Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer

Wang, Shujie; Liu, Wenjing; Ni, Yueli; Wang, Lifeng; Zhu, Yuzhi; Shi, Qiong; Yi, Zihan; Wang, Wenjie; Liu, Huan; Yang, Lijuan; Kuang, Yingmin; Zhu, Yuechun; Zhang, Qiao; Yang, Zhe

doi:10.7150/jca.54576

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…These data suggest that NCOA1 and DNMT3A levels might be used as biomarkers of EC malignancy. In contrast, dysregulation of ERCC3 (Excision repair cross-complementation group 3) levels has not been previously associated to EC, although different studies highlight the suppressor role of ERCC3 silencing in different cancers, as pancreatic or liver carcinomas [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression

et al. 2023

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Background Endometrial cancer (EC) is the most common cancer of the female reproductive organs. Despite the good overall prognosis of most low-grade ECs, FIGO I and FIGO II patients might experience tumor recurrence and worse prognosis. The study of alterations related to EC pathogenesis might help to get insights into underlying mechanisms involved in EC development and progression. Methods Core tumoral samples were used to investigate the role of C1GALT1 in EC by immunohistochemistry (IHC). ECC-1 cells were used as endometrioid EC model to investigate the effect of C1GALT1 depletion using C1GALT1 specific shRNAs. SILAC quantitative proteomics analyses and cell-based assays, PCR, qPCR, WB, dot-blot and IHC analyses were used to identify, quantify and validate dysregulation of proteins. Results Low C1GALT1 protein expression levels associate to a more aggressive phenotype of EC. Out of 5208 proteins identified and quantified by LC-MS/MS, 100 proteins showed dysregulation (log2fold-change ≥ 0.58 or ≤-0.58) in the cell protein extracts and 144 in the secretome of C1GALT1 depleted ECC-1 cells. Nine dysregulated proteins were validated. Bioinformatics analyses pointed out to an increase in pathways associated with an aggressive phenotype. This finding was corroborated by loss-of-function cell-based assays demonstrating higher proliferation, invasion, migration, colony formation and angiogenesis capacity in C1GALT1 depleted cells. These effects were associated to the overexpression of ANXA1, as demonstrated by ANXA1 transient silencing cell-based assays, and thus, correlating C1GALT and ANXA1 protein expression and biological effects. Finally, the negative protein expression correlation found by proteomics between C1GALT1 and LGALS3 was confirmed by IHC. Conclusion C1GALT1 stably depleted ECC-1 cells mimic an EC aggressive phenotype observed in patients and might be useful for the identification and validation of EC markers of progression.

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Section: Discussionmentioning

confidence: 99%

In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression

et al. 2023

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“…28 ERCC3 is an important member of nucleotide excision repair overexpressed in a variety of cancers. 29,30 Mutations in genes involved in DNA repair have been linked to crizotinib resistance. GNAS is a cancer proto-oncogene that exists in pituitary adenoma, appendiceal mucinous tumor and colon adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…DNMT3A encodes a DNA methyltransferase, which is thought to play an important role in tumorigenesis and is associated with cancer progression 28 . ERCC3 is an important member of nucleotide excision repair overexpressed in a variety of cancers 29,30 . Mutations in genes involved in DNA repair have been linked to crizotinib resistance.…”

Section: Discussionmentioning

confidence: 99%

Dynamic monitoring of circulating tumor DNA to analyze genetic characteristics and resistance profile of lorlatinib in ALK positive previously treated NSCLC

Zhang

et al. 2023

Thoracic Cancer

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Background To dynamically monitor the changes of genomic characteristics during lorlatinib treatment and analyze the resistance profile of lorlatinib in ALK‐positive advanced Chinese patients with non‐small cell lung cancer (NSCLC) with first‐ and second‐generation ALK inhibitor resistance. Methods Ten eligible patients who were from a phase 2 study in China and admitted to the Fifth Medical Center of PLA General Hospital were analyzed. Blood samples were collected for next‐generation sequencing (NGS) to characterize genetic variation at baseline, during treatment, and after disease progression. Results Among the 10 patients treated with lorlatinib, objective response rate (ORR) was 50%. The median progression‐free survival (PFS) was 13.3 months, and median overall survival (OS) was 15.6 months. At baseline, the mutation frequency of ALK in circulating tumor DNA (ctDNA) was higher in the group who received two lines of previous anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs), and a similar trend was observed for TP53. After one follow‐up cycle, the decreased variant allele frequency (VAF) had a trend to be predictive for responses. In six patients in which blood samples had been taken after lorlatinib resistance, ALK compound mutations were found in three patients (50%), which were G1202R/L1196M, L1196M/D1203N, and G1202R/F1174C. The DNMT3A N403Tfs*4, ERCC3 E259D, and GNAS p.A436_P459del variants were only detected after progression in two of the other three patients without ALK compound mutations. Conclusions The dynamic changes of genomic characteristics during lorlatinib treatment revealed the mutation landscape of Chinese patients with NSCLC after ALK‐TKI resistance, indicated that the resistance profile of lorlatinib were heterogeneous, which laid the foundation for subsequent treatment to overcome lorlatinib resistance.

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“…Tissue microarrays (MME1004i) were purchased from xi,an Taibosi Biological Technology Co., Ltd. (Xian, China). Immunohistological assessment was performed as previously described ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma

Xiong

et al. 2022

Front. Immunol.

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Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is the first enzyme in the de novo purine nucleotide synthesis pathway and is essential for cell development. However, the effect of PRPS1 on melanoma proliferation and metastasis remains unclear. This study aimed to investigate the regulatory mechanism of PRPS1 in the malignant progression of melanoma. Here, we found PRPS1 was upregulated in melanoma and melanoma cells. In addition, our data indicated that PRPS1 could promote the proliferation and migration and invasion of melanoma both in vitro and in vivo. PRPS1 also could inhibit melanoma cell apoptosis. Furthermore, we found NRF2 is an upstream transcription factor of PRPS1 that drive malignant progression of melanoma.

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Overexpression of ERCC3 is associated with poor prognosis in patients with pancreatic cancer

Cited by 5 publications

References 24 publications

In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression

In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression

Dynamic monitoring of circulating tumor DNA to analyze genetic characteristics and resistance profile of lorlatinib in ALK positive previously treated NSCLC

NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma

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