Detection of sputum cofilin-1 as indicator of malignancy

Rangel, Maristela Peres; Antonângelo, Leila; Acencio, Milena Marques Pagliarelli; Faria, Caroline Silvério; Sá, V.K. de; Leao, Patrícia; Farhat, Cecília; Fabro, Alexandre Todorovic; Filho, A. Longatto; Reis, Rui Manuel; Takagaki, Teresa Yae; Capelozzi, Vera Luíza

doi:10.1590/1414-431x20187138

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…Further analysis is needed to assess their role in lymph node metastasis risk. However, CFL-1 levels association with dedifferentiation, infiltration depth, pathological staging, and presence of lymph node metastasis have also been found in other cancer types [ 11 – 13 , 37 , 38 ]. It is possible to speculate that the invasive margin may be region within the tumor that exhibits the highest levels of CFL-1, which increases aggressiveness and leads to local dissemination.…”

Section: Discussionmentioning

confidence: 99%

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes

et al. 2021

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Background Colorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification. Methods CFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan–Meier survival analysis was used to evaluated overall survival. Results Bioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes. Conclusions We demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.

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Section: Discussionmentioning

confidence: 99%

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes

et al. 2021

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“…Other bodily fluids: The analysis of stool-derived DNA has been recently validated as a powerful diagnostic tool for colorectal cancer [107], while sputum DNA and protein content has promising potential in the context of lung cancer [108]. Pleural effusions, finally, are source of DNA biomarkers for lung cancer [109] and malignant pleural mesothelioma [110], and the presence of Epithelial Cell Adhesion Molecule (EpCAM) + microparticles allows distinction between malignant and non-malignant pleural effusions [111].…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis

Rubis

Krishnan

Bebawy

2019

Trends in Pharmacological Sciences

405

343

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Liquid biopsy, consisting in the non-invasive analysis of circulating tumor-derived material (the Tumor Circulome), represents an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies. Within the tumor circulome, ctDNA and CTCs are the only components whose clinical application is FDA-cleared. Extracellular vesicles, ctRNA and tumor-educated platelets are relatively novel tumor circulome constituents with promising potential at each stage of cancer management. Here, we discuss the clinical applications of each element of the tumor circulome and the prevailing factors that currently limit implementation in clinical practice. We also detail the most recent technological developments in the field, which demonstrate potential in improving the clinical value of liquid biopsies. Commented [GDR3R2]: Thanks for doing that Commented [MK(2]: Please include all weblinks in a separate section before "References", entitled "Resources" Commented [MK(1]: Please include all weblinks in a separate section before "References", entitled "Resources" Commented [MK(4]: Since this is how it is depicted in the Figure. Commented [MK(5]: I suggest that this be converted into "Key Figure". The Figure represents the contents of the review well. Commented [MK(6]: Are the authors talking about advances in sample isolation? I'd encourage you to give examples to align the readers to what advancements the authors are referring to. Commented [GDR7R6]: Done with some of the innovations discussed in the following chapters.

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“…In the present tissue spot, the stage IV samples expressed low cofilin-1 and high Twist-1 levels (data not shown). In contrast to these findings, a recent report indicated that sputum cofilin-1 levels were higher in T4 and N stage of lung cancer patients (27). Serum cofilin-1 levels were further reported to be increased in the advanced stage of patients with lung cancer (28).…”

Section: Discussionmentioning

confidence: 91%

Comparison of cofilin‑1 and Twist‑1 protein expression in human non‑small cell lung cancer tissues

Chang¹,

Chang

Leu

et al. 2019

Oncol Rep

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Metastasis is the primary cause of mortality in patients with non-small cell lung cancer (NSCLC). Actin cytoskeletal reorganization is usually accompanied by the epithelial-mesenchymal transition (EMT)-induced invasion and metastasis of cancer cells. In the present study, expression levels of the actin-associated protein cofilin-1 and of the pivotal EMT molecule Twist-1 were determined in NSCLC tissues. Using lung cancer tissue arrays, the identification of 67.4% of tissue spots that exhibited reciprocal levels of cofilin-1 and Twist-1 was achieved by immunohistochemical (IHC) staining. This reciprocal expression pattern was also detected in 21 out of 25 clinicopathological NSCLC tissue sections, and in 10 out of 15 NSCLC cell lines. In addition, high levels of cofilin-1 and low levels of Twist-1 accounted for 80 and 71.5% of the reciprocal expression pattern in tissue arrays and clinicopathological tissue samples, respectively. This pattern was also detected in normal lung tissues, stage I and II lung cancer tissues, and adenocarcinoma subtypes of NSCLC tissues. Although cofilin-1 and Twist-1 were expressed inversely, a positive correlation of these two proteins was present in normal lung tissues and lung tumor tissues. Furthermore, enforced expression of cofilin-1 suppressed the expression level of Twist-1 in NSCLC H1299 cells. An on-line Kaplan-Meier survival analytic tool allowed access to a public microarray dataset with a maximum of 1,926 NSCLC samples. The analysis revealed that high expression levels of both cofilin-1 (CFL1) and Twist-1 (TWIST1) genes were associated with decreased survival of NSCLC patients, notably with regard to the adenocarcinoma subtype. The analysis was conducted using the multivariate Cox regression model. Although the reciprocal association of the expression levels of cofilin-1 and Twist-1 with the survival rate of NSCLC patients requires additional information, it may be a significant indicator of the progression of NSCLC.

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Detection of sputum cofilin-1 as indicator of malignancy

Cited by 6 publications

References 19 publications

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes

Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis

Comparison of cofilin‑1 and Twist‑1 protein expression in human non‑small cell lung cancer tissues

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