Systematic analyzing a five- miRNA panel and its diagnostic value of plasma expression in colorectal cancer.

BACKGROUND: Aberrant expression of miRNAs have been implicated in cancers, but the role of miRNAs in colorectal cancer (CRC) remains need to be elucidated. This study aimed to identify miRNAs that related to colorectal cancer (CRC) pathogenesis and determine the diagnostic value. METHODS: Three GEO datasets (GSE128449, GSE35602 and GSE49246) with 131 samples were used to screen miRNAs that differential expression between tumor and control tissues. The expression of the identified miRNAs was validated in 50 clinical tissue samples and the GSE35834 dataset. The clinical significance of these miRNAs was analyzed in the TCGA dataset and clinical tissue samples. The expression of miRNAs in tissues and plasma samples were tested by RT-PCR assay in clinical samples, and their diagnostic value was determined. RESULTS: The analysis of three GEO datasets revealed that miR-595 and miR-1237 were upregulated, while miR-126, miR-139, and miR-143 were downregulated in CRC tissues compared to control tissues. The differential expression of the five miRNAs in CRC tissues was confirmed using clinical tissue samples and GEO databases. There was no significant correlation between the TNM stage and tumor stage of CRC and any of the five miRNAs. Plasma expression of the miRNAs differed significantly between CRC and non-cancer patients, and each miRNA had moderate diagnostic value for CRC. Combining the five miRNAs provided better diagnostic potential for CRC than a single miRNA. CONCLUSIONS: This study demonstrated that five miRNAs were related to the pathogenesis of CRC, but independent of the stage of CRC; Plasma expression of these miRNAs have moderate diagnostic value, and combination of these miRNAs showed better diagnostic ability in CRC.

Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease. METHODS: Plasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA. RESULTS: The levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902-0.938) or HSP90α (AUC 0.836, 95%CI 0.810-0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925-0.957) significantly improved the diagnostic efficiency for HCC patients. CONCLUSION: The results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

Chemodynamic PtMn Nanocubes for Effective Photothermal ROS Storm a Key Anti-Tumor Therapy in-vivo.

Background: Chemodynamic therapy (CDT) is a new treatment approach that is triggered by endogenous stimuli in specific intracellular conditions for generating hydroxyl radicals. However, the efficiency of CDT is severely limited by Fenton reaction agents and harsh reaction conditions. Methods: Bimetallic PtMn nanocubes were rationally designed and simply synthesized through a one-step high-temperature pyrolysis process by controlling both the nucleation process and the subsequent crystal growth stage. The polyethylene glycol was modified to enhance biocompatibility. Results: Benefiting from the alloying of Pt nanocubes with Mn doping, the structure of the electron cloud has changed, resulting in different degrees of the shift in electron binding energy, resulting in the increasing of Fenton reaction activity. The PtMn nanocubes could catalyze endogenous hydrogen peroxide to toxic hydroxyl radicals in mild acid. Meanwhile, the intrinsic glutathione (GSH) depletion activity of PtMn nanocubes consumed GSH with the assistance of Mn3+/Mn2+. Upon 808 nm laser irradiation, mild temperature due to the surface plasmon resonance effect of Pt metal can also enhance the Fenton reaction. Conclusion: PtMn nanocubes can not only destroy the antioxidant system via efficient reactive oxygen species generation and continuous GSH consumption but also propose the photothermal effect of noble metal for enhanced Fenton reaction activity.

Rational designed Fe-ZIFs@CoP nanoplatforms for photothermal-enhanced ROS-mediated tumor therapy.

Metal-organic frameworks (MOFs), with biocompatible and bio-friendly properties, exhibit intriguing potential for the drug delivery system and imaging-guided synergistic cancer theranostics. Even though tremendous attention has been attracted on MOFs-based therapeutics, which play a crucial role in therapeutic drugs, gene, and biomedical agents delivery of cancer therapy, they are often explored as simple nanocarriers without further "intelligent" functions. Herein, Fe-doped MOFs with CoP nanoparticles loading were rationally designed and synthesized for photothermal enhanced reactive oxygen species (ROS)-mediated treatment. Fe-ZIFs@CoP could generate efficient ROS through the Fenton reaction while depleting glutathione for amplifying oxidative stress. Particularly, due to the photothermal effect of Fe-ZIFs@CoP, the hyperthermia generated by as-synthesized Fe-ZIFs@CoP facilitated the advanced performance of the Fenton effect for a high amount of ROS generation. The promising "all-in-one" synergistic MOFs platform herein reported provides some prospects for future directions in this area.

Prussian Blue-Derived Nanocomposite Synergized with Calcium Overload for Three-Mode ROS Outbreak Generation to Enhance Oncotherapy.

Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within tumor cells, simplistic calcium overloads do not allow for an effective antitumor therapy. Hence, the nanoparticles are created with polyethylene glycol (PEG) donor-modified calcium phosphate (CaP)-coated, manganese-doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP-PEG (GMCP). GMCP with a three-mode enhancement of intratumor reactive oxygen species (ROS) levels is designed to increase the efficiency of the intracellular calcium overload in tumor cells to enhance its anticancer efficacy. The released exogenous Ca2+ and the production of cytotoxic ROS resulting from the perfect circulation of the three-mode ROS outbreak generation that Fenton/Fenton-like reaction and consumption of glutathione from Fe2+/Fe3+and Mn2+/Mn3+ circle, and amelioration of hypoxia from MMPB-guided and GOx-mediated starvation therapy. Photothermal efficacy-induced heat generation owing to MMPB accelerates the above reactions. Furthermore, abundant ROS contribute to damage to mitochondria, and the calcium channels of efflux Ca2+ are inhibited, resulting in a calcium overload. Calcium overload further increases ROS levels and promotes apoptosis of tumor cells to achieve excellent therapy.

Methylation characteristics and developmental potential of Guangxi Bama minipig (Sus scrofa domestica) cloned embryos from donor cells treated with trichostatin A and 5-aza-2'-deoxycytidine.

Summary Reprogramming of DNA methylation in somatic cell nuclear transfer (SCNT) embryos is incomplete, and aberrant DNA methylation patterns are related to the inefficiency of SCNT. To facilitate nuclear reprogramming, this study investigated the effect of treating Guangxi Bama minipig donor cells with trichostatin A (TSA), 5-aza-2'-deoxycytine (5-aza-dC), or combination of TSA and 5-aza-dC prior to nuclear transfer. Analyses showed that there were no major changes in cell-cycle status among all groups. We monitored the transcription of DNMT1, DNMT3a, HDAC1 and IGF2 genes in donor cells. Transcription levels of HDAC1 were decreased significantly after treatment with a combination of TSA and 5-aza-dC, along with a significantly increased level of IGF2 (P < 0.05). Although treatment of donor cells with either TSA or 5-aza-dC alone resulted in non-significant effects in blastocyst formation rate and DNA methylation levels, a combination of TSA and 5-aza-dC significantly improved the development rates of minipig SCNT embryos to blastocyst (25.6% vs. 16.0%, P < 0.05). This change was accompanied by decreased levels of DNA methylation in somatic cells and blastocyst (P < 0.05). Thus in combination with TSA, lower concentrations of 5-aza-dC may produce a potent demethylating activity, and lead to the significantly enhanced blastocyst development percentage of Bama minipig SCNT embryos.

Exosomal miR-99b-5p Secreted from Mesenchymal Stem Cells Can Retard the Progression of Colorectal Cancer by Targeting FGFR3.

Human bone marrow mesenchymal stem cells (BMSCs) are efficient mass producers of exosomes that can potentially be utilized for delivery of miRNAs in cancer therapy. The current study aimed to assess the role of MSC-exosomal miR-99b-5p during the development of colorectal cancer (CRC). The potential value of using plasma levels of exosomal miR-99b-5p for predicting the liver metastasis of colorectal cancer was also assessed. In this study, we found that overexpression of fibroblast growth factor receptor 3 (FGFR3) was associated with tumor progression in CRC and FGFR3 was the target gene of miR-99b-5p, which was down-regulated in CRC tissues. Furthermore, we observed that elevated miR-99b-5p inhibited CRC cell proliferation, invasion and migration, while reduced levels had the opposite effect on CRC cells. Moreover, exosomal miR-99b-5p delivered by BMSCs was able to limit the proliferation, invasion and migration of CRC cells in vitro, as well as suppressing tumor growth in vivo. Collectively, these findings revealed that MSC-derived exosomal miR-99b-5p can be transferred into CRC cells and which can suppress tumor progression by targeting FGFR3. This highlights the potential of using exosomal miR-99b-5p as a novel diagnostic marker for CRC, while providing a therapeutic target to combat CRC.

Role of Serum CYFRA 21-1 in Diagnosis and Prognostic in Colorectal Liver Metastases.

Purpose: In current studies, the role of serum Cytokeratin-19 fragments (CYFRA 21-1) in colorectal cancer (CRC) remains unclear. This study aimed to clarify the diagnostic and prognostic value of CYFRA 21-1 in CRC. Patients and Methods: Data were collected for 196 stage I-III CRC patients and 50 colorectal liver metastases (CRLM) patients between January 2018 and December 2019. The serum CYFRA 21-1 levels were measured using the chemiluminescent particle immunoassay (CMIA) kit in all objects and common biomarkers such as CA19-9, CEA, HSP90α, and AFP were measured in all colorectal cancer patients. We investigated the association between CYFRA 21-1 level and clinicopathological features. In addition, we evaluated the ability of serum CRFRA21-1 to differentiate CRLM from CRC. To assess the potential prognostic value, we used Cox proportional hazard model for univariate or multivariate analyses. Results: Serum CYFRA 21-1 was significantly elevated in CRLM patients compared to stage I-III CRC patients (5.85 ng/mL vs 2.29 ng/mL, p < 0.001). For all CRC patients cohort, stage I-III CRC patients cohort and CRLM patients cohort, the optimal cutoff levels of CYFRA 21-1 for overall survival (OS) were 3.47 ng/mL, 2.14 ng/mL and 7.63 ng/mL, respectively, and the optimal cutoff levels for progression-free survival (PFS) were 3.47 ng/mL, 2.56 ng/mL and 7.63 ng/mL, respectively. For CRLM patients, Kaplan-Meier analysis showed that patients with high CYFRA 21-1 level had poor OS. Multivariate analysis indicated that the CYFRA 21-1 level was an independent prognostic factor for PFS in stage I-III patients. And CYFRA 21-1 levels and age were independent prognostic factors for OS and PFS in CRLM patients. Conclusion: CYFRA 21-1 can better differentiate CRLM patients from the whole CRC patients and has unique prognostic value for CRLM patients.

The critical role of serum thymidine kinase 1(STK1) in predicting prognosis for immunotherapy in T4 stage lung squamous cell carcinoma.

Purpose: The role of serum thymidine kinase 1 (STK1) in predicting the prognosis of T4-stage lung squamous cell carcinoma (LUSC) with immunotherapy is the focus of our work. Methods: A total of 180 LUSC patients were enrolled. In this study, according to the T stage, the patients were divided into two groups: the T1-T2 stage and the T3-T4 stage. Receiver operating characteristic (ROC) curves were used to determine the best cutoff value for predicting overall survival (OS) outcomes. The next step is to use this cutoff value to introduce univariate and multivariate Cox regression models to screen the prognostic factors in different T stages of LUSC. The association of STK1 with other clinicopathological factors was also determined. Finally, to further explore the link between STK1 and the staging of LUSC patients, we have further divided the staging into T1-3 and T4 stages. We identified factors influencing the prognosis of patients who received immunotherapy in T4 stage LUSC. Results: First, we determined that the optimal cutoff for STK1 for predicting OS outcome was 1.165 pmol/L. Correlation analysis revealed that STK1 was over-expressed in LUSC patients at the T3-4 stage. Univariate and multivariate analysis showed that immunotherapy was an independent prognostic factor in patients with T4 stage LUSC. In the group of patients who received immunotherapy or not, the STK1 expression level was found to be an independent prognostic factor in T4 LUSC patients receiving PD-1/PD-L1 inhibitor treatment; patients with high levels of STK1 had an increased risk of death (95%CI = 1.028-2.04). Conclusion: STK1 is associated with a higher T stage and may be an effective prognostic marker for advanced LUSC immunotherapy patients.

Corrigendum: Tailoring mSiO2-SmCox nanoplatforms for magnetic/photothermal effect-induced hyperthermia therapy.

[This corrects the article DOI: 10.3389/fbioe.2023.1249775.].

Tailoring mSiO2-SmCox nanoplatforms for magnetic/photothermal effect-induced hyperthermia therapy.

Hyperthermia therapy is a hotspot because of its minimally invasive treatment process and strong targeting effect. Herein, a synergistic magnetic and photothermal therapeutic nanoplatform is rationally constructed. The well-dispersive mSiO2-SmCox nanoparticles (NPs) were synthesized through a one-step procedure with the regulated theoretical molar ratio of Sm/Co among 1:1, 1:2, and 1:4 for controlling the dispersion and magnetism properties of SmCox NPs in situ growth in the pore structure of mesoporous SiO2 (mSiO2), where mSiO2 with diverse porous structures and high specific surface areas serving for locating the permanent magnetic SmCox NPs. The mSiO2-SmCox (Sm/Co = 1:2) NPs with highly dispersed and uniform morphology has an average diameter of ∼73.08 nm. The photothermal conversion efficiency of mSiO2-SmCox (Sm/Co = 1:2) NPs was determined to be nearly 41%. The further in vitro and in vivo anti-tumor evaluation of mSiO2-SmCox (Sm/Co = 1:2) NPs present promising potentials for hyperthermia-induced tumor therapy due to magnetic and photothermal effects.

GSH-Triggered/Photothermal-Enhanced H2S Signaling Molecule Release for Gas Therapy.

Traditional treatment methods for tumors are inefficient and have severe side effects. At present, new therapeutic methods such as phototherapy, chemodynamic therapy, and gasodynamic therapy have been innovatively developed. High concentrations of hydrogen sulfide (H2S) gas exhibit cancer-suppressive effects. Herein, a Prussian blue-loaded tetra-sulfide modified dendritic mesoporous organosilica (PB@DMOS) was rationally constructed with glutathione (GSH)-triggered/photothermal-enhanced H2S signaling molecule release properties for gas therapy. The as-synthesized nanoplatform confined PB nanoparticles in the mesoporous structure of organosilica silica due to electrostatic adsorption. In the case of a GSH overexpressed tumor microenvironment, H2S gas was controllably released. And the temperature increases due to the photothermal effects of PB nanoparticles, further enhancing H2S release. At the same time, PB nanoparticles with excellent hydrogen peroxide catalytic performance also amplified the efficiency of tumor therapy. Thus, a collective nanoplatform with gas therapy/photothermal therapy/catalytic therapy functionalities shows potential promise in terms of efficient tumor therapy.

PdMo nanoflowers for endogenous/exogenous-stimulated nanocatalytic therapy.

The clinical application of reactive oxygen species (ROS)-mediated tumor treatment has been critically limited by inefficient ROS generation. Herein, we rationally synthesized and constructed the three-dimensional PdMo nanoflowers through a one-pot solvothermal reduction method for elaborately regulated peroxidase-like enzymatic activity and glutathione peroxidase-like enzymatic activity, to promote oxidation ROS evolvement and antioxidation glutathione depletion for achieving intensive ROS-mediated tumor therapy. The three-dimensional superstructure composed of two-dimensional nanosheet subunits can solve the issues by avoiding the appearance of tightly stacked crystalline nanostructures. Significantly, Mo is chosen as a second metal to alloy with Pd because of its more chemical valence and negative ionization energy than Pd for improved electron transfer efficiencies and enhanced enzyme-like activities. In addition, the photothermal effect generated by PdMo nanoflowers could also enhance its enzymatic activities. Thus, this work provides a promising paradigm for achieving highly ROS-mediated tumor therapeutic efficacy by regulating the multi-enzymatic activities of Pd-based nanoalloys.

[Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, P< 0.05). However, neither in PZM-3 nor in HECM-10, 2-10 mmol/L VPA treatment did not increase the in vitro developmental potential of iSCNT embryos. It was concluded that TSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

High Expression of Plasma Extracellular HSP90α is Associated With the Poor Efficacy of Chemotherapy and Prognosis in Small Cell Lung Cancer.

Purpose: eHSP90α is closely related to tumor progression and prognosis. This study aimed to investigate the significance of eHSP90α in the response evaluation and prediction of small cell lung cancer. Methods: We analyzed the relationship between eHSP90α expression and clinicopathological features in 105 patients with small cell lung cancer. Univariate and multivariate analyses were used to determine the association of parameters and ratios with response assessment, progression-free survival (PFS), and overall survival (OS). Results: In SCLC patients, eHSP90α and NSE were positively correlated. The cutoff values of eHSP90α in OS, PFS, and response evaluation were 61.2 ng/ml, 48.7 ng/ml, and 48.7 ng/ml, respectively. eHSP90α could better predict OS, PFS, and response evaluation (AUC OS 0.791, PFS 0.662, 0.685). Radiotherapy and eHSP90α were independent variables for effective chemotherapy through univariate and multivariate analysis. In contrast, radiotherapy, eHSP90α, NSE, and M stage were independent variables for OS. eHSP90α, and M stage were independent variables for PFS. Kaplan-Meier analysis showed that higher eHSP90α expression predicted poorer OS and earlier progression in patients. Conclusions: This study aims to provide new evidence for the efficacy response and prognostic assessment of SCLC. eHSP90α may be a better biomarker for SCLC.

The High Ratio of the Plasma miR-96/miR-99b Correlated With Poor Prognosis in Patients With Metastatic Colorectal Cancer.

Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value. Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules. Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values. Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.

Prognostic Value of C-Reactive Protein, Glasgow Prognostic Score, and C-Reactive Protein-to-Albumin Ratio in Colorectal Cancer.

Background: Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC. Methods: Overall, 307 stage I-III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019. We investigated the correlation between the pretreatment CRP, GPS, and CAR and the clinicopathological characteristics. The Cox proportional hazards model was used for univariate or multivariate analysis to assess potential prognostic factors. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of each prognostic score. We established CRC survival nomograms based on the prognostic scores of inflammation. Results: The optimal cutoff levels for the CAR for overall survival (OS) in all CRC patients, stage I-III CRC patients, and CRLM patients were 0.16, 0.14, and 0.25, respectively. Kaplan-Meier analysis and log-rank tests demonstrated that patients with high CRP, CAR, and GPS had poorer OS in CRC, both in the cohorts of stage I-III patients and CRLM patients. In the different cohorts of CRC patients, the area under the ROC curve (AUC) of these three markers were all high. Multivariate analysis indicated that the location of the primary tumor, pathological differentiation, and pretreatment carcinoembryonic antigen (CEA), CRP, GPS, and CAR were independent prognostic factors for OS in stage I-III patients and that CRP, GPS, and CAR were independent prognostic factors for OS in CRLM patients. The predictors in the prediction nomograms included the pretreatment CRP, GPS, and CAR. Conclusions: CRP, GPS, and CAR have independent prognostic values in patients with CRC. Furthermore, the survival nomograms based on CRP, GPS, and CAR can provide more valuable clinical significance.

Plasma HSP90AA1 Predicts the Risk of Breast Cancer Onset and Distant Metastasis.

AIM: We aimed to develop and validate a comprehensive nomogram containing pre-treatment plasma HSP90AA1 to predict the risk of breast cancer onset and metastasis. METHODS: We assessed the expression of HSP90s in breast cancer patients using an online database. To verify the results, 677 patients diagnosed with breast cancer and 146 patients with benign breast disease between 2014 and 2019 were selected from our hospital and were divided into cancer risk and metastasis risk cohorts. We focused on HSP90AA1 to elucidate the risks of onset and metastasis in the cohorts. RESULTS: Expression levels of HSP90AA1, HSP90AA2, HSP90AB1, HSP90B1, and TRAP1 were linked to disease progression. Survival analysis using the GEPIA and OncoLnc databases indicated that the upregulation of HSP90AA1 and HSP90AB1 was related to poor overall survival. In the cancer risk cohort, carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), HSP90AA1, T cells%, natural killer cells%, B cells%, neutrophil count, monocyte count, and d-dimer were incorporated into the nomogram. A high Harrell's concordance index (C-index) value of 0.771 [95% confidence interval (CI), 0.725-0.817] could still be reached in the interval validation. In the metastasis risk cohort, predictors contained in the prediction nomogram included the use of CEA, CA153, HSP90AA1, carbohydrate antigen 125 (CA125), natural killer cells%, B cells%, platelet count, monocyte count, and d-dimer. The C-index was 0.844 (95% CI, 0.801-0.887) and it was well-calibrated. HSP90AA1 raised net clinical benefit of breast cancer onset and metastasis risk prediction nomogram in a range of risk thresholds (5-92%) and (1-90%). CONCLUSION: Our study revealed that pretreatment plasma HSP90AA1 combined with other markers could conveniently predict the risk of breast cancer onset and metastasis.

Plasma Levels of Heat Shock Protein 90 Alpha Associated With Colorectal Cancer Development.

Aim: The role of plasma heat shock protein 90 alpha (HSP90α) in colorectal cancer patients remains unclear. This study aimed to evaluate the relationship between HSP90α and the occurrence and development of colorectal cancer through diagnosis and prognosis value. Methods: 635 colorectal cancer patients and 295 healthy controls were recruited. The HSP90α was measured by using the ELISA kit in all objects and the immune cells and common biomarkers as CEA, AFP, CA125, CA153 and CA199 were measured in all colorectal cancer patients. The relationship between plasma HSP90α with clinical features, common tumor markers and immune cells were also conducted. The survival analysis endpoint was progression-free survival (PFS). Results: The levels of plasma HSP90α were significantly higher in colorectal cancer patients compared to healthy controls [51.4 (ng/ml) vs. 43.7 (ng/ml), p < 0.001]. In additional, the levels of plasma HSP90α were associated with gender and disease progress as stage, lymphatic and distant metastasis. Furthermore, plasma HSP90α was closed correlation with CEA, CA125, CA199 and percentage of B cells. However, the initial expression level of plasma HSP90α failed to show a prognostic value for progression-free survival in colorectal cancer. Conclusion: The plasma Hsp90α was remarkable higher in colorectal cancer and correlated with common tumor biomarkers and immune cells. Plasma Hsp90α levels were associated with disease progress but a poor diagnosis performance and also failed to show a prognostic value in colorectal cancer.

miR-155, miR-96 and miR-99a as potential diagnostic and prognostic tools for the clinical management of hepatocellular carcinoma.

Increasing evidence has demonstrated that circulating microRNAs (miRNAs) can be utilized as potential biomarkers for the diagnosis of cancer, as well as a prognostic tool for the management of the disease. Therefore, the present study aimed to evaluate the predictive ability of miRNA (miR)-155, miR-96 and miR-99a for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Tissues were collected from 30 patients with HCC and their matched adjacent normal liver tissues, as well as from serum samples from 30 patients with HCC and 30 healthy controls. Reverse transcription-quantitative PCR was used to measure the expression levels of miR-155, miR-96 and miR-99a. The expression levels of miR-155 and miR-96 were upregulated in the tissues and serum of patients with HCC, whereas miR-99a expression levels were decreased. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-155, miR-96, miR-99a and a combination of these three miRNAs could serve as diagnostic biomarkers for HCC with areas under the curve (AUC) of 0.84, 0.824, 0.799 and 0.931, respectively. Serum α-fetoprotein (AFP) was detected using electrochemiluminescence immunoassay analyzer. The addition of AFP with the combination of these three miRNAs offered a higher accuracy of HCC diagnosis (AUC, 0.979; sensitivity, 90.0%; specificity, 100.0%). In addition, elevated expression levels of miR-155 and miR-96 were associated with poor survival time of patients with HCC. The panel of miR-155, miR-96, miR-99a and AFP had a higher sensitivity and specificity for the diagnosis of HCC when compared with a single marker. Furthermore, the present data suggested that miR-155 and miR-96 may be potential prognostic markers for the clinical management of patients with HCC.