Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients

Zhang, Wei; Lin, Liping; Xia, Ligang; Cai, Wanxia; Dai, Weier; Zou, Chang; Li, Yin; Tang, Donge; Xu, Yong; Dai, Yong

doi:10.1186/s12967-021-02939-7

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…To confirm the GSTM2 expression in colon cancer, we first analyzed the GSTM2 protein expression in human colon cancer tissues and normal adjacent tissues using our own proteomic data (n = 8, samples of the same stage were pooled into one sample) ( 23 ). As a result, the expression of GSTM2 protein was significantly lower in cancerous tissues compared to their paired non-tumor tissues ( Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment

Zhang

Shi

Niu³

et al. 2022

Front. Oncol.

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According to a recent report by GLOBOCAN, colorectal cancer is the third most common and second most deadly cancer in 2020. In our previous proteomic study, we found that the expression of GSTM2 in colon tissues was significantly lower than that in para-cancer tissues, and its lower expression was associated with reduced overall survival rate of patients, suggesting that this gene might play a role in the occurrence of colon cancer. As a member of the detoxifying enzyme family, GSTM2 is likely to play an important role in the initiation of tumors. Whereas, the functions of GSTM2 in colon cancer are barely known. In this study, using the RNA-Seq datasets of colon cancer patients from public database (ntumor = 457, nnormal = 41), we confirmed the reduced expression of GSTM2 and its prognostic value in colon cancer. Furthermore, we used our own Chinese cohort (ntumor = 100, nnormal = 72) verified the lower GSTM2 expression in colon cancer, and also its effects on patient prognosis. Subsequently, we uncovered two potential reasons for the lower expression of GSTM2 in colon cancer tissues, including the deep deletion of GSTM2 on genome, and the up-regulation of RAD21 or SP1. Moreover, we disclosed that GSTM2 might be involved in several immune-related pathways in colon cancer, such as chemokine signaling and leukocyte transendothelial migration. Finally, we revealed that the GSTM2 expression was closely related to the immune-related scores of colon cancer and the infiltration ratios of various immune cells, suggesting that GSTM2 might regulate the development of colon cancer by modulating immune microenvironment. In conclusion, we uncovered the prognostic value of GSTM2 based on the public data and our own data, revealed its potential regulatory role in tumor immune microenvironment, and disclosed the probable reasons for its lower expression in colon cancer. The findings of our study provide a potential prognostic biomarker and drug target for clinical diagnosis and treatment of colon cancer.

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Section: Resultsmentioning

confidence: 99%

Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment

Zhang

Shi

Niu³

et al. 2022

Front. Oncol.

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“…However, the role of succinyl-CoA ligase (SUCL), an enzyme that participates in the TCA cycle and provides a substrate for a known PPGL-suppressor SDH, remains unclear. The expression of SUCL subunit beta SUCLG2 was found to be correlated with several tumors ( 49 , 50 ). Eight germline variants in the GTP-binding domain of SUCLG2 were found in 15 patients with sporadic PPGLs.…”

Section: Discussionmentioning

confidence: 96%

Value of Immunohistochemical Expression of Apelin, Succinate Dehydrogenase B, Chromogranin B, Human Epidermal Growth Factor Receptor-2, Contactin 4, and Succinyl-CoA Synthetase Subunit Beta in Differentiating Metastatic From Non-Metastatic Pheochromocytoma and Paraganglioma

et al. 2022

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ObjectiveWe aimed to retrospectively collect pathologically identified pheochromocytoma and paraganglioma (PPGL) tumor tissues from our center and investigate the expression of apelin and succinyl-CoA synthetase subunit beta (SUCLG2), human epidermal growth factor receptor-2 (HER2 or ERBB-2), contactin 4 (CNTN4), chromogranin B (CHGB), and succinate dehydrogenase B (SDHB) in metastatic and non-metastatic PPGLs, for exploring their roles in the diagnosis of metastatic PPGLs.MethodsA total of 369 patients with pathologically and surgically confirmed PPGLs at Xiangya Hospital, Central South University, between June 2010 and June 2020 were retrospectively included. Sixty patients—12 patients with metastatic PPGLs and 48 patients with non-metastatic PPGLs—were selected through propensity score matching (1:4) to reduce the effect of PPGL type, sex, and age. We observed and quantified the expression of apelin, SDHB, CHGB, ERBB-2, CNTN4, and SUCLG2 in paraffin-embedded samples using immunohistochemical staining.ResultsNo significant differences were observed between the metastatic group and non-metastatic group with respect to the expression of CNTN4 and SUCLG2. The expression of apelin, SDHB, CHGB, and ERBB-2 was significantly different between the two groups. The expression of apelin, SDHB, and CHGB was significantly lower in the metastatic group than that in the non-metastatic group (P < 0.001). ERBB-2 expression was significantly higher in the metastatic group than in the non-metastatic group (P = 0.042). Kaplan–Meier analysis revealed that patients with negative expression of apelin, SDHB, and CHGB showed significantly lower metastasis-free survival than those with positive expression. Multivariate Cox analysis revealed that SDHB and CHGB levels were independently associated with metastasis-free survival.ConclusionThe expression levels of apelin, CHGB, SDHB, and ERBB-2 may be predictive biomarkers for the diagnosis of metastatic PPGLs. Patients with negative expression of apelin, CHGB, and SDHB should be subjected to frequent postoperative follow-up procedures

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“…Sample collection was performed as described in our previous articles ( Sato et al, 2011 ; Zhang et al, 2021a ; Zhang et al, 2021b ). Both tumor and normal adjacent tissues were obtained from the colon segment, and normal adjacent colorectal mucosa was collected from 5 cm away from the tumors.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we need the method of multi-omics cross-analysis to study the same patients at distinct molecular levels to understand the functional context of tumors. In the previous studies, we performed a multi-omics investigation of cancerous and para-cancerous tissues of CRC patients, revealing the dysfunctions of mitochondria in CRC patients [( Zhang et al, 2021a ; Zhang et al, 2021b )].…”

Section: Introductionmentioning

confidence: 99%

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Zhang

Wu²,

Gao³

et al. 2022

Front. Cell Dev. Biol.

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Background: The disturbed molecular alterations of nucleus may promote the development of colorectal cancer (CRC). A multi-platform-based analysis of nucleus of CRC patients helps us to better understand the underlying mechanism of CRC and screen out the potential drug targets for clinical treatment. However, such studies on nucleus in human CRC are still lacking.Methods: We collected the cancerous and para-cancerous tissues from eight CRC patients and performed a multiplex analysis of the molecular changes of the nucleus, including structural variations (SVs), DNA methylation, chromatin accessibility, proteome and phosphorproteome.Results: In our study, we revealed a significant molecular change of nucleus of CRC patients using our original proteomic and phosphorylomic datasets. Subsequently, we characterized the molecular alterations of nucleus of CRC patients at multiple dimensionalities, including DNA, mRNA, protein and epigenetic modification. Next, we found that the great molecular changes of nucleus might affect the biological processes named endocytosis and ubiquitin-mediated proteolysis. Besides, we identified DYNC1LI2 and TPR as the potentially hub proteins within the network of nuclear genes in CRC cells. Furthermore, we identified 1905 CRC-specific SVs, and proclaimed 17 CRC-specific SVs were probably associated with the disturbance of immune microenvironment of CRC patients. We also revealed that the SVs of CXCL5, CXCL10 and CXCL11 might be the core SVs among all the immune-relevant SVs. Finally, we identified seven genes as the upstream transcriptional factors potentially regulating the expression of nuclear genes, such as YY1 and JUN, using a multi-omics approach.Conclusion: Here, we characterized the molecular changes of nucleus of CRC patients, disclosed the potentially core nuclear genes within the network, and identified the probable upstream regulator of nucleus. The findings of this study are helpful to understand the pathogenic molecular changes of nucleus in CRC patients and provide a functional context for drug development in future.

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Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients

Cited by 12 publications

References 40 publications

Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment

Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment

Value of Immunohistochemical Expression of Apelin, Succinate Dehydrogenase B, Chromogranin B, Human Epidermal Growth Factor Receptor-2, Contactin 4, and Succinyl-CoA Synthetase Subunit Beta in Differentiating Metastatic From Non-Metastatic Pheochromocytoma and Paraganglioma

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

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