Screening and identification of biomarkers associated with the diagnosis and prognosis of lung adenocarcinoma

Wang, Yanyun; Zhang, Lin; Chen, Yitong; Li, Man; Ha, Minwen; Li, Songbai

doi:10.1002/jcla.23450

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…The other published finding concerning breast cancer is that the somatic SEMA6D mutations that were predicted to cause loss of gene function were identified in early onset breast cancers [ 51 ], a cancer type that is typically aggressive, frequently triple-negative, and associated with poor outcomes; this result, again, is potentially compatible with our finding that lower SEMA6D expression was associated with poorer outcomes. Some support is also available from other cancers; for example, in lung cancer, which is also invariably treated with cytotoxic chemotherapy, somatic SEMA6D mutations were found that reduced SEMA6D expression, and low SEMA6D expression was associated with poor outcomes [ 52 ]. In terms of mechanisms, it is challenging to speculate since it has not even been determined in these cells whether SEMA6D is working as a ligand for plexins, or as a receptor in its own right, therefore a multitude of potential down-stream signaling pathways exist [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

Baxter

Allinson

Amri

et al. 2021

Cancers

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Background: poor prognosis primary breast cancers are typically treated with cytotoxic chemotherapy. However, recurrences remain relatively common even after this aggressive therapy. Comparison of matched tumours pre- and post-chemotherapy can allow identification of molecular characteristics of therapy resistance and thereby potentially aid discovery of novel predictive markers or targets for chemosensitisation. Through this comparison, we aimed to identify microRNAs associated with chemoresistance, define microRNA target genes, and assess targets as predictors of chemotherapy response. Methods: cancer cells were laser microdissected from matched breast cancer tissues pre- and post-chemotherapy from estrogen receptor positive/HER2 negative breast cancers showing partial responses to epirubicin/cyclophosphamide chemotherapy (n = 5). MicroRNA expression was profiled using qPCR arrays. MicroRNA/mRNA expression was manipulated in estrogen receptor positive/HER2 negative breast cancer cell lines (MCF7 and MDA-MB-175 cells) with mimics, inhibitors or siRNAs, and chemoresponse was assessed using MTT and colony forming survival assays. MicroRNA targets were identified by RNA-sequencing of microRNA mimic pull-downs, and comparison of these with mRNAs containing predicted microRNA binding sites. Survival correlations were tested using the METABRIC expression dataset (n = 1979). Results: miR-195 and miR-26b were consistently up-regulated after therapy, and changes in their expression in cell lines caused significant differences in chemotherapy sensitivity, in accordance with up-regulation driving resistance. SEMA6D was defined and confirmed as a target of the microRNAs. Reduced SEMA6D expression was significantly associated with chemoresistance, in accordance with SEMA6D being a down-stream effector of the microRNAs. Finally, low SEMA6D expression in breast cancers was significantly associated with poor survival after chemotherapy, but not after other therapies. Conclusions: microRNAs and their targets influence chemoresponse, allowing the identification of SEMA6D as a predictive marker for chemotherapy response that could be used to direct therapy or as a target in chemosensitisation strategies.

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Section: Discussionmentioning

confidence: 99%

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

Baxter

Allinson

Amri

et al. 2021

Cancers

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“…BUB1, BUB1B, PLK1, and CDC20 were suggested as LUAD stem cell biomarkers (60). CENPF, KIF2C, CDK1, ASPM, and MYH10 were also proposed as diagnosis and prognosis biomarkers of LUAD (61)(62)(63)(64)(65)(66). CDKN3 was not yet reported as a diagnosis or prognosis biomarker but expected to be a promising therapeutic target in LUAD (63).…”

Section: Discussionmentioning

confidence: 99%

A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma

et al. 2021

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Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.

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“… 12 On the other hand, in lung adenocarcinoma, SEMA6D expression was downregulated, and lower SEMA6D levels were associated with shorter overall survival indicating a tumor suppressor role in the lung. 13 Altogether, the data suggest a context-dependent role for SEMA6D in tumorigenesis.…”

Section: Introductionmentioning

confidence: 83%

SEMA6D Differentially Regulates Proliferation, Migration, and Invasion of Breast Cell Lines

et al. 2022

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Semaphorin 6D (SEMA6D), a member of the class 6 semaphorin family, is a membrane-associated protein that plays a key role in the development of cardiac and neural tissues. A growing body of evidence suggests that SEMA6D is also involved in tumorigenesis. In breast cancer, high SEMA6D levels are correlated with better survival rates. However, very little is known about the functional significance of SEMA6D in breast tumorigenesis. In the present study, we aimed to investigate the effects of SEMA6D expression on the normal breast cell line MCF10A and the breast cancer cell lines MCF7 and MDA MB 231. We demonstrated that SEMA6D expression increases the proliferation of MCF10A cells, whereas the opposite effect was observed in MCF7 cells. SEMA6D expression induced anchorage-independent growth in both cancer cell lines. Furthermore, migration of MCF10A and MCF7 cells and invasion of MDA MB 231 cells were elevated in response to SEMA6D overexpression. Accordingly, the genes related to epithelial-mesenchymal transition (EMT) were altered by SEMA6D expression in MCF10A and MCF7 cell lines. Finally, we provided evidence that SEMA6D levels were associated with the expression of the cell cycle, EMT, and Notch signaling pathway-related genes in breast cancer patients’ data. We showed for the first time that SEMA6D overexpression has cell-specific effects on the proliferation, migration, and invasion of normal and cancer breast cell lines, which agrees with the gene expression data of clinical samples. This study lays the groundwork for future research into understanding the functional importance of SEMA6D in breast cancer.

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Screening and identification of biomarkers associated with the diagnosis and prognosis of lung adenocarcinoma

Cited by 13 publications

References 30 publications

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

MiR-195 and Its Target SEMA6D Regulate Chemoresponse in Breast Cancer

A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma

SEMA6D Differentially Regulates Proliferation, Migration, and Invasion of Breast Cell Lines

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