Diagnostic Values of miR-21, miR-124, and M-CSF in Patients With Early Cervical Cancer

Ruan, Fang; Wang, Yunfei; Chai, Yifeng

doi:10.1177/1533033820914983

Cited by 17 publications

(14 citation statements)

References 40 publications

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“…Macrophage Colony Stimulating Factor (M-CSF) assays included in our review reported sensitivity, specificity, PPV, NPV, and AUC ranges of 68-87.7%, 64.7-94%,77.4-92%, 75-82.7%, and 0.75-0.86, respectively, [5,[46][47][48][49], with performance characteristics relatively similar across all studies. Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of Monocytes to macrophages.…”

Section: Discussionmentioning

confidence: 89%

“…Like many other circulating miRNAs, studies have established that miR-9 could be useful for early detection of cervical cancer, predicting cancer prognosis, and in monitoring clinical outcome of cancer disease [55]. And that, by examining the associations between miR-9 levels in exfoliated cells, cervical tissues or serum; and the diverse biological processes such as metabolism and apoptosis, there is a consensus across studies showing that elevated levels is valuable for evaluating risk of cervical Intraepithelial neoplasia (CIN) in suspected individuals [2,7,53,55,57,58], especially in conjunction with other equally useful markers such as miR-21, miR-155, miR-192, miR-203 and miR-205 to improve specificity for optimal treatment benefit [2,11,48,53,[59][60][61]. Although our review is in agreement with this general consensus on diagnostic relevance of miR-9 in detection of CIN2+ [2,11], coupled with reduced turnaround time (TAT), and non-invasive blood sampling [53,55]; more robust clinical translation studies with larger consecutive cohorts of women participants would be appropriate for adequate validation alongside cost evaluation prior to implementation.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of Monocytes to macrophages. Experimental studies have shown that increased expression of M-CSF and its receptor leads to recruitment of tumor-associated macrophages (TAMs) in different types of cancers that also stimulate cancer cell proliferation and migration [5,47,48]. Consequently, M-CSF overexpression in plasma levels serves as useful predictor of carcinogenesis, and poor prognosis [46].…”

Section: Discussionmentioning

confidence: 99%

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Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Onyango

Ogonda

Guyah

et al. 2020

Infect Agents Cancer

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Background Cervical cancer screening is slowly transitioning from Pappanicolaou cytologic screening to primary Visual Inspection with Acetic Acid (VIA) or HPV testing as an effort to enhance early detection and treatment. However, an effective triage tests needed to decide who among the VIA or HPV positive women should receive further diagnostic evaluation to avoid unnecessary colposcopy referrals is still lacking. Evidence from experimental studies have shown potential usefulness of Squamous Cell Carcinoma Antigen (SCC Ag), Macrophage Colony Stimulating Factor (M-CSF), Vascular Endothelial Growth Factor (VEGF), MicroRNA, p16INKa / ki-67, HPV E6/E7/mRNA, and DNA methylation biomarkers in detecting premalignant cervical neoplasia. Given the variation in performance, and scanty review studies in this field, this systematic review described the diagnostic performance of some selected assays to detect high-grade cervical intraepithelial neoplasia (CIN2+) with histology as gold standard. Methods We systematically searched articles published in English between 2012 and 2020 using key words from PubMed/Medline and SCOPUS with two reviewers assessing study eligibility, and risk of bias. We performed a descriptive presentation of the performance of each of the selected assays for the detection of CIN2 + . Results Out of 298 citations retrieved, 58 articles were included. Participants with cervical histology yielded CIN2+ proportion range of 13.7–88.4%. The diagnostic performance of the assays to detect CIN2+ was; 1) SCC-Ag: range sensitivity of 78.6–81.2%, specificity 74–100%. 2) M-CSF: sensitivity of 68–87.7%, specificity 64.7–94% 3) VEGF: sensitivity of 56–83.5%, specificity 74.6–96%. 4) MicroRNA: sensitivity of 52.9–67.3%, specificity 76.4–94.4%. 5) p16INKa / ki-67: sensitivity of 50–100%, specificity 39–90.4%. 6) HPV E6/E7/mRNA: sensitivity of 65–100%, specificity 42.7–90.2%, and 7) DNA methylation: sensitivity of 59.7–92.9%, specificity 67–98%. Conclusion Overall, the reported test performance and the receiving operating characteristics curves implies that implementation of p16ink4a/ki-67 assay as a triage for HPV positive women to be used at one visit with subsequent cryotherapy treatment is feasible. For the rest of assays, more robust clinical translation studies with larger consecutive cohorts of women participants is recommended.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Onyango

Ogonda

Guyah

et al. 2020

Infect Agents Cancer

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“…Consistent with our results, various independent studies have indicated that the expression level of circulating miR-21 was significantly increased in patients with CC compared to the healthy controls. 13,14 In addition, increased serum miR-21 level was strongly associated with lymph node metastasis of CC. 15 Figure 1.…”

Section: Discussionmentioning

confidence: 99%

A Novel Circulating MiRNA-Based Signature for the Diagnosis and Prognosis Prediction of Early-Stage Cervical Cancer

Qiu

Liang

Liu

et al. 2020

Technol Cancer Res Treat

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Background: MicroRNAs (miRNAs) have been shown to play a key role in regulating the progression of cervical cancer (CC). This study aimed to develop a circulating miRNA-based molecular signature for the diagnosis and prognosis prediction of early-stage CC. Methods: This study included 112 patients diagnosed with early-stage CC, 45 patients confirmed with cervical intraepithelial neoplasia (CIN) and 90 healthy subjects. Compared to the normal controls, the expression level of miR-21 was increased, while the levels of miR-125b and miR-370 were decreased in CC in both GSE30656 and The Cancer Genome Atlas (TCGA) cohort. The expression levels and diagnostic value of these candidate miRNAs were then validated through qRT-PCR. Their diagnostic and prognostic values for early-stage CC were further explored. Results: Compared to the patients with CIN and healthy subjects, serum miR-21 was increased, while serum miR-125b and serum miR-370 were reduced in early-stage CC. In addition, combining these molecules yielded good performance for differentiating early-stage CC from CIN or healthy subjects. Moreover, strong association was found between serum miR-21 and lymph node metastasis (LNM) as well as recurrence-free survival of early-stage CC. Similar observations were found for serum miR-125b and serum miR-370. Patients with simultaneously high serum miR-21 + low serum miR-125b + low serum miR-370 suffered a high risk of LNM and recurrence, while those with low serum miR-21 + high serum miR-125b + high serum miR-370 had little risk for LNM and recurrence. Conclusions: Combining serum miR-21, miR-125b and miR-370 as a miRNA-based signature is promising for the detection and prognosis prediction of early-stage CC.

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“…Another xenograft mouse model also demonstrated that miR-21 is able to promote tumor growth [ 63 ]. In recent study, the diagnostic values of miR-21 were verified, mainly by the positive correlation of miR-21 and M-CSF expression in cervical cancer ( r = 0.6825, p < 0.001) [ 64 ]. Another report also manifested that the expression of miR-21 was induced by CSF-1R signaling via PI3K pathway activation [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

Chen

Lai

Hsuuw³

et al. 2021

IJMS

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Macrophage colony-stimulating factor (M-CSF or CSF-1) is known to have a broad range of actions on myeloid cells maturation, including the regulation of macrophage differentiation, proliferation and survival. Macrophages generated by M-CSF stimulus have been proposed to be alternatively activated or M2 phenotype. M-CSF is commonly overexpressed by tumors and is also known to enhance tumor growth and aggressiveness via stimulating pro-tumor activities of tumor-associated macrophages (TAMs). Currently, inhibition of CSF-1/CSF-1R interaction by therapeutic antibody to deplete TAMs and their pro-tumor functions is becoming a prevalent strategy in cancer therapy. However, its antitumor activity shows a limited single-agent effect. Therefore, macrophages in response to M-CSF interruption are pending for further investigation. To achieve this study, bone marrow derived macrophages were generated in vitro by M-CSF stimulation for 7 days and then continuously grown until day 21 in M-CSF absence. A selective pressure for cell survival was initiated after withdrawal of M-CSF. The surviving cells were more prone to M2-like phenotype, even after receiving interleukin-4 (IL-4) stimulation. The transcriptome analysis unveiled that endogenous CSF-1 level was dramatically up-regulated and numerous genes downstream to CSF-1 covering tumor necrosis factor (TNF), ras-related protein 1 (Rap1) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway were significantly modulated, especially for proliferation, migration and adhesion. Moreover, the phenomenal increase of miR-21-5p and genes related to pro-tumor activity were observed in parallel. In summary, withholding of CSF-1/CSF-1R interaction would rather augment than suspend the M-CSF-driven pro-tumor activities of M2 macrophages in a long run.

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Diagnostic Values of miR-21, miR-124, and M-CSF in Patients With Early Cervical Cancer

Cited by 17 publications

References 40 publications

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

A Novel Circulating MiRNA-Based Signature for the Diagnosis and Prognosis Prediction of Early-Stage Cervical Cancer

Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

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