(searched for: doi:10.4103/jcrt.jcrt_410_17)
Published: 1 December 2022
Open Access Rheumatology: Research and Reviews, pp 291-299; https://doi.org/10.2147/oarrr.s391494
Background: Rheumatoid arthritis (RA) is a common systemic inflammatory disease. Collagen triple helix repeat containing-1 (CTHRC1) is a unique gene product able to reduce collagen deposition. The present study aimed to assess CTHRC1 level in RA patients and to uncover its relation to clinical, laboratory and radiological findings. Methods: The study included 60 adult RA patients. In addition, there were 60 control subjects who included patients with osteoarthritis (n = 20) and reactive arthritis (n = 20) and healthy controls (n = 20). Serum CTHRC1 levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Disease activity was calculated using the Disease Activity Score (DAS28-CRP). Radiological damage was evaluated using the Simple Erosion Narrowing Score (SENS). Results: There was significantly higher serum CTHRC1 levels in RA patients when compared to OA, ReA and control groups [median (IQR): 4.66 (1.68– 11.7) versus 1.88 (1.14– 2.94), 1.55 (0.98– 3.15) and 1.14 (0.85– 1.3) mg/dL, respectively, p < 0.001]. There was significantly higher CTHRC1 levels in patients with higher disease activity [median (IQR): 2.23 (1.4– 4.73) versus 6.55 (4.66– 12.0) mg/dL, p = 0.004]. Patients with higher SENS had significantly higher CTHRC1 [median (IQR): 1.99 (1.4– 4.66) versus 9.75 (4.39– 12.63) mg/dL, p < 0.001] and DAS28 [median (IQR): 4.25 (2.9– 5.2) versus 5.4 (4.65– 5.8), p = 0.01]. Conclusion: Serum CTHRC1 levels are related to disease severity and radiological affection in RA patients.
Published: 20 April 2021
Journal of Southern Medical University, Volume 41, pp 549-554
To explore the role of CTHRC1 in regulating the proliferation and apoptosis of papillary thyroid cancer cells. Papillary thyroid cancer TPC-1 cells were transfected with a small interfering RNA (siRNA) targeting CTHRC1, with the cells transfected with a scrambled sequence as the negative control. The changes in cell proliferation and apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry with AV/PI double staining, respectively. The expression of c-caspase-3, c-PARP1 and phosphorylation of ERK1/2 in the cells were examined with Western blotting. Transfection with the siRNA sequence significantly decreased the mRNA and protein levels of CTHRC1 in TCP-1 cells (P < 0.05). Compared with blank and negative control cells, TCP-1 cells with RNA interference of CTHRC1 showed significantly lowered proliferative activity and enhanced cell apoptosis (P < 0.05) with significantly increased expressions of c-caspase-3 and c-PARP1 and phosphorylation of ERK1/2 (P < 0.05). RNA interference of CTHRC1 promotes the proliferation and inhibits apoptosis of papillary thyroid cancer cells possibly by activating the ERK1/2 pathway.
International Journal of Molecular Sciences, Volume 22; https://doi.org/10.3390/ijms22052426
Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.
Journal of Oncology, Volume 2021, pp 1-20; https://doi.org/10.1155/2021/8895330
Urine can accumulate systemic changes with no mechanism to be stable, which may reflect early changes associated with physiological or pathophysiological processes. To explore the potential value of the urine proteome, two rat models were established by intrahepatic injection of two different hepatoma cell lines, CBRH-7919 and RH-35. Urine samples were collected and analyzed. Compared with controls, the two models exhibited different numbers and types of differentially expressed urinary proteins despite having similar histological results. The results were compared with the urine proteome of a Walker 256 (W-256) liver tumor model. The differentially expressed urinary protein patterns in the three models were different. These findings demonstrate that changes in the urine proteomes of the two models can be detected at early stages and that the patterns of differentially expressed urinary proteins can differ even when the histological results are similar. Urinary proteins have potential utility for distinguishing among different tumor cells grown in the same organ.
Oncotargets and Therapy, pp 11193-11209; https://doi.org/10.2147/ott.s274092
Let-7c-5p has been identified as a tumor suppressor in various malignancies; however, its function and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we explored the role and potential molecular mechanism of let-7c-5p in ESCC. mRNA and protein expression levels were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay was used to assess cell proliferation. Flow cytometry analysis was used to detect cell apoptosis, and cell migration was measured by wound healing assay and Transwell assays. The dual-luciferase reporter assay was used to verify the targeting relationship between let-7c-5p and CTHRC1. The tumor xenograft model was constructed to further verify the effect of let-7c-5p on the growth of ESCC in vivo. We found that let-7c-5p expression was downregulated in ESCC tissue and cell lines, and its reduced expression was correlated with TNM staging and lymph node metastasis. Next, we found that let-7c-5p can be used to discriminate ESCC patients from normal control subjects by receiver operating characteristic (ROC) curve analysis. Subsequently, we observed that let-7c-5p overexpression inhibited proliferation and migration and promoted apoptosis, while let-7c-5p down-regulation promoted proliferation and migration and inhibited apoptosis of TE-1 and KYSE150 cells. Furthermore, let-7c-5p overexpression inhibited tumor growth, while let-7c-5p inhibition promoted tumor growth in xenograft models. In addition, we confirmed that CTHRC1 was a direct target gene of let-7c-5p. Then, we found that let-7c-5p level was negatively correlated with CTHRC1 and negatively regulated expression of CTHRC1 in ESCC. Moreover, we confirmed that let-7c-5p upregulation significantly reduced the phosphorylation of AKT and ERK by directly inhibiting CTHRC1, while let-7c-5p downregulation showed the opposite effect. Our findings indicate that let-7c-5p is markedly downregulated in ESCC and suppresses proliferation and migration and promotes apoptosis of ESCC cells by inhibiting the AKT and ERK signaling pathways through negatively regulating CTHRC1. Therefore, these results suggest that let-7c-5p may represent a novel biomarker and therapeutic target for ESCC.
Journal of Traditional Chinese Medical Sciences, Volume 7, pp 337-344; https://doi.org/10.1016/j.jtcms.2020.10.002
The publisher has not yet granted permission to display this abstract.
Frontiers in Veterinary Science, Volume 7; https://doi.org/10.3389/fvets.2020.565773
Collagen triple helix repeat containing-1 (CTHRC1) has recently been identified as avian leukosis virus subgroup J (ALV-J) replication-dependent factor that remarkably facilitates ALV-J replication via interaction with the envelope glycoprotein (SU) of ALV-J. However, the dynamic distribution and localization of CTHRC1 in various tissues upon ALV-J infection are still unknown. In this study, data revealed that the levels of CTHRC1 were significantly increased in various tissues and that the protein was mainly located in the cytoplasm and nucleus of parenchymal cells in tissues of chickens that were infected by ALV-J naturally and experimentally. Interestingly, CTHRC1 was also observed in leukocytes other than erythrocytes in congested veins of ALV-J-infected tissues. Consequently, the positive cells in these veins were confirmed as lymphocytes by laser confocal microscopy. Taken together, these results conclude that the CTHRC1 is an inducible protein and exhibited ubiquitous expression in ALV-J-infected chickens, which may provide basic information for in-depth study of ALV-J infection and replication mechanisms.
International Journal of Dermatology, Volume 60, pp 661-671; https://doi.org/10.1111/ijd.15159
Journal of Translational Medicine, Volume 18, pp 1-18; https://doi.org/10.1186/s12967-020-02498-3
Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09–14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.
Matrix Biology, Volume 91-92, pp 109-116; https://doi.org/10.1016/j.matbio.2020.03.010
The publisher has not yet granted permission to display this abstract.
Cell Reports, Volume 31; https://doi.org/10.1016/j.celrep.2020.107597
Fibrosis and fat replacement in skeletal muscle are major complications that lead to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, the in vivo properties of adipogenic stem and precursor cells remain unclear, mainly due to the high cell heterogeneity in skeletal muscles. Here, we use single-cell RNA sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identify an interstitial CD142-positive cell population in mice and humans that is responsible for the inhibition of adipogenesis through GDF10 secretion. Furthermore, we show that the interstitial cell composition is completely altered in muscular dystrophy, with a near absence of CD142-positive cells. The identification of these adipo-regulatory cells in the skeletal muscle aids our understanding of the aberrant fat deposition in muscular dystrophy, paving the way for treatments that could counteract degeneration in patients with muscular dystrophy.
Infectious Agents and Cancer, Volume 15, pp 1-10; https://doi.org/10.1186/s13027-020-0278-x
Background: Genital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology was taken as a gold standard.Methods: Articles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA test (in terms of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2 + .Results: Out of 231 applicable citations, we have included 29 articles that included a total of 23,576 study participants (age range, 15–84 years) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6 and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of these three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, specificity 73%, PPV 70 and NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, specificity 46.2%, PPV 34.3% and NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, specificity 54.6%, PPV 54.3% and NPV was at 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8 and 90.9%.Conclusions: The reported diagnostic accuracy implies that HPV mRNA based tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.
Reproductive Biomedicine Online, Volume 40, pp 26-32; https://doi.org/10.1016/j.rbmo.2019.10.001
Endometriosis is characterized by the occurrence of endometrial-like tissue outside the uterus. Collagen triple helix repeat containing-1 (CTHRC1) is known as a tumour-promoting factor in several neoplasms. This study aimed to examine the roles of CTHRC1 in the development and progression of endometriosis, and to unravel the underlying mechanisms. Quantitative real-time PCR, western blot analyses and enzyme-linked immunosorbent assay were performed to determine the expression levels of CTHRC1 in tissues and serum. In addition, CTHRC1 expression levels were knocked down by small-interfering RNA in ectopic endometrial stromal cells (EESC). Cell Counting Kit-8, fluorescence-activated cell sorting, Transwell and wound scratch assays were carried out to assess the underlying biological behaviours, and western blot analyses were performed to reveal the molecular mechanisms. mRNA and protein expression levels of CTHRC1 were markedly higher in ectopic endometrial tissues than in eutopic and control endometrial tissues. In addition, the serum concentration of CTHRC1 was apparently higher in the endometriosis group than the control group. Small interfering RNA knockdown of CTHRC1 suppressed the proliferation, migration, invasion and healing abilities of EESC. Furthermore, the protein expressions of key molecules in the Wnt/β-catenin pathway showed an obvious down-regulated expression after siRNA transfection. These findings suggest that CTHRC1 may be partly responsible for the development and progression of endometriosis by increasing EESC proliferation, migration and invasion via the Wnt/β-catenin pathway. CTHRC1 may thus serve as a diagnostic and therapeutic target for endometriosis.
Published: 10 October 2019
Journal of Cancer Research and Clinical Oncology, Volume 146, pp 197-203; https://doi.org/10.1007/s00432-019-03043-6
Evidence from multiple clinical trials showed that local consolidative therapy (LCT) improved survival in oligometastatic non-small cell lung cancer (NSCLC) patients. In the present study, we aim to explore the potential role of microwave ablation (MWA) as LCT for epidermal growth factor receptor (EGFR)-mutant advanced NSCLC patients with extracranial oligometastasis.
Molecular Medicine Reports, Volume 20, pp 4244-4252; https://doi.org/10.3892/mmr.2019.10690
Collagen triple helix repeat containing 1 (CTHRC1) is a gene that has been associated with tumor progression in human prostate cancer (PC). The tumor immune microenvironment has been linked with disease outcome in PC. In the present study, the correlation between CTHRC1 with PC recurrence and the tumor immunological microenvironment was investigated. Using the data supplied by the Tumor Immune Estimation Resource (TIMER), the expression of CTHRC1, programmed cell death protein 1 (PD-1), and programmed cell death 1 ligand 1 (PD-L1) were analyzed. Immunohistochemical staining of CTHRC1, PD-1 and PD-L1 was performed using a tissue microarray construction of prostate adenocarcinoma (PRAD) specimens. In PRAD, an association was reported between the CTHRC1 expression and the disease free survival (DFS) rate (P=0.022). Overexpression of CTHRC1 was correlated with increased levels of PD-1 (R=0.272, P=0.021) and PD-L1 (R=0.298, P=0.016), elevated levels of infiltrating B cells (P=9.51e−11), CD4+ cells (P=1.51e−11), macrophages (P=8.25e−5), neutrophils (P=2.17e−9) and dendritic cells (P=3.13e−13). Bioinformatics analysis revealed that CTHRC1 was correlated with the expression levels of matrix metalloproteinase-9, mucin 1 and solute carrier organic anion transporter family member 2B1 genes, which exert an influence in PRAD. The occurrence of this condition is most likely to be associated with regulation of the tumor microenvironment. Taken together, we demonstrated that the prognosis and immunity of PC are closely linked to CTHRC1 upregulation. Furthermore, these results suggest that the immune function of PC may be suppressed by CTHRC1-targeting therapy.
Experimental Cell Research, Volume 381, pp 112-120; https://doi.org/10.1016/j.yexcr.2019.04.033
Cell adhesion and migration are key cell behaviours during gastrulation in early embryos and metastasis in cancers. Cthrc1 is a secreted protein highly conserved among vertebrates; it is upregulated in injured and diseased arteries, as well as in malignant cancers. There is increasing evidence showing that its expression and activity are associated with cancer progression and inflammatory diseases. However, the mechanism by which it regulates cell migration, and its implication during early development remains unclear. Here we show that zebrafish Cthrc1a is expressed in hypoblast cells, and is required for cell adhesion and migration during gastrulation. Knockdown of cthrc1a in whole embryo inhibits epiboly and convergent extension movements, and reduces the elongation of anteroposterior axis. Cell adhesion assay indicates that Cthrc1a is necessary for mesendoderm cells to interact with fibronectin-coated substratum, and to extend polarised cellular protrusions. Moreover, secreted Cthrc1a proteins diffuse efficiently between blastoderm cells and are recruited by neighbouring cells in an integrin-dependent manner. Consistently, there exists a functional interaction between Cthrc1a and integrin β1 in anteroposterior axis elongation. These results provide insight into the function of Cthrc1a in the regulation of cell adhesion and migration during embryonic axis elongation.
Virus Research, Volume 264, pp 32-39; https://doi.org/10.1016/j.virusres.2019.02.014
The lifecycle of avian leukosis virus subgroup J (ALV-J), a typical tumorigenic retrovirus, is highly dependent upon host cellular proteins. However, there have been few studies directed at uncovering the host proteins responsible for ALV-J replication, which could provide insights into new strategies for ALV-J prevention and control. Here, we used proteomics to identify the association of differential levels of collagen triple helix-repeat-containing 1 (CTHRC1) and with viral replication. Our results revealed that CTHRC1 was significantly upregulated in ALV-J-infected cells in vitro, and these findings were confirmed in vivo. Additionally, CTHRC1 overexpression facilitated ALV-J replication, whereas CTHRC1 knockdown suppressed this activity. Moreover, we found that ALV-J drove CTHRC1 translocation from the nucleus to the cytosol through interactions with the ALV-J envelope glycoprotein. These results revealed CTHRC1 as a shutting protein recruited by ALV-J to facilitate viral replication.
Cardiovascular and Interventional Radiology, Volume 42, pp 693-699; https://doi.org/10.1007/s00270-018-02153-x
Most epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs) experience oligoprogressive disease. Local ablation for isolated resistant sites continued with the original EGFR-TKI showed good efficacy in these patients. We conducted this multicenter retrospective study to investigate the potential benefit of thermal ablation in NSCLC patients that developed extra-central nervous system (CNS) oligoprogressive disease during TKI treatment.