Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

Chen, Chun‐Chi; Chiou, Shiow-Her; Yang, Chenglin; Chow, Kuan‐Chih; Lin, Tze–Yi; Chang, Hui‐Wen; You, Weir-Chiang; Huang, Hisu-Wen; Chen, Chien‐Min; Chen, Nien-Cheng; Chou, Fen‐Pi; Chou, Ming-Chih

doi:10.18632/oncotarget.20414

Cited by 30 publications

(31 citation statements)

References 36 publications

(82 reference statements)

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“…We have previously demonstrated that the over-expression of gelsolin protects ovarian cancer cells against cisplatin-induced death and could be a potential target for treatment 26 . pGSN has also been implicated in pathological disease conditions such as prostate cancer, breast cancer, sepsis, arthritis, microbial infections, hemodialysis and other inflammatory disorders 22,27–31 . Although pGSN is highly secreted in OVCA cells, its role in patients’ plasma has not been investigated yet.…”

Section: Introductionmentioning

confidence: 99%

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer

Asare-Werehene

Communal

Carmona

et al. 2019

Sci Rep

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Ovarian cancer (OVCA) patients with suboptimal residual disease (RD) and advanced stages have poor survival. pGSN is an actin binding protein which protects OVCA cells from cisplatin-induced death. There is an urgent need to discover reliable biomarkers to optimize individualized treatment recommendations. 99 plasma samples with pre-determined CA125 were collected from OVCA patients and pGSN assayed using sandwich-based ELISA. Associations between CA125, pGSN and clinicopathological parameters were examined using Fisher’s exact test, T test and Kruskal Wallis Test. Univariate and multivariate Cox proportional hazard models were used to statistically analyze clinical outcomes. At 64 µg/ml, pGSN had sensitivity and specificity of 60% and 60% respectively, for the prediction of RD where as that of CA125 at 576.5 U/mL was 43.5% and 56.5% respectively. Patients with stage 1 tumor had increased levels of pre-operative pGSN compared to those with tumor stage >1 and healthy subjects (P = 0.005). At the value of 81 µg/mL, pGSN had a sensitivity and specificity of 75% and 78.4%, respectively for the detection of early stage OVCA. At the value of 0.133, the Indicator of Stage 1 OVCA (ISO1) provided a sensitivity of 100% at a specificity of 67% (AUC, 0.89; P < 0.001). In the multivariate Cox regression analysis, pGSN (HR, 2.00; CI, 0.99–4.05; P = 0.05) was an independent significant predictor of progression free survival (PFS) but not CA125 (HR, 0.68; CI, 0.41–1.13; P = 0.13). Pre-operative circulating pGSN is a favorable and independent biomarker for early disease detection, RD prediction and patients’ prognosis.

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Section: Introductionmentioning

confidence: 99%

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer

Asare-Werehene

Communal

Carmona

et al. 2019

Sci Rep

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“…Clinical studies have reported a strong association between circulating pGSN levels and inflammation-associated clinical states, but their potential regulatory roles in relation to immune cells were only revealed recently. pGSN was reported to inactivate CD4+ T cells through CD37 signaling and to induce the apoptosis of activated CD8+ T cells through membrane-bound FasL [24]. Similarly, the observed lower circulating pGSN level in patients with HNC compared with in healthy controls could reflect their consumption by CD8+ T cells that triggered apoptosis.…”

Section: Discussionmentioning

confidence: 97%

“…pGSN expression is implicated in various pathological conditions, such as acute respiratory distress syndrome, sepsis, acute hepatic failure, myonecrosis [19][20][21], and various cancers [22,23]. Recently, the role of pGSN in apoptosis induction in tumor-infiltrating CD8+ T lymphocytes has been demonstrated through FasL binding in prostate cancer [24]. However, the significance of circulating pGSN levels in HNC prognosis and the relevant clinicopathological implications warrant elucidation.…”

Section: Introductionmentioning

confidence: 99%

Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand

Chiu

Wang

Asare-Werehene

et al. 2020

Cancers

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Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL.

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“…GSN or Gelsolin gene encodes a protein that is involved in assembly and disassembly of actin filaments. Gelsolin has been attributed in prostate tumorigenesis and malignant transformation 56 , 57 . The C–C type chemokine 14 gene is known to induce targeted cell migration and is thought to play a role in carcinogenesis and metastasis of certain malignancies including breast cancer 58 , 59 .…”

Section: Discussionmentioning

confidence: 99%

Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery

Vizeacoumar

Guo

Dwernychuk

et al. 2021

Sci Rep

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Gastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.

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Secreted gelsolin desensitizes and induces apoptosis of infiltrated lymphocytes in prostate cancer

Cited by 30 publications

References 36 publications

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer

Pre-operative Circulating Plasma Gelsolin Predicts Residual Disease and Detects Early Stage Ovarian Cancer

Circulating Plasma Gelsolin: A Predictor of Favorable Clinical Outcomes in Head and Neck Cancer and Sensitive Biomarker for Early Disease Diagnosis Combined with Soluble Fas Ligand

Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery

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