Expression, clinical significance and correlation of RUNX3 and HER2 in colorectal cancer

Yu-rong, WU; Xue, Jun; Li, Yuanrui; Wu, Xueliang; Qu, Ming; Xu, Deping; Shi, Yongquan

doi:10.21037/jgo-21-403

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…Investigations in colorectal cancer confirmed that a decline in RUNX3 expression correlates with increased cell proliferation and invasion [ 94 ]. This was further corroborated by Wu et al, who detected a marked downregulation of RUNX3 in colorectal cancer, concomitant with an inverse correlation with HER2 expression [ 95 ]. Cumulatively, these findings underscore RUNX3's predominant function as a tumor suppressor, consistently found to be downregulated in diverse cancer types.…”

Section: Runx Proteins In the Landscape Of Cancer Expressionsupporting

confidence: 56%

RUNX transcription factors: biological functions and implications in cancer

Chen,

Wang,

Yang

et al. 2024

Clin Exp Med

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Runt-related transcription factors (RUNX) are a family of transcription factors that are essential for normal and malignant hematopoietic processes. Their most widely recognized role in malignancy is to promote the occurrence and development of acute myeloid leukemia. However, it is worth noting that during the last decade, studies of RUNX proteins in solid tumors have made considerable progress, suggesting that these proteins are directly involved in different stages of tumor development, including tumor initiation, progression, and invasion. RUNX proteins also play a role in tumor angiogenesis, the maintenance of tumor cell stemness, and resistance to antitumor drugs. These findings have led to the consideration of RUNX as a tumor biomarker. All RUNX proteins are involved in the occurrence and development of solid tumors, but the role of each RUNX protein in different tumors and the major signaling pathways involved are complicated by tumor heterogeneity and the interacting tumor microenvironment. Understanding how the dysregulation of RUNX in tumors affects normal biological processes is important to elucidate the molecular mechanisms by which RUNX affects malignant tumors.

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Section: Runx Proteins In the Landscape Of Cancer Expressionsupporting

confidence: 56%

RUNX transcription factors: biological functions and implications in cancer

Chen,

Wang,

Yang

et al. 2024

Clin Exp Med

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“…On the other hand, there are also plenty of reports of TFs acting as tumor suppressors in CRC; among them is FOXO3, whose downregulation correlates with a better prognosis in CRC patients [76,77]. Another example is RUNX3-this TF is a target of the TGF-β pathway and is downregulated in CRC patient samples [78]. It has been reported that RUNX3 can induce apoptosis [79] and inhibit metastasis and angiogenesis [80].…”

Section: Discussionmentioning

confidence: 99%

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)

Herrera-Orozco,

García-Castillo,

López-Urrutia

et al. 2023

CIMB

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Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< −1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA–miRNA–mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

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“…EZH2 has been shown to regulate RUNX3 expression ( 13 ). Based on results reported in our previous work ( 14 – 16 ), we aimed to investigate whether RUNX3 and EZH2 can evaluate the clinical efficacy of neoadjuvant therapy and prognosis of LARC.…”

Section: Introductionmentioning

confidence: 99%

Combined Detection of RUNX3 and EZH2 in Evaluating Efficacy of Neoadjuvant Therapy and Prognostic Value of Middle and Low Locally Advanced Rectal Cancer

Wang

et al. 2022

Front. Oncol.

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ObjectiveThis article investigated whether Runt-Related Transcription Factor 3 (RUNX3) and enhancer of zeste homolog 2 (EZH2) can be used to evaluate the clinical efficacy of neoadjuvant therapy and prognosis of locally advanced rectal cancer (LARC). MethodsEighty LARC patients admitted to the Tianjin Medical University Cancer Institute/Hospital and First Affiliated Hospital of Hebei North University from Jan 2015 to Jan 2016 were enrolled. The patients were followed up for 60 months through hospital visits. All patients received neoadjuvant chemoradiotherapy (long range radiotherapy + oral capecitabine) + total mesorecta excision (TME) surgery. The clinical efficacy of the treatments was evaluated through endoscopic, radiography, and tumor regression grade (TRG). In addition, expression level of RUNX3 and EZH2 was quantified via immunohistochemistry. The association of RUNX3 and EZH2 with clinicopathological characteristics of advanced tumors and efficacy of neoadjuvant therapy was explored. Logistic regression analysis was performed to identify predictors of efficacy of neoadjuvant chemoradiotherapy. Survival curve was used to evaluate the impact of RUNX3 and EZH2 on the prognosis of LARC patients.ResultsA total of 80 patients diagnosed with LARC were enrolled in the study. Expression of RUNX3 was elevated in 25 (31.25%) patients, whereas expression of EZH2 was upregulated in 44 (55.00%) patients. Analysis of tumor regression identified 10 cases with TRG grade 0 (pathologic complete response, PCR), 24 cases with TRG grade 1, 35 cases with TRG grade 2, and 11 cases with TRG grade 3. Furthermore, 38 cases had significant down-staging, and 42 cases showed no significant down-staging as revealed by endoscopy and imaging. Patients with high expression of RUNX3 showed better tumor regression response and down-staging compared with those with low expression of RUNX3 (P < 0.001, P < 0.001). Moreover, patients with low EZH2 expression achieved TRG grade 0 and 1 response and down-staging effect compared with those with high expression of EZH2 (P < 0.001, P < 0.001). Logistic regression analysis showed that high expression of RUNX3, low expression of EZH2, and clinical N (cN) stage were good predictors of tumor regression response and down-staging. The 5-year disease free survival (DFS) and overall survival (OS) were 48.75 (39/80) and 58.75% (47/80), respectively. The 5-year DFS and OS of patients with high RUNX3 expression were significantly higher than low RUNX3 expression, whereas the 5-year DFS and OS of patients with high EZH2 expression were significantly lower than low EZH2 expression (P < 0.001). Univariate survival analysis showed that RUNX3 expression, EZH2 expression, cN, clinical T (cT), pathological T (pT) and pathological N (pN) were significantly correlated with the 5-year DFS and 5-year OS. Multivariate survival analysis showed that EZH2 expression and PN were good predictors of 5-year DFS and 5-year OS, whereas RUNX3 was a good predictor of 5-year DFS but not 5-year OS.ConclusionsExpression level of RUNX3 and EZH2 accurately predicts clinical efficacy of neoadjuvant chemoradiotherapy and the prognosis of LARC patients, suggesting that RUNX3 and EZH2 can be used as pivotal clinical predictors for LARC.

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Expression, clinical significance and correlation of RUNX3 and HER2 in colorectal cancer

Cited by 4 publications

References 18 publications

RUNX transcription factors: biological functions and implications in cancer

RUNX transcription factors: biological functions and implications in cancer

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet)

Combined Detection of RUNX3 and EZH2 in Evaluating Efficacy of Neoadjuvant Therapy and Prognostic Value of Middle and Low Locally Advanced Rectal Cancer

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