Identification of biomarkers in colon cancer based on bioinformatic analysis

Zhu, Ying; Sun, Leitao; Yu, Jinping; Xiang, Yuying; Shen, Minhe; Wasan, Harpreet; Ruan, Shanming; Qiu, Shengliang

doi:10.21037/tcr-20-845

Cited by 8 publications

(11 citation statements)

References 49 publications

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“…However, the converse was not true, as only 13.3% (PPV =13.3%) of samples with high TMB were classified as MSIhigh/dMMR. In addition, patients with low-TMB were associated with MSS/pMMR (96.2%), and these results are consistent with earlier studies (8,32,37).…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, we performed a survival analysis of the panel-TMB measured by the GP645 using TCGA database and found that high-TMB patients were strongly associated with poor OS in CRC. Previous studies confirmed that TMB measured by a cancer-related gene panel (CRGP) could be used for prognosis and to predict the benefits of immunotherapy (30)(31)(32). Thus, these findings indicated that higher panel-TMB might be an adverse prognostic factor for CRC.…”

Section: Discussionmentioning

confidence: 69%

“…To established a prognostic system for cancer patients, cancer-related genes have been used to develop cancer panels in lung cancer (28), malignant lymphoma (29), melanoma (30), gastric cancer (31), and other cancers (32).…”

Section: Discussionmentioning

confidence: 99%

“…We determined the median value as the threshold for panel- KMT2C [38] FCGR2A [37] MYC [35] NCOR1 [33] CHD4 [32] HLA-B [32] KMT2D [32] SPEN [32] NOTCH2 [27] BCR [26] KMT2B [26] MAP3K1 [25] HLA-A [23] LRP1B [23] NOTCH1 [23] TP53 [23] FAT1 [22] KAT6A [21] PED4DIP [21] PRSS1 [21] ARID1A [20] ARID1B [20] CIC [20] HLA-DRB51 [20] FAT3 [ A-DRB5 [20] ClC [20] ARID1B [20] ARID1A [20] PRSS1 [21] PED4DIP [21] KAT6A [21] FAT1 [22] TP53 [23] NOTCH1 [23] LRP1B [23] HLA-A [23] MAP3K1 [25] KMT2B [26] BCR [26] NOTCH2 [27] SPEN [32] KMT2D [32] HLA-B [32] CHD4 [32] NCOR1 [33] MYC [35] FCGR2A [37] KMT2C [38]<...>…”

Section: Higher Tmb Estimated By the Panel-tmb Is Associated With Improved Osmentioning

confidence: 99%

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Tumor mutation burden determined by a 645-cancer gene panel and compared with microsatellite instability and mismatch repair genes in colorectal cancer

Zhou¹,

Li²,

Wei³

et al. 2021

J Gastrointest Oncol

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Background: Tumor mutation burden (TMB) assessed by tumor-related gene panels (CRGP), microsatellite instability (MSI), and mismatch repair (MMR) has been proven to be associated with prognosis, and these factors are prognostic indicators in predicting the benefits of immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CRGPs, MSI, and MMR is associated with overall survival (OS) in patients with colorectal cancer (CRC) remains to be explored. Methods:The prognostic threshold of the panel-TMB was explored by a panel of 645 genes (GP645) from 41 CRC patients in Jiangsu Cancer Hospital (JCH dataset). The results were further validated using 531 CRC patients from The Cancer Genome Atlas (TCGA) database.Results: Mutations of the GP645 genes were distributed on 21 chromosomes. Spearman correlation analysis showed that the panel-TMB was positively correlated with TMB measured by whole-exome sequencing (WES) (wTMB) in the TCGA dataset (R=0.75, P<0.001). Kaplan-Meier survival analysis demonstrated that higher panel-TMB in CRC patients was significantly associated with a poor OS (P=0.0062).MSI and MMR status were determined using the GP645 by next-generation sequencing (NGS). The proportions of MSI-H and dMMR accounted for less than 10% in CRC, the vast majority of MSI-H/dMMR samples also had high TMB [positive predictive value (PPV) =66.6%], and only 13.3% of samples with high TMB were classified as MSI-high/dMMR. In addition, patients with low-TMB were associated with MSS/ pMMR (96.2%), and these results are consistent with earlier studies.Conclusions: GP645 was constructed to evaluate OS in Chinese CRC patients. Panel-TMB and MSI/ MMR might be potential prognostic predictors of CRC patients using the GP645.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Higher Tmb Estimated By the Panel-tmb Is Associated With Improved Osmentioning

confidence: 99%

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Tumor mutation burden determined by a 645-cancer gene panel and compared with microsatellite instability and mismatch repair genes in colorectal cancer

Zhou¹,

Li²,

Wei³

et al. 2021

J Gastrointest Oncol

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“…DEPDC1, DEP (disheveled, EGL-10, pleckstrin) domain-containing 1 protein, is a novel oncoantigen upregulated in multiple types of cancers, including HCC ( Kanehira et al, 2007 ; Qu et al, 2018 ; Zhao et al, 2019 ; Zhu et al, 2020 ). DEPDC1 is thought to be a novel diagnostic marker for human cancers and a molecular-target for novel therapeutic drugs or cancer peptide-vaccine.…”

Section: Introductionmentioning

confidence: 99%

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway

Tian

Zhong

et al. 2021

Front. Cell Dev. Biol.

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The tumor metastasis is the major hurdle for the treatment of advanced hepatocellular carcinoma (HCC), due in part to the lack of effective systemic treatments. DEPDC1, a novel oncoantigen upregulated in HCC, is thought to be a molecular-target for novel therapeutic drugs. Artemisia argyi is a traditional Chinese medicine with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Artemisia argyi essential oil (AAEO) in suppressing metastasis of HCC by targeting DEPDC1. Assessment of AAEO cytotoxicity was performed by MTT assay. Anti-metastatic effects of AAEO were investigated in vitro using wound healing and transwell assays. The HepG2 cells were transduced with lentiviral vector containing luciferase (Luc). A metastasis model of nude mice was established by tail vein injection of HepG2-Luc cells. The nude mice were treated with AAEO (57.5, 115, and 230 mg/kg) or sorafenib (40 mg/kg). Metastasis of HCC cells was monitored via in vivo bioluminescence imaging. After treatment for 21 days, tissues were collected for histological examination and immunohistochemistry analysis. Gene and protein levels were determined by real-time quantitative PCR and western blotting. The results revealed that AAEO significantly inhibits the migration and invasion in vitro in a concentration-dependent manner. In vivo assays further confirmed that AAEO markedly inhibits HCC metastasis into lung, brain, and femur tissues and exhibits low toxicity. Our results suggested that AAEO significantly downregulates the mRNA and protein expression of DEPDC1. Also, AAEO attenuated Wnt/β-catenin signaling through reduction of Wnt1 and β-catenin production. Moreover, AAEO prevented epithelial-mesenchymal transition (EMT) by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that DEPDC1 promoted HCC migration and invasion via Wnt/β-catenin signaling pathway and EMT. These results demonstrate that AAEO effectively inhibits HCC metastasis via attenuating Wnt/β-catenin signaling and inhibiting EMT by suppressing DEPDC1 expression. Thus, AAEO likely acts as a novel inhibitor of the DEPDC1 dependent Wnt/β-catenin signaling pathway.

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