Normal tissue adjacent to tumor expression profile analysis developed and validated a prognostic model based on Hippo‐related genes in hepatocellular carcinoma

Pan, Qingbo; Qin, Fanbo; Yuan, Hanyu; He, Baoning; Yang, Ni; Zhang, Yitong; Ren, Hong; Zeng, Yi Arial

doi:10.1002/cam4.3890

Cited by 19 publications

(20 citation statements)

References 54 publications

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“…A recent study on histologically normal breast epithelium by Graham K et al suggested that the microenvironment surrounding the tumor is essential for understanding recurrence [ 33 ]. In line with this phenomenon, the NAT molecular profile is reported to show the prognostic significance for recurrence in patients with different cancers including CRC [ 2 , 3 , 4 ], HCC [ 5 ], prostate [ 6 ], oral carcinoma [ 7 ], breast cancer [ 8 ] and head and neck cancer [ 9 ]. Further investigation on CBX8, as well as other dysregulated NAT molecular markers, for prognosis of CRC patients, warrants evaluation for their clinical use.…”

Section: Discussionmentioning

confidence: 90%

“…The 5-year survival rate remains below 65% in developed countries and under 50% in developing countries [ 1 ], mainly due to recurrence and metastasis. Recent studies demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers including CRC [ 2 , 3 , 4 ], HCC [ 5 ], prostate [ 6 ], oral carcinoma [ 7 ], breast cancer [ 8 ] and head and neck cancer [ 9 ]. We believe a better understanding of the molecular profile in NAT is crucial for identifying molecular biomarkers for predicting the prognosis of CRC patients and therapeutic targets to combat recurrence.…”

Section: Introductionmentioning

confidence: 99%

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High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Ng¹,

Li²,

Man³

et al. 2022

Cells

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Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients. Methods: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR. CBX8 protein level in CRC and NAT specimens from 66 patients was determined by immunohistochemistry. CBX8 gene and protein levels were correlated with the patients’ clinicopathological parameters and circulatory immune cell profiles. The association between CBX8 and pluripotency-associated genes was analyzed using the TCGA database. Results: NAT CBX8 gene level positively correlated with TNM stage, tumor invasion, lymph node metastasis and distant metastasis, indicating its association with tumor progression and metastasis. There was no correlation between NAT CBX8 protein level and clinicopathological parameters. Moreover, a high level of CBX8 gene and protein in NAT both correlated with poor DFS and OS. There was an inverse correlation between CBX8 gene level and post-operative platelet counts and platelet to lymphocyte level, suggesting its association with systematic inflammation. Finally, TCGA analysis showed that CBX8 level was correlated with a couple of pluripotency-associated genes, supporting its association with cancer stemness. Conclusions: High NAT CBX8 is a poor prognostic factor for tumor progression and survival in CRC patients.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Ng¹,

Li²,

Man³

et al. 2022

Cells

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“…However, we suggest MINK1 as a novel candidate gene for autism, congenital cataract, epilepsy and osteoporosis. Although we report the first patient with disruption of MINK1 , the gene has already been implicated in a variety of disorders based on cohort studies in humans, in silico models and work on model organisms, including congenital heart disease in humans [ 20 ] and skeletal and neuronal phenotypes in mice [ 21 , 22 ], as well as cancer [ 23 , 24 ], platelet formation [ 25 ], Alzheimer disease [ 26 , 27 ] and arthritis [ 28 ]. As such, it appears that MINK1 is part of a diverse set of biological processes, which is expected as MINK1 is highly expressed in a variety of tissues ( Figure 2 B) and interacts with a diversity of proteins ( Table S3 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-Omic Investigations of a 17–19 Translocation Links MINK1 Disruption to Autism, Epilepsy and Osteoporosis

Eisfeldt

Schuy

Stattin

et al. 2022

IJMS

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Balanced structural variants, such as reciprocal translocations, are sometimes hard to detect with sequencing, especially when the breakpoints are located in repetitive or insufficiently mapped regions of the genome. In such cases, long-range information is required to resolve the rearrangement, identify disrupted genes and, in symptomatic carriers, pinpoint the disease-causing mechanisms. Here, we report an individual with autism, epilepsy and osteoporosis and a de novo balanced reciprocal translocation: t(17;19) (p13;p11). The genomic DNA was analyzed by short-, linked- and long-read genome sequencing, as well as optical mapping. Transcriptional consequences were assessed by transcriptome sequencing of patient-specific neuroepithelial stem cells derived from induced pluripotent stem cells (iPSC). The translocation breakpoints were only detected by long-read sequencing, the first on 17p13, located between exon 1 and exon 2 of MINK1 (Misshapen-like kinase 1), and the second in the chromosome 19 centromere. Functional validation in induced neural cells showed that MINK1 expression was reduced by >50% in the patient’s cells compared to healthy control cells. Furthermore, pathway analysis revealed an enrichment of changed neural pathways in the patient’s cells. Altogether, our multi-omics experiments highlight MINK1 as a candidate monogenic disease gene and show the advantages of long-read genome sequencing in capturing centromeric translocations.

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“…As far as is known, this is the rst study to emphasize lncRNAs in tumor-adjacent tissues. It has been reported that signals detected from tumor-adjacent tissues could build a superior prognosis model and better predict cancer recurrence (22,23) because 40% of these tissues already exhibited aberrant genomic features (24). We hope that analyzing lncRNAs from these tissues can 1) explore the tumor microenvironment where signals from the tumor and surrounding adipose can be better captured; 2) identify the secretions present in tumor-adjacent cells that could be detected in peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

Body mass index-associated lncRNAs and their roles in lung cancer

Fu¹,

Huang

Lin³

et al. 2022

Preprint

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Background: Obesity often increases the risk of cancer and worsens the prognosis. Unlike most types of cancer, obesity and lung cancer displayed a mixed relationship. Several studies concluded that obesity had an inverse impact on incidents of lung cancer and benefited the overall survival, with few underlying mechanisms understood. Obesity-related and adipocytes-derived lncRNAs had been reported to deregulate the cancer-associated pathways. Here we conducted this study to identify the potential BMI-associated lncRNAs and their roles in lung cancer. Methods: We identified the BMI-associated lncRNAs from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) lung study, with additional analyses of their relationship with lung cancer, impact on overall survival, and potential pathways involved. In addition, we carried out the validation in local peripheral blood samples from 4 groups, including healthy, obese, lung cancer patients with obesity, and lung cancer patients with normal BMI. Results: We identified four BMI-associated lncRNAs which potentially impacting tumor progression and cancer survival. MTORC1 and MYC were among the top pathways enriched from these lncRNAs. We further validated that TM4SF19-AS1 showed a significant difference between lung cancer patients with obesity and with normal BMI in peripheral blood. Conclusions: Our findings suggested that BMI-associated lncRNAs could potentially regulate cancer-related pathways and immune response in lung cancer. The lncRNA validated in peripheral blood could serve as biomarkers to monitor cancer progression.

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Normal tissue adjacent to tumor expression profile analysis developed and validated a prognostic model based on Hippo‐related genes in hepatocellular carcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 54 publications

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients

Multi-Omic Investigations of a 17–19 Translocation Links MINK1 Disruption to Autism, Epilepsy and Osteoporosis

Body mass index-associated lncRNAs and their roles in lung cancer

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