Application of next-generation sequencing in resistance genes of neoadjuvant chemotherapy for esophageal cancer

Liu, Jizhao; Xing, Wei; Tian, Qingnan; Yin, Li; Liu, Xianben; Sun, Haibo; Gao, Kun; Chen, Xiankai; Zheng, Yan

doi:10.21037/tcr-20-322

Cited by 3 publications

(5 citation statements)

References 31 publications

(31 reference statements)

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“…Histone H4R3me2a mediated by PRMT1 promotes proliferation of CSCs and activates Notch and Wnt/β-catenin signaling, leading to enhanced drug resistance ( Zhao et al, 2019a ). Moreover, somatic mutations on the Notch1 gene were commonly found in patients with partial responses or stable diseases after neoadjuvant chemotherapy ( Liu et al, 2020 ). Yes-associated protein (YAP), a Hippo pathway coactivator, confers stem-cell-like properties on EC cells by upregulating SOX9 ( Wang L. et al, 2019 ).…”

Section: Cellular Componentsmentioning

confidence: 99%

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

Luan

Zeng

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, etc. Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.

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Section: Cellular Componentsmentioning

confidence: 99%

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

Luan

Zeng

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…We previously found that Notch1 mutations might be associated with NAC resistance in patients with ESCC through NGS ( 6 ). The results of the present study demonstrated that the mutation site was located in the Notch1-DLL4 binding site, and the mutant domain was found to be highly conserved through bioinformatics analysis, highlighting the importance of this mutation site.…”

Section: Discussionmentioning

confidence: 99%

“…The Notch1 protein consists of a total of 2,555 amino acid residues. The transcript NM_017617.3 is 9309 bp in length, and the coding sequence (CDS) length is 7,668 bp [1][2][3][4][5][6][7]668]. The mutation site is located in exon no.…”

Section: Notch1 Genetic Informationmentioning

confidence: 99%

“…In a previous study, we performed NGS on patients with esophageal cancer after NAC and compared them with the sequencing results of samples before chemotherapy. Ultimately, we discovered that the NM_017617.3:c.1348G>A (p. Glu450 Lys) mutation of the NOTCH1 gene was likely to be related to NAC resistance in esophageal cancer ( 6 ). Currently, 4 Notch receptors (Notch1–4) and 5 ligands (DLL1, 3, 4 and JAG1, 2) have been identified in mammals ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

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The Notch1 gene may control cell chemoresistance in esophageal squamous cell cancer

Gao¹,

Xing²,

Liu³

et al. 2021

Transl Cancer Res TCR

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Background: In our previous study, missense mutations in the Notch1 gene were found in chemotherapyresistant esophageal squamous cell cancer (ESCC) patients. In this study, we explored changes in the interaction between Notch1 and DLL4 resulting from missense mutations.Methods: Bioinformatics analysis was performed to assess and compare the different biological structures and functions of wild type (WT) and mutation type (MT) sequences of Notch1. A genetic information search was performed, and the results were analyzed using in silico modeling. Homology modeling of the Notch1 protein was carried out using Swiss-Model software, and modeling of site-directed mutations was carried out using PyMOL software to observe the protein structure. The Notch1-DLL4 ligand-receptor complex protein model was constructed, Wincoot software was used to determine site-directed mutations, and a protein-ligand interaction profiler (PLIP) was used to calculate the noncovalent interactions in the complex. Results:The mutation site was located in the region where Notch1 binds to DLL4. A careful examination of the in silico structural model revealed that the mutation caused an alteration in the surface charge, and the water-bridge bonds of the interaction between Notch1-DLL4 increased in number from 5 to 7.Conclusions: Notch1 gene missense mutation leads to an increase in the number of water-bridge bonds, thus enhancing the Notch1-DLL4 interaction, which may lead to tighter Notch1-DLL4 binding, either making the pathway easier to activate or increasing the length of time it is active.

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“…Chemotherapy has evolved over the past 100 years to become a standard cancer therapy ( 1 ), and is now recommended as treatment for cancers of the cervix ( 2 ), breast ( 3 ), stomach ( 4 ), lung ( 5 ), bowel ( 6 ), and esophagus ( 7 ). Traditionally, cytotoxic drugs are used for chemotherapy, which target rapidly proliferating cells such as cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Changes of proportions of circulating lymphocyte subsets in cancer patients after chemotherapy

Wang¹,

Wang²,

Cao³

2021

Transl Cancer Res TCR

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Background It remains unknown how chemotherapy affects circulating lymphocyte subsets and whether the pattern of change is related to prognosis in cancer patients. Methods Cancer patients who received chemotherapy between 2018/03/01 and 2019/12/31 were enrolled from the Hefei Cancer Hospital, Chinese Academy of Sciences. Peripheral blood samples were collected before and 3 weeks after the start of chemotherapy, and the proportions of T cells (CD3+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), B cells (CD19+), and Natural killer (NK) cells (CD3−CD56+) were examined by flow cytometry. Multivariable logistic regression analysis was employed to explore risk factors associated with overall survival within 12 months after the start of chemotherapy. Results A total of 167 patients with cancer were included in the analysis, including 14 cases of cervical cancer, 18 cases of breast cancer, 33 cases of gastric cancer, 48 cases of lung cancer, 21 cases of colorectal cancer, and 33 cases of esophageal cancer. The proportion of T cells (72.58%±10.44% vs. 80.67%±11.63%, P<0.001) and cytotoxic T cells (25.38%±8.87% vs. 39.20%±12.26%, P<0.001) significantly increased, while the proportion of helper T cells (45.58%±10.19% vs. 41.98%±10.47%, P<0.001), B cells (15.10%±5.23% vs. 11.29%±5.60%, P<0.001), and NK cells (19.33%±7.54% vs. 18.28%±7.62%, P<0.001) significantly decreased at 3 weeks after chemotherapy when compared to baseline levels. The overall mortality rate was 14.97% (25/167) within 1 year after the start of chemotherapy. Patients who survived showed a significantly less increase in cytotoxic T cells (13.38%±8.28% vs. 17.28%±7.97%, P=0.030) and less decrease in B cells (−3.58%±2.81% vs. −5.29%±3.03%, P=0.006) when compared to non-survivors. Greater decreases in helper T cells (OR 0.81, 95% CI, 0.68–0.96) and B cells (OR 0.72, 95% CI, 0.59–0.87), and a greater increase in cytotoxic T cells (OR 1.09, 95% CI, 1.03–1.16) were risk factors for poor overall survival. Conclusions Circulating lymphocyte subsets of cancer patients presented characteristic changes after chemotherapy. Patients with a greater decrease in helper T cells and B cells, or greater increase in cytotoxic T cells, may have worse survival.

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Application of next-generation sequencing in resistance genes of neoadjuvant chemotherapy for esophageal cancer

Cited by 3 publications

References 31 publications

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

The Notch1 gene may control cell chemoresistance in esophageal squamous cell cancer

Changes of proportions of circulating lymphocyte subsets in cancer patients after chemotherapy

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