High expression of RAD21 predicts poor survival in patients with operated non-small-cell lung cancer

Zhu, Tao; Gao, Zhaojia; Yuan, Kai; Wang, Yong

doi:10.1177/0300891620910805

Cited by 8 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, It has also been proven that the higher RAD21 expression in tumor tissues is associated with shorter DSS of patients with colorectal cancer. Also, the higher expression of RAD21 in patients promotes the resistance of chemoradiotherapy and chemotherapy (36). All in all, our results are consistent with the previous studies, and the function of RAD21 in colon cancer further indicates that GSTM2 may be involved in tumor formation as a suppressor.…”

Section: Discussionsupporting

confidence: 92%

“…RAD21 encodes a subunit of cohesin, and mainly involved in modifying the adhesion and separation of sister chromatids, thus regulating gene transcription and DNA damage repairing. Numerous studies have revealed that RAD21 is over expressed in a variety of tumors, such as colorectal cancer, non small cell lung cancer, and breast cancer (35)(36)(37). Besides, It has also been proven that the higher RAD21 expression in tumor tissues is associated with shorter DSS of patients with colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

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.

View full text Add to dashboard Cite

show abstract

“…We also investigated the prognostic impact of RAD21 alterations. Previously, it was reported that RAD21 overexpression is a marker for poor prognosis in breast [ 48 – 50 ], bladder [ 51 ], KRAS mutant colorectal carcinomas [ 52 ], and NSCLC [ 53 ]. Our results are in line with this finding, where patients with RAD21 altered breast invasive ductal carcinoma had significantly worse median overall survival compared to their WT counterparts.…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer landscape of telomeric content shows that RAD21 and HGF alterations are associated with longer telomeres

Sharaf¹,

Montesion²,

Hopkins³

et al. 2022

Genome Med

View full text Add to dashboard Cite

Background Cancer cells can proliferate indefinitely through telomere maintenance mechanisms. These mechanisms include telomerase-dependent elongation, mediated by TERT activation, and alternative lengthening of telomeres (ALT), linked to loss of ATRX or DAXX. Methods We analyzed the telomeric content of 89,959 tumor samples within the Foundation Medicine dataset and investigated the genomic determinants of high telomeric content, linking them to clinical outcomes, when available. Results Telomeric content varied widely by disease type with leiomyosarcoma having the highest and Merkel cell carcinoma having the lowest telomeric content. In agreement with previous studies, telomeric content was significantly higher in samples with alterations in TERC, ATRX, and DAXX. We further identified that amplifications in two genes, RAD21 and HGF, were enriched in samples with high telomeric content, which was confirmed using the PCAWG/ICGC dataset. We identified the minimal amplified region associated with high telomeric content for RAD21 (8q23.1–8q24.12), which excludes MYC, and for HGF (7q21.11). Our results demonstrated that RAD21 and HGF exerted an additive telomere lengthening effect on samples with existing alterations in canonical genes previously associated with telomere elongation. Furthermore, patients with breast cancer who harbor RAD21 alterations had poor median overall survival and trended towards higher levels of Ki-67 staining. Conclusions This study highlights the importance of the role played by RAD21 (8q23.1–8q24.12) and HGF (7q21.11) in the lengthening of telomeres, supporting unlimited replication in tumors. These findings open avenues for work aimed at targeting this crucial pathway in tumorigenesis.

show abstract

“…RAD21 expression in colorectal cancer cells was modulated by Wnt/β-catenin activation and was associated with shorter disease-specific survival in patients with KRAS mutant tumors ( 11 , 25 ). Furthermore, high RAD21 expression conferred poor survival in patients with non-small cell lung cancer, especially in stages II–III ( 26 ). However, the correlation between RAD21 and ovarian cancer prognosis has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

RAD21 Confers Poor Prognosis and Affects Ovarian Cancer Sensitivity to Poly(ADP-Ribose)Polymerase Inhibitors Through DNA Damage Repair

Gou

Dong

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundPoly(ADP-ribose)polymerase (PARP) inhibitors are a class of molecular-targeted cancer drugs. Synthetic lethality is a phenomenon that renders homologous recombination repair defective cells more sensitive to PARP inhibitors. As a component of the cohesin complex, RAD21 regulates DNA damage repair. However, the biological roles of RAD21 in ovarian cancer and their underlying mechanisms remain unclear.MethodsAn immunohistochemical assay was used to validate the expression of RAD21 in ovarian cancer and its correlation with prognosis. The effects of RAD21 were evaluated through Cell Counting Kit-8 (CCK8), wound-healing, and invasion assays in vitro and the tumor growth in vivo. Furthermore, CCK8 assay and immunofluorescence assay were used to detect the effect of RAD21 on cell sensitivity to PARP inhibitors and their mechanism. The pathway changes were detected by Western blotting.ResultsRAD21 was markedly upregulated in ovarian cancer samples. High RAD21 expression was correlated with poor differentiation and poor prognosis in patients with ovarian cancer. Functionally, RAD21 overexpression promoted cancer cell proliferation, migration, and invasion. Moreover, RAD21 knockdown increased the sensitivity of ovarian cancer cells to three kinds of PARP inhibitors by affecting DNA damage repair. In vivo experiments indicated that RAD21 promoted tumor growth. Mechanistically, the overexpression of RAD21 led to increased phosphorylation levels of Akt and mTOR. Blocking the Akt/mTOR signaling pathway reversed RAD21 overexpression-induced cancer progression and drug resistance.ConclusionsRAD21 can serve as a valuable prognostic marker for ovarian cancer and has the potential as a therapeutic target that can expand the utility of PARP inhibitors.

show abstract

High expression of RAD21 predicts poor survival in patients with operated non-small-cell lung cancer

Cited by 8 publications

References 19 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

A pan-cancer landscape of telomeric content shows that RAD21 and HGF alterations are associated with longer telomeres

RAD21 Confers Poor Prognosis and Affects Ovarian Cancer Sensitivity to Poly(ADP-Ribose)Polymerase Inhibitors Through DNA Damage Repair

Contact Info

Product

Resources

About