA PTPRG-AS1 in human cancers: An in-depth investigation through extensive bioinformatic analyses and literature review lncRNA PTPRG-AS1在人类癌症中的多面功能：通过广泛的生物信息学分析和文献综述进行深入研究

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-24 DOI: 10.1016/j.adcanc.2025.100159

Mohsen Ahmadi , Zahra Tajik , Kiana Salmani , Fatemeh Ghadyani , Soudeh Ghafouri-Fard

Long non-coding RNAs (lncRNAs) have important roles in gene regulation and disease pathogenesis. Among them, PTPRG-AS1 (Protein Tyrosine Phosphatase Receptor Type G Antisense RNA 1) has emerged as a potential player in several cancers, particularly breast cancer. This lncRNA has also been found to be over-expressed in nasopharyngeal carcinoma and lung cancer, among other cancers. Moreover, up-regulation of this lncRNA is associated with metastatic potential of gastric cancer, epithelial ovarian cancer, osteosarcoma, hepatocellular carcinoma and triple negative breast cancer. Several microRNAs have been reported as potential interacting molecules with PTPRG-AS1. This article explores the role of PTPRG-AS1 through a literature-based review and bioinformatics analysis, highlighting its molecular mechanisms, expression patterns, and clinical implications. The data summarized in this review may help design of novel anti-cancer therapies, particularly focusing on combating cancer hallmarks, such as stemness and invasion. However, further experimental validation is needed before implementation of these results in the clinical settings.

长链非编码rna （lncRNAs）在基因调控和疾病发病机制中具有重要作用。其中，PTPRG-AS1（蛋白酪氨酸磷酸酶受体G型反义RNA 1）已成为几种癌症，特别是乳腺癌的潜在参与者。这种lncRNA也被发现在鼻咽癌和肺癌等癌症中过度表达。此外，该lncRNA的上调与胃癌、上皮性卵巢癌、骨肉瘤、肝细胞癌和三阴性乳腺癌的转移潜能有关。一些microrna已被报道为可能与PTPRG-AS1相互作用的分子。本文通过文献综述和生物信息学分析探讨了PTPRG-AS1的作用，重点介绍了其分子机制、表达模式和临床意义。本综述总结的数据可能有助于设计新的抗癌疗法，特别是针对癌症特征，如干细胞和侵袭性。然而，在将这些结果应用于临床之前，还需要进一步的实验验证。

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引用次数: 0

The effect of acute and prolonged acidosis on a panel of carcinoma cell lines 急性和长期酸中毒对一组癌细胞系的影响

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-22 DOI: 10.1016/j.adcanc.2025.100157

Maria Dravecka , Claire Wells , Ole Morten Seternes , Jakob Mejlvang

Due to cancer cell metabolism and disorganized tissue structure, the tumour microenvironment is associated with several pathophysiological conditions, including hypoxia, nutrient deprivation, accumulation of waste products, and acidification of the tumour microenvironment (tumour acidosis). Despite the belief that tumour acidosis drives tumorigenesis, it is still unclear how cancer cells respond to acidosis in the absence of other pathophysiological conditions. Here, we investigate how both acute and prolonged acidosis (pH 6.8) affects different epithelial features of a panel of carcinoma cell lines. We find that acute acidosis in all cell lines investigated represses cell growth and causes a disturbance of adherens junctions and apical-basal polarity, reminiscent of epithelial-to-mesenchymal transition (EMT). However, these changes did not coincide with altered expression of E− and N-cadherin. Neither did acute acidosis have a general effect on adhesion and migration in our panel of cell lines. Exposing our panel of carcinoma cell lines to acidosis for more than six weeks did not lead to adaptations restoring cell growth. On the contrary, prolonged acidosis caused one cell line (A431) to halt proliferation. Another cell line (A549) reacted to prolonged acidosis by gradually inducing the expression of ZEB2, which in turn orchestrated cadherin switching, possibly indicating a gradual induction of EMT. In the rest of the cell lines, we did not find any noticeable effect of prolonged acidosis. Lastly, all cell lines quickly restored their original phenotype and growth rate when returned to media with normal pH (pH 7.5). Collectively, our findings reveal that carcinoma cells exposed to moderate acidosis (pH 6.8) generally exhibit slower proliferation rates and a reduction in apical-basal polarity. Furthermore, we conclude that prolonged exposure to acidic conditions, depending on the specific cell line, may elicit responses that could influence tumour progression and the efficacy of cancer treatments.

由于癌细胞代谢和组织结构紊乱，肿瘤微环境与多种病理生理条件相关，包括缺氧、营养剥夺、废物积累和肿瘤微环境酸化（肿瘤酸中毒）。尽管认为肿瘤酸中毒驱动肿瘤发生，但在没有其他病理生理条件的情况下，癌细胞如何对酸中毒作出反应尚不清楚。在这里，我们研究了急性和长期酸中毒（pH值6.8）如何影响一组癌细胞系的不同上皮特征。我们发现，在所有被研究的细胞系中，急性酸中毒抑制细胞生长，并引起粘附连接和顶基极性的干扰，使人想起上皮到间充质转化（EMT）。然而，这些变化与E -和n -钙粘蛋白表达的改变并不一致。急性酸中毒对我们的细胞系的粘附和迁移也没有普遍的影响。将我们的癌细胞组暴露在酸中毒中超过六周并没有导致细胞恢复生长的适应性。相反，长时间的酸中毒导致一个细胞系（A431）停止增殖。另一种细胞系（A549）通过逐渐诱导ZEB2的表达来应对长时间的酸中毒，ZEB2反过来又协调钙粘蛋白的转换，可能表明逐渐诱导EMT。在其余的细胞系中，我们没有发现任何明显的长时间酸中毒的影响。最后，当返回正常pH （pH 7.5）培养基时，所有细胞系迅速恢复其原始表型和生长速度。总的来说，我们的研究结果表明，暴露于中度酸中毒（pH 6.8）的癌细胞通常表现出较慢的增殖速率和根尖极性的降低。此外，我们得出结论，长期暴露于酸性条件下，取决于特定的细胞系，可能引发可能影响肿瘤进展和癌症治疗效果的反应。

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引用次数: 0

Temozolomide resistance in glioblastoma: a non-coding RNA viewpoint 替莫唑胺在胶质母细胞瘤中的耐药性：非编码RNA的观点

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-22 DOI: 10.1016/j.adcanc.2025.100158

Maryam Motallebinezhad , Ali Faravash , Mohammad Ghasemian , Zahra Tajik , Mohsen Ahmadi , Solat Eslami , Soudeh Ghafouri-Fard

As an imidazotetrazine derived from the alkylating substance dacarbazine, Temozolomide (TMZ) is commonly used as the routine chemotherapy for new cases of glioblastoma multiforme (GBM). It substantially improves the clinical outcome of patients. But, resistance to TMZ is regarded as a principal impediment in the postgenomic years of GBM management. Recent investigations showed the critical roles of lncRNAs, miRNAs and circRNAs and their interactions in GBM treatment. Remarkably, several miRNAs, such as miR-125b, miR-30b-3p, miR-24-3p, miR-590, miR-125b, and miR-7-5p regulate activity of glioma stem cells. Besides, a number of miRNAs, namely miR-370-3p, miR-198, miR-486-3p, miR-29c, miR-130a, miR-181 d, miR-198, miR-182-5p and miR-370-3p regulate expression of the DNA repair protein MGMT. Most of lncRNAs and circRNAs exert their role on TMZ resistance through sponging miRNAs. Notably, these transcripts have revolutionized the understanding about GBM pathogenesis and application of personalized medicine for this cancer. This review concentrates on the importance of these transcripts in resistance to TMZ in GBM patients.

替莫唑胺（Temozolomide， TMZ）是一种由烷基化物质达卡巴嗪衍生的咪唑四嗪，是新发多形性胶质母细胞瘤（GBM）常用的常规化疗药物。它大大改善了患者的临床结果。但是，对TMZ的抵抗被认为是GBM管理后基因组年的主要障碍。最近的研究表明lncrna、mirna和circrna及其相互作用在GBM治疗中的关键作用。值得注意的是，几种mirna，如miR-125b、miR-30b-3p、miR-24-3p、miR-590、miR-125b和miR-7-5p调节胶质瘤干细胞的活性。此外，miR-370-3p、miR-198、miR-486-3p、miR-29c、miR-130a、miR-181 d、miR-198、miR-182-5p和miR-370-3p等多种mirna可调节DNA修复蛋白MGMT的表达。大多数lncrna和circrna通过海绵mirna在TMZ耐药中发挥作用。值得注意的是，这些转录本已经彻底改变了对GBM发病机制的理解和针对这种癌症的个性化医疗的应用。这篇综述集中在这些转录物在GBM患者对TMZ耐药中的重要性。

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引用次数: 0

Integrated dysregulation of RNF43 and associated lncRNAs reveals transcriptional remodeling in colorectal carcinoma RNF43和相关lncrna的综合失调揭示了结直肠癌的转录重塑

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-10-03 DOI: 10.1016/j.adcanc.2025.100155

Alireza Soleimani , Amir Sadeghi , Zahra Fazeli , Solat Eslami , Mohammad Rahmanian , Binazir Khanabadi , Soudeh Ghafouri-Fard , Mir Davood Omrani

The Wnt signaling cascade is crucial for diverse biological processes, including cell cycle regulation, inflammation, embryonic development, and tumorigenesis. The present study investigates the expression of TSPOAP1-AS1, TMEM147-AS1, and FOXP4-AS1 lncRNAs, along with RNF43, all of which are associated with the Wnt/β-catenin signaling pathway, in colorectal cancer (CRC) samples compared to adjacent normal tissues (ANTs). RNF43 was significantly overexpressed in CRC samples, with a median 2.34-fold increase relative to normal tissues (P value = 0.04). In contrast, the lncRNA TSPOAP1-AS1 was markedly down-regulated in tumors, showing a median 0.42-fold reduction (P value = 0.03). The remaining two lncRNAs—TMEM147-AS1 and FOXP4-AS1—were also significantly elevated, exhibiting median fold-changes of 2.94-fold (P value < 0.0001) and 2.02-fold (P value = 0.003), respectively. All four transcripts achieved exceptionally high specificity (97.5–100 %) but only moderate sensitivity (29.3–56.1 %) for discrimination of CRC samples from ANTS, reflecting their stringent discrimination of ANTs at the expense of missing a subset of tumors. Taken together, our results revealed a coordinated dysregulation of Wnt-related genes in CRC, i.e. loss of TSPOAP1-AS1 alongside gain of RNF43, TMEM147-AS1, and FOXP4-AS1 expression, highlighting their potential as complementary biomarkers.

Wnt信号级联对多种生物过程至关重要，包括细胞周期调节、炎症、胚胎发育和肿瘤发生。本研究研究了TSPOAP1-AS1、TMEM147-AS1、FOXP4-AS1 lncRNAs以及RNF43在结直肠癌（CRC）样本中的表达，这些lncRNAs均与Wnt/β-catenin信号通路相关。RNF43在结直肠癌样本中显著过表达，相对于正常组织中位数增加2.34倍（P值= 0.04）。相比之下，lncRNA TSPOAP1-AS1在肿瘤中明显下调，中位数降低0.42倍（P值= 0.03）。其余两个lncrna - tmem147 - as1和foxp4 - as1也显著升高，中位倍数变化分别为2.94倍（P值<； 0.0001）和2.02倍（P值= 0.003）。所有四种转录本都具有异常高的特异性（97.5 - 100%），但在从ANTS中区分CRC样本方面仅具有中等敏感性（29.3 - 56.1%），这反映了它们以遗漏肿瘤子集为代价严格区分ANTS。综上所述，我们的研究结果揭示了CRC中wnt相关基因的协同失调，即TSPOAP1-AS1的缺失与RNF43、TMEM147-AS1和FOXP4-AS1表达的增加，突出了它们作为互补生物标志物的潜力。

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引用次数: 0

TMEM119 and NRXN2 as prognostic biomarkers for liver metastasis in gastric cancer TMEM119和NRXN2作为胃癌肝转移的预后生物标志物

IF 3 Q3 ONCOLOGY

Advances in cancer biology - metastasis

Pub Date : 2025-09-26 DOI: 10.1016/j.adcanc.2025.100154

Yunfan Wang , Ke Min , Jun Shi , Jun Jin , Qiang Yao , Jianping Zhou , Weimin Wang

Background

Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis.

Methods

We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients.

Results

The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort.

Conclusion

TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.

胃癌（GC）是一种常见的消化道恶性肿瘤，死亡率高，主要是由于肝转移。驱动这一过程的潜在分子机制仍然知之甚少。本研究旨在寻找胃癌肝转移的新型预后生物标志物。方法分析来自癌症基因组图谱（TCGA）数据库的非转移性、肝转移性和其他转移性胃癌患者样本的mRNA表达数据。采用加权基因共表达网络分析（Weighted gene共表达network analysis， WGCNA）鉴定与肝转移相关的关键基因模块和枢纽基因。根据差异表达、Kaplan-Meier生存分析确定的预后价值和单变量Cox回归模型进行风险评估，筛选潜在的生物标志物。研究结果随后在380例胃癌患者的独立队列中得到验证。结果WGCNA鉴定出一个与胃癌肝转移相关的基因模块（MEgrey）。在该模块中，TMEM119和NRXN2被鉴定为关键枢纽基因，其在肝转移组中的表达明显高于非转移组和其他转移组。TMEM119或NRXN2的高表达与较短的总生存期（OS）相关，并表明死亡风险增加（HR > 1）。这些发现在我们的验证队列中得到了证实。结论tmem119和NRXN2是预测胃癌患者肝转移的有希望的预后生物标志物，可能成为潜在的治疗靶点。

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引用次数: 0