Whole-exome sequencing of rectal cancer identifies locally recurrent mutations in the Wnt pathway

Yang, Yi; Gu, Xiaodong; Li, Zhenyang; Zheng, Chuang; Wang, Zihao; Zhou, Meng; Chen, Zongyou; Li, Mengzhen; Li, Dongbing; Xiang, Jianbin

doi:10.18632/aging.203618

Cited by 10 publications

(2 citation statements)

References 51 publications

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“…The hypermethylation of SOX14 is related to cervical cancer, and SOX14 has the potential to be a molecular biological marker for cervical cancer screening and early diagnosis [13] . The transcriptional and translational expression levels of the SOX17 gene connected with the Wnt signaling pathway are higher in rectal cancer (READ) tissues than in normal rectal tissues, which may provide a basis for predicting the local recurrence of READ and development of novel therapeutic agents [14] .…”

Section: Discussionmentioning

confidence: 99%

Analysis of SOX gene family expression and prognostic significance in lung adenocarcinoma based on tumor databases

Chen

et al. 2023

Preprint

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Objective To analyze the expression of the SOX gene family in lung adenocarcinoma and its impact on the prognosis of lung adenocarcinoma patients using tumor databases. Methods The cBioPortal database was used to retrieve and analyze the mutation frequencies and variants of 10 genes in the SOX gene family in lung adenocarcinoma tissues. Using clinical information from the Kaplan-Meier plotter database, the potential prognostic values of 10 genes in the SOX gene family in lung adenocarcinoma patients were further explored. The UALCAN database and TCGA database were used to obtain the expression of methylation of SOX gene family members and compare the mRNA expression of 10 genes in lung adenocarcinoma tissues and paracancerous tissues, respectively. The miRCancer database was intersected with miRTarBase, ENCORI, and miRWalk databases to find the lung adenocarcinoma-related miRNAs that regulate the SOX gene family. Results Most members in the SOX gene family had expansion mutation, but SOX15 had a deletion mutation. The expressions of SOX8 and SOX17 genes were upregulated in lung adenocarcinoma patients (HR < 1, log-rank P < 0.05), which was beneficial to their prognosis. In addition, SOX3, SOX5, SOX6, SO12, SOX14, SOX15, SOX18 and SRY genes were all significantly downregulated in lung adenocarcinoma patients (HR > 1, log-rank P < 0.05), suggesting that their high expression was associated with poor prognosis. The expressions of SOX5, SOX6, SOX12, SOX17, SOX18 and SRY in lung adenocarcinoma tissues were lower than those in paraneoplastic tissues (P < 0.05). The mRNA expression of the SOX15 gene in lung adenocarcinoma tissues was significantly higher than that in paracancerous tissues (P < 0.05). Moreover, SOX3, SOX5, SOX8, SOX14, SOX17 and SOX18 showed hypermethylation, while SOX15 and SRY showed hypomethylation in lung adenocarcinoma tissues, and the difference was statistically significant (P < 0.05). The low expressions of SOX5, SOX17, and SOX18 were correlated with their promoter region hypermethylation, suggesting that their methylation may also play a role in the occurrence and development of lung adenocarcinoma. Furthermore, hsa-miR-1-3p and miR-499a-5p were positively correlated with SOX5 (r = 0.272, p = 3.87x10− 10) and SOX6 (r = 0.109, p = 1.34x10− 2), respectively. Conclusion The SOX gene family is closely implicated in the onset and progression of lung adenocarcinoma, of which most members can be used as prognostic marker genes for tumor patients.

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Section: Discussionmentioning

confidence: 99%

Analysis of SOX gene family expression and prognostic significance in lung adenocarcinoma based on tumor databases

Chen

et al. 2023

Preprint

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“…The expression of proteins was detected using immunohistochemistry ( 17 ). The DAKO EnVision system was used for immunoperoxidase staining.…”

Section: Methodsmentioning

confidence: 99%

Whole-genome sequencing identified novel mutations in a Chinese family with lynch syndrome

Dong²,

Shen³

et al. 2023

Front. Oncol.

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BackgroundLynch syndrome (LS) is caused by a germline mutation in one of the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. The definition of Lynch syndrome is based on clinical, pathological, and genetic findings. Therefore, the identification of susceptibility genes is essential for accurate risk assessment and tailored screening programs in LS monitoring.Patients and methodsIn this study, LS was diagnosed clinically in a Chinese family using Amsterdam II criteria. To further explore the molecular characteristics of this LS family, we performed whole genome sequencing (WGS) to 16 members in this family and summarized the unique mutational profiles within this family. We also used Sanger sequencing technology and immunohistochemistry (IHC) to verify some of the mutations identified in the WGS analysis.ResultsWe showed that mutations in mismatch repair (MMR) related genes, as well as pathways including DNA replication, base excision repair, nucleotide excision repair, and homologous recombination were enhanced in this family. Two specific variants, MSH2 (p.S860X) and FSHR (p.I265V) were identified in all five members with LS phenotypes in this family. The MSH2 (p.S860X) variant is the first reported variant in a Chinese LS family. This mutation would result in a truncated protein. Theoretically, these patients might benefit from PD-1 (Programmed death 1) immune checkpoint blockade therapy. The patients who received nivolumab in combination with docetaxel treatments are currently in good health.ConclusionOur findings extend the mutation spectrum of genes associated with LS in MLH2 and FSHR, which is essential for future screening and genetic diagnosis of LS.

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Emerging roles and biomarker potential of WNT6 in human cancers

Ferreira,

Gonçalves,

Costa

2024

Cell Commun Signal

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The WNT6 ligand is a well-known activator of the WNT signaling pathway, considered a vital player in several important physiologic processes during embryonic development and maintaining homeostasis throughout life, regulating the proliferation and differentiation of multiple stem/progenitor cell types. More recently, as it is the case for many key molecular regulators of embryonic development, dysregulation of WNT6 has been implicated in cancer development and progression in multiple studies. In this review, we overview the most significant recent findings regarding WNT6 in the context of human malignancies, exploring its influence on multiple dimensions of tumor pathophysiology and highlighting the putative underlying WNT6-associated molecular mechanisms. We also discuss the potential clinical implications of WNT6 as a prognostic and therapeutic biomarker. This critical review highlights the emerging relevance of WNT6 in multiple human cancers, and its potential as a clinically-useful biomarker, addressing key unanswered questions that could lead to new opportunities in patient diagnosis, stratification, and the development of rationally-designed precision therapies.

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Whole-exome sequencing of rectal cancer identifies locally recurrent mutations in the Wnt pathway

Cited by 10 publications

References 51 publications

Analysis of SOX gene family expression and prognostic significance in lung adenocarcinoma based on tumor databases

Analysis of SOX gene family expression and prognostic significance in lung adenocarcinoma based on tumor databases

Whole-genome sequencing identified novel mutations in a Chinese family with lynch syndrome

Emerging roles and biomarker potential of WNT6 in human cancers

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