Cystatin SN promotes epithelial-mesenchymal transition and serves as a prognostic biomarker in lung adenocarcinoma

Yang, Jian; Luo, Gaomeng; Li, Chang; Zhao, Zhunlin; Ju, Sheng; Li, Qifan; Chen, Zhike; Ding, Cheng; Tong, Xin; Zhao, Jun

doi:10.1186/s12885-022-09685-z

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…In gastric cancer, CST1 can promotes gastric cancer progression by inhibiting ferroptosis via regulating GPX4 protein stability or by activating the Wnt pathway [36,37]. In lung cancer, CST1 can promote epithelial-mesenchymal transition and serves as a prognostic biomarker [38]. However, our present study did not investigate the underlying mechanism of CST1-involved poor prognosis of GI-DLBCL, partially because there is no proper cell or animal model of GI-DLBCL.…”

Section: Discussionmentioning

confidence: 79%

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-cell Lymphoma

Wang,

Yang,

Chen

et al. 2024

Med Sci Monit

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Background:Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extranodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. Material/Methods:We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. Results:CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. Conclusions:CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

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Section: Discussionmentioning

confidence: 79%

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-cell Lymphoma

Wang,

Yang,

Chen

et al. 2024

Med Sci Monit

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“…The gene markers for NMF4 were often associated with ECM-related functions. For example, a high expression of CST1 is known as an unfavorable prognostic marker across tumors and experimentally induced EMT in lung cancers [ 21 ]. COMP encodes noncollagenous ECM profiles and might promote EMT in cancer cells [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…Factors such as the immunogenicity of the tumor, the overall immune competence of the patient and specific characteristics of the tumor microenvironment can influence the efficacy of BCG therapy. Among the genetic factors, specific HLA (human leukocyte antigen) types have been reported to be associated with the variable response to BCG treatment [ 21 ]. A high level of HLA-DRA and HLA-DRB , which are MHC class II molecules, emerged as potential markers for NMF1, indicating BCG responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Transcription Profiling of Bladder Cancers Dictate the Response to BCG Treatment and Disease Progression

Lee,

Kim

et al. 2023

IJMS

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Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.

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“…In tumor development and cancer progression the balance between cystatins and cysteine peptidases may be disrupted 47 . Cathepsin F (CTSF) was observed to have an anti-tumor effect in lung adenocarcinoma (LUAD) 48 whereas Cystatin-SN (CST1) promotes the epithelial-mesenchymal transition in LUAD cells 49 . The CST1-CTSF model (Figure S6) suggests that the mechanism of action of CST1, which is highly expressed in LUAD 49 , may be to inhibit the anti-tumorigenic activity of CTSF.…”

Section: Role Of Cystatins In Tumorigenesismentioning

confidence: 99%

ZEPPI: Proteome-scale sequence-based evaluation of protein–protein interaction models

Zhao,

Petrey,

Murray

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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We introduce ZEPPI (Z-score Evaluation of Protein–Protein Interfaces), a framework to evaluate structural models of a complex based on sequence coevolution and conservation involving residues in protein–protein interfaces. The ZEPPI score is calculated by comparing metrics for an interface to those obtained from randomly chosen residues. Since contacting residues are defined by the structural model, this obviates the need to account for indirect interactions. Further, although ZEPPI relies on species-paired multiple sequence alignments, its focus on interfacial residues allows it to leverage quite shallow alignments. ZEPPI can be implemented on a proteome-wide scale and is applied here to millions of structural models of dimeric complexes in the E scherichia coli and human interactomes found in the PrePPI database. PrePPI’s scoring function is based primarily on the evaluation of protein–protein interfaces, and ZEPPI adds a new feature to this analysis through the incorporation of evolutionary information. ZEPPI performance is evaluated through applications to experimentally determined complexes and to decoys from the CASP-CAPRI experiment. As we discuss, the standard CAPRI scores used to evaluate docking models are based on model quality and not on the ability to give yes/no answers as to whether two proteins interact. ZEPPI is able to detect weak signals from PPI models that the CAPRI scores define as incorrect and, similarly, to identify potential PPIs defined as low confidence by the current PrePPI scoring function. A number of examples that illustrate how the combination of PrePPI and ZEPPI can yield functional hypotheses are provided.

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Cystatin SN promotes epithelial-mesenchymal transition and serves as a prognostic biomarker in lung adenocarcinoma

Cited by 8 publications

References 52 publications

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-cell Lymphoma

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-cell Lymphoma

Longitudinal Transcription Profiling of Bladder Cancers Dictate the Response to BCG Treatment and Disease Progression

ZEPPI: Proteome-scale sequence-based evaluation of protein–protein interaction models

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