Development of risk prediction models for lung cancer based on tumor markers and radiological signs

BackgroundAccurate prediction of malignancy risk for pulmonary lesions with pleural effusion improves early diagnosis of lung cancer. This study aimed to develop and validate a model to predict lung cancer.MethodsClinical data of 536 patients with pulmonary diseases were collected. The risk factors were identified by regression analysis. Three prediction models were developed. The predictive performances of the models were measured by the area under the curves (AUCs) and calibrated with 1000 bootstrap samples to minimize the over‐fitting bias. The net benefits of the models were evaluated by decision curve analysis. Finally, a separate cohort of 134 patients was used to validate the models externally.ResultsSeven independent risk factors were identified from 18 clinical variables, which included the pleural fluid carcinoembryonic antigen (CEA), serum cytokeratin‐19 fragment (CYFRA 21‐1), the ratio of CEA in the pleural fluid to serum, extrathoracic cancer history (>5 years), tumor size, vessel convergence, and lobulation. The AUCs of the three models were 0.976, 0.927, and 0.944 in the training set and 0.930, 0.845, and 0.944 in the external set, respectively. The accuracies of the three models were 89.6%, 81.4%, and 88.8%. Model 1 showed the best iteration fit (R ² = 0.84, 0.68, and 0.73) and a higher net benefit on decision curve analysis when compared to the other two models.ConclusionThe advantageous model could assess the risk of lung cancer in patients with pleural effusion and act as a useful tool for early identification of lung cancer.     

Application of collagen triple helix repeat containing‐1 and mitotic spindle apparatus antibody in small cell lung cancer diagnosis

BackgroundThe clinical significance of serum collagen triple helix repeat protein‐1 (CTHRC1) and mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).MethodsOf the 229 lung tumor patients selected, 62 patients were divided into SCLC, 94 patients with non‐small cell lung cancer (NSCLC), and 73 patients with benign lung disease (BLD). The health controls (HC) had a span of 66 cases with normal physical condition. The serum extracted from each participator and enzyme‐linked immunosorbent assay was adopted for measuring the serum CTHRC1 and MSA; in the meantime, automatic electrochemiluminescence immunoassay was used for the quantitative determination of serum NSA and CEA. And then, the differences in serum CTHRC1, MSA, NSE, and CEA were compared among involved groups.Results① Compared with other groups, the concentrations of CTHRC1, MSA, and NSE showed a marked increase in the group of SCLC (all p < 0.01). Especially for SCLC patients with lymph node metastasis, CTHRC1 provided a notably higher level than those without metastasis. ② CTHRC1 and MSA established a diagnostic criterion with the specificity of 90.99% and 86.27% for SCLC, respectively. ③ In series, the specificity of CTHRC1 and NSE was the highest (99.30%), while MSA and NSE had the highest sensitivity (96.72%) in parallel. ④ Both CTHRC1 and MSA were hazardous factors interconnected with SCLC.ConclusionSerum CTHRC1 and MSA had a more exciting prospect of application. When used in conjunction with NSE and CEA, they could optimize the clinical diagnosis value of SCLC.     

Serum Circ‐FAF1/Circ‐ELP3: A novel potential biomarker for breast cancer diagnosis

BackgroundRecently, measurement of serum circular RNAs (circRNAs) as a non‐invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ‐ELP3 and Circ‐FAF1, separately and simultaneously, for diagnosis of patients with breast cancer.MethodsSeventy‐eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined.ResultsCompared to non‐cancerous controls, Circ‐ELP3 was upregulated in breast cancer patients (p‐value = 0.004). On the other hand, serum Circ‐FAF1 was seen to be decreased in breast cancer patients than controls (p‐value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ‐ELP3 and Circ‐FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ‐ELP3 and Circ‐FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively.ConclusionBriefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ‐ELP3 and Circ‐FAF1 as a non‐invasive marker, in detection of breast carcinomas.     

Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

ObjectiveThe purpose of this study was to analyze the levels of tumor‐associated autoantibodies (TAAbs) in lung diseases and determine their diagnostic efficiency in early‐stage non‐small cell lung cancer (NSCLC).MethodsWe retrospectively analyzed the levels of 7‐TAAbs in 177 newly diagnosed early‐stage NSCLC patients, 202 patients with lung benign diseases and 137 healthy cases. The levels of a panel of 7‐TAAbs, including p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4‐5, were measured by ELISA.ResultsThe serum levels of p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, and GBU4‐5 were not statistically different among NSCLC, benign and healthy groups (p > 0.05). The area under the curve (AUC) of 7‐TAAbs was all lower than 0.70. The sensitivity of combined detection was the highest (23.73%), while the specificity was the lowest (88.79%). The positive rates of PGP9.5, SOX2, and combined detection were significantly different among the three groups (p < 0.05). Among them, PGP9.5 and combined detection were significantly different between the NSCLC and benign groups (p < 0.05), PGP9.5, SOX2 and combined detection were significantly different between the NSCLC and healthy groups (p < 0.05).ConclusionsThe diagnostic efficiency of 7‐TAAbs in early‐stage NSCLC was not high, so it cannot be used alone as a screening method for NSCLC.     

Identification and validation of PGLS as a metabolic target for early screening and prognostic monitoring of gastric cancer

BackgroundGastric cancer is the third leading cause of cancer‐related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6‐phosphogluconolactonase (PGLS) in gastric cancer.MethodsThe protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8‐plex) reagents, and followed by LC‐ESI‐MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan‐Meier plotter database.ResultsThe present study found that PGLS was significantly up‐regulated in gastric cancer by using iTRAQ‐based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post‐progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e‐05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her‐2 (‐).ConclusionsThese findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post‐progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow‐up monitoring for gastric cancer.     

Diagnostic accuracy of the cancer ratio for the prediction of malignant pleural effusion: evidence from a validation study and meta-analysis

ObjectiveThis study aimed to assess the diagnostic accuracy of serum LDH to pleural ADA ratio (cancer ratio, CR)for malignant pleural effusion (MPE) through an original study and meta-analysis.MethodsWe retrospectively collected data from 145 patients with MPE and 117 cases of benign pleural effusions (BPE). The diagnostic performance of CR and a typical biomarker of MPE, carcinoembryonic antigen (CEA), were analysed using the receiver operating characteristic (ROC) curves and the area under the curve (AUC) as a measure of accuracy. The overall diagnostic accuracy of CR was summarised by a standard diagnostic meta-analysis.ResultsSignificantly higher CR and pleural CEA values were observed in the MPE patients than in the BPE patients. At a cut-off value of 14.97, CR showed high sensitivity (0.91), low specificity (0.67), and high AUC (0.85). The combination of CEA and CR increased the AUC to 0.98. The meta-analysis included seven studies involving 2,078 patients. The pooled values for sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of CR were 0.96, 0.88, 7.70, 0.05, and 169, respectively. The AUC of the summary ROC of CR was 0.98.ConclusionCR has a high diagnostic accuracy for predicting MPE, especially when used in combination with pleural CEA.     

Diagnosis value of miR‐181, miR‐652, and CA72‐4 for gastric cancer

PurposeTo find a useful disease marker for early diagnosis of gastric cancer, we tried to explore the expression of serum miR‐181, miR‐652, and carbohydrate antigen 72‐4 (CA72‐4).Patients and MethodsAccording to clinical pathologic stages, 112 patients with gastric cancer were divided into early gastric cancer group (n = 60) and advanced gastric cancer group (n = 52), stage I‐II (n = 65), and stage III‐IV (n = 47). Another 50 cases of gastric benign lesions and 40 healthy controls were also selected. Real‐time quantitative PCR together with chemiluminescence were applied to detect expression levels. ROC curve was applied to judge their diagnostic efficiency. Pearson''s correlation analysis was put into use to investigate the relevance of three indicators.ResultsCompared with benign lesions group and control group, significantly higher expression levels were found in patients of gastric cancer (all p < 0.001). Similarly, compared with early gastric cancer group, significantly higher expression levels were found in advanced gastric cancer group (all p < 0.001). The same result was also found in stage III‐IV (all p < 0.001). The best cutoff values were 0.93, 2.38, and 16.94 U/ml, respectively. The area under the curve (0.917, 95%CI: 0.856–0.975) of the three combined diagnosis of early gastric cancer was the largest, and its sensitivity and specificity were 92.5% and 86.8%. And miR‐181 and miR‐652 were positively correlated with CA72‐4 (r = 0.772, p < 0.001, r = 0.853, p < 0.001).ConclusionSerum miR‐181, miR‐652, and CA72‐4 are closely linked to the occurrence and development of gastric cancer. Combination of three indicators has diagnostic value for early gastric cancer.     

Serum transfer RNA‐derived fragment tRF‐31‐79MP9P9NH57SD acts as a novel diagnostic biomarker for non‐small cell lung cancer

BackgroundtRNA‐derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non‐small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF‐31‐79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.MethodsBy using stem‐loop quantitative real‐time PCR, we were able to detect various tRF‐31‐79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre‐ and post‐surgery (qRT‐PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.ResultsSerum tRF‐31‐79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF‐31‐79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF‐31‐79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.Conclusionserum tRF‐31‐79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.     

Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal cancer

BackgroundNowadays, non‐invasive and rapid detection of cancers through molecular biomarkers has received much attention. Therefore, this study investigated the non‐invasive and rapid diagnosis of colorectal cancer through one of the newest biomarkers (circular RNA).MethodsFor this purpose, we collected tumoral, adjacent normal tissue, and plasma samples from 100 colorectal cancer (CRC) patients, 25 postoperative CRC patients, 28 colitis patients, and 108 healthy donors. First Illumina high‐throughput (Hi Seq 2000) sequencing was performed to identify known and novel differentially expressed circRNAs in the cancerous and adjacent normal tissues (n = 3). We used quantitative real‐time fluorescent polymerase chain reaction (qRT‐PCR) to detect the expression level of hsa_circ_0006282 among the different samples. Moreover, inter‐ and intra‐assays were performed to evaluate the potential of hsa_circ_0006282 as being a biomarker. The receiver operating characteristic curve (ROC) was drawn to appraise its diagnostic efficacy, and the sensitivity of this circ RNA was evaluated.ResultsBased on RNA‐sequencing results circ_0006282, cirs7, circ‐0001313, circ_0055625, circ_000984, circ_0055625, circ_0001178, circ_0071589, circ‐001569 were upregulated, and circ‐ITGA7, circ‐CDYL, circITCH, circ_0026344, circ_0000038, circ_0002220, circ_0067480, circIGHV3‐20‐1, circ_104916, circ_0009361 were downregulated circRNA. The hsa_circ_0006282 was the highest upregulated differentially expressed circRNA. Expression evaluation of this circRNA on different samples showed upregulation in CRC tissues (p < 0.0001) and plasma samples of CRC patients in comparison to healthy controls (p < 0.0001), while the area under the curve (AUC) was 0.831 (95% CI: 0.779–0.883). Expression of hsa_circ_0006282 in CRC patients decreased to normal after surgery (p < 0.0001). Our results showed high specificity and sensitivity of CRC detection when hsa_circ_0006282, carcinoembryonic antigen (CEA), and carbohydrate antigen199 (CA199) are combined.ConclusionPlasma hsa_circ_0006282 can be used as a novel diagnostic and dynamic monitoring biomarker in CRC patients.     

A panel of three serum microRNA can be used as potential diagnostic biomarkers for nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma is cancer with unique epidemiological characteristics, showing obvious ethnicity, gender, and geographical prevalence. More and more evidence shows that microRNAs are stable in serum and are specific to different tumor types. Therefore, miRNA is a new non‐invasive biomarker for cancer detection.MethodsThe experiment is divided into three stages, namely, the screening stage, the training stage, and the verification stage. We took 54 patients with nasopharyngeal carcinoma and 108 healthy controls as the research objects. We use the receiver‐operating characteristic (ROC) curve and area under the ROC curve (AUC) to evaluate the diagnostic value of miRNA. Finally, a three‐miRNA panel with high diagnostic efficiency was constructed. In addition, we conducted biological information analysis of these miRNAs to explore their functions.ResultsIn NPC patients, the expression of five serum miRNAs (miR‐29c‐3p, miR‐143‐5p, miR‐150‐5p, miR‐145‐3p, and miR‐205‐5p) is significantly dysregulated. Among them, the diagnostic value of these three miRNAs (miR‐29c‐3p, AUC = 0.702; miR‐143‐5p, AUC = 0.733; and miR‐205‐5p, AUC = 787) is more prominent. The diagnostic panel constructed by them has a higher diagnostic value (AUC = 0.902). Through the analysis of the TCGA data set, the target gene of the three‐miRNA panel may be KLF7, NRG1, SH3BGRL2, and SYNPO2.ConclusionThe three‐miRNA panel (miR‐29c‐3p, miR‐143‐5p, and miR‐205‐5p) may become a novel non‐invasive biological marker for nasopharyngeal cancer screening.     

MALDI‐TOF‐MS analysis in low molecular weight serum peptidome biomarkers for NSCLC

ObjectsLung cancer is one of the leading causes of death from cancer in the world. Screening new serum biomarkers is important for the early detection of lung cancer. The purpose of this study was to investigate the serum peptide model between non‐small cell lung cancer (NSCLC) patients and healthy controls, as well as between paired pre‐ and postoperative NSCLC patients, and to find the low molecular weight (LMW) potential tumor markers for NSCLC.Methods56 serum samples from NSCLC patients, 56 controls, and 20 matched pre‐ and postoperative patients were analyzed using magnetic‐bead (MB)‐based purification technique combined with MALDI‐TOF‐MS. To distinguish NSCLC from cancer‐free controls, three models were established. Finally, comparing the three groups of serum protein fingerprints, nano‐liquid chromatography–electrospray ionization tandem mass spectrometry was used to further identify the differential peptides.ResultsAmong the three models constructed, the GA model had the best diagnostic efficacy. Five differential peaks were screened by combining the case group, healthy controls, and postoperative group analysis, which were up‐regulated in the case group and showed a tendency to return to healthy control values after surgery. The protein matching the mass spectrometry peak m/z 2953.73 was identified as fibrinogen α chain.ConclusionThis study shows that the application of MALDI‐TOF‐MS is a promising approach for the identification of potential serum biomarkers for NSCLC, which is potentially valuable for establishing a new diagnostic method for lung cancer. In addition, we found that fibrinogen α chain may be an auxiliary diagnostic indicator for NSCLC.     

Effect of miR‐630 expression on esophageal cancer cell invasion and migration

BackgroundEsophageal cancer (EC) is a common malignancy of the digestive tract, with high incidence. The objective of this study was to investigate the effect of miR‐630 expression on esophageal cancer (EC) cell invasion and migration.MethodsThe study group comprised 58 EC patients admitted to our hospital from April 2014 to 2016, and the control group comprised 60 healthy people visiting the hospital during the same period. miR‐630 levels in the peripheral blood of the two groups were compared, and the diagnostic value of miR‐630 for EC was analyzed. EC cell lines were used to evaluate the influence of miR‐630 expression on EC cell invasion and migration.ResultsmiR‐630 expression was low in EC (p < 0.050). A receiver operating characteristic curve analysis showed that miR‐630 expression had a good diagnostic value for EC (p < 0.050) and was associated with disease course, pathological stage, differentiation degree, tumor metastasis, and patient prognosis and survival (p < 0.05). The ROC curve analysis showed that when cutoff value was 5.38, the diagnostic sensitivity and specificity of miR‐630 for EC were 73.33% and 76.67%, respectively; area under the ROC curve was 0.778 (95%CI 0.695–0.861). Transfection of miR‐630 into EC cells indicated that miR‐630 overexpression can reduce EC cell invasion and migration (p < 0.05). miR‐630 expression is low in EC and has good diagnostic value for EC.ConclusionmiR‐630 overexpression can reduce EC cell invasion and migration, showing a possible key role of miR‐630 in EC diagnosis and treatment in the future.     

Diagnostic value of HSP90α and related markers in lung cancer

PurposeTo investigate the expression of heat shock protein 90α (HSP90α) in patients with lung cancer (LC) and the clinical value of HSP90α and other related markers in the diagnosis of LC.MethodsOf 335 patients enrolled in the study cohort, 175 were screened for LC and 160 were healthy (HC). The plasma levels of HSP90α and related markers (CEA, NSE, CYFRA21‐1 and ProGRP) were detected in all individuals in the cohort by enzyme‐linked immunosorbent assay (ELISA). Groups were divided according to gender (male/female), age (≤60 years/>60 years), types of LC (small‐cell carcinoma, squamous carcinoma and adenocarcinoma), staging (I, II, III and IV) and metastasis (metastasis and non‐metastasis) separately. Wilcoxon Mann–Whitney test and Kruskal–Wallis test were used to compare statistical differences between two groups/among the multiple groups for each factor of HSP90α. The r‐value and Kappa were used to compare HSP90α with related markers, and the receiver operating curve (ROC) was used to evaluate the efficacy of plasma HSP90α in predicting LC.ResultsNo statistical difference was found in the plasma level of HSP90α among different age and gender groups (p > 0.05). In the group divided by LC type, staging and metastasis status, there were statistical differences among different groups in HSP90α level (p < 0.05). The levels of HSP90α, CEA, NSE, CYFRA21‐1 and ProGRP in LC groups were significantly higher than HC (p < 0.001). R values of HSP90α correlated with other related markers in the diagnosis of LC (p < 0.05). Although HSP90α and other related markers did not fit the satisfactory conformance, in terms of the positive rate of diagnosis, it was statistically differences in the diagnostic positive rate between HSP90α and each marker (p < 0.01). ROC analysis showed that a plasma HSP90α cut‐off point of 50.02 ng/ml had an optimal predictive value for LC.ConclusionsHSP90α has significant clinical value in early screening and diagnosis of LC. The combined application of HSP90α and related markers can improve the positive rate of early diagnosis of LC effectively.     

Increased serum exosomal long non‐coding RNA SNHG15 expression predicts poor prognosis in non‐small cell lung cancer

BackgroundCirculating long non‐coding RNAs (lncRNAs) are emerging as promising biomarkers for non‐small cell lung cancer (NSCLC). This study aimed to detect serum exosomal lncRNA SNHG15 expression in NSCLC and evaluate its potential clinical value.MethodsA total of 238 serum samples were collected from 118 patients with NSCLC, 40 patients with benign pulmonary lesions and 80 healthy volunteers. The expression levels of serum exosomal lncRNA SNHG15 were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). Then, the relationship between serum exosomal lncRNA SNHG15 expression and clinical parameters was analyzed.ResultsThe serum exosomal lncRNA SNHG15 expression was markedly higher in NSCLC patients compared to patients with benign pulmonary lesions and normal controls. As expected, serum exosomal lncRNA SNHG15 was greatly decreased after surgery. High serum exosomal lncRNA SNHG15 expression was closely associated with poor differentiation (p=0.035), positive lymph node metastasis (p=0.009) and advanced TNM stage (p<0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that serum exosomal lncRNA SNHG15 well differentiated all stage NSCLC, stage I/II NSCLC patients or stage III/IV NSCLC patients from controls, and the combination of serum exosomal lncRNA SNHG15 and CEA showed an elevated AUC for distinguishing NSCLC from healthy individuals. In univariate and multivariate analyses, serum exosomal lncRNA SNHG15 was confirmed as an independent prognostic predictor for overall survival.ConclusionIn conclusion, our findings suggest that serum exosomal lncRNA SNHG15 might be a potential biomarker for early diagnosis and prognosis prediction of NSCLC.     

Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR‐21‐5p/TXNIP axis

BackgroundLung cancer is one of the most common malignancies globally and a significant component of cancer‐related deaths. The lack of early diagnosis accounts for detecting approximately 75% of cancer patients at an intermediate to an advanced stage, with a low 5‐year survival rate. Therefore, a more comprehensive understanding of the molecular mechanisms of lung cancer development is necessary to find reliable and effective therapeutic and diagnostic biomarkers.Methodscirc_SAR1A, miR‐21‐5p, and TXNIP in lung cancer tissues, animal xenografts, and cell lines were validated by qRT‐PCR and western blotting analyses. RNase R digestion and nuclear/cytoplasm fractionation experiments were utilized to determine the stability and localization of circ_SAR1A in lung cancer cells. The binding between miR‐21‐5p and circ_SAR1A or TXNIP was confirmed by luciferase reporter, RNA pull‐down, Spearman''s correlation, and rescue assays. CCK‐8, colony formation, flow cytometry, Transwell, and western blotting were utilized to illustrate the malignant behavior of lung cancer cells.Resultscirc_SAR1A and TXNIP were down‐regulated while miR‐21‐5p was up‐regulated in lung cancer samples and cells. circ_SAR1A was located predominantly in the cytoplasm; it inhibited lung cancer growth in vitro and in vivo by sponging to miR‐21‐5p. miR‐21‐5p silencing suppressed lung cancer malignancy by targeting TXNIP.Conclusionscirc_SAR1A is a critical negative regulator of lung carcinogenesis. circ_SAR1A/miR‐21‐5p/TXNIP attenuation inhibited lung cancer progression, presenting an ideal diagnostic and a potential therapeutic target.     

Elevated serum eotaxin and IP‐10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma

Background and AimsEsophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC.MethodsIn the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL‐2, IL‐5, IP‐10, IL‐8, eotaxin, TNF‐α, HGF, and MIP‐1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera.ResultsIn the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP‐10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early‐stage (0‐IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21‐1 (in use clinically) with eotaxin or IP‐10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21‐1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001).ConclusionsThe data suggest that serum eotaxin and IP‐10 might be potential biomarkers for the detection of ESCC.     

A combined biomarker panel shows improved sensitivity and specificity for detection of ovarian cancer

BackgroundCombined biomarkers can improve the sensitivity and specificity of ovarian cancer (OC) diagnosis and effectively predict patient prognosis. This study explored the diagnostic and prognostic values of serum CCL18 and CXCL1 antigens combined with C1D, FXR1, ZNF573, and TM4SF1 autoantibodies in OC.MethodsCCL18 and CXCL1 monoclonal antibodies and C1D, FXR1, ZNF573, and TM4SF1 antigens were coated with microspheres. Logistic regression was used to construct a serum antigen‐antibody combined detection model; receiver‐operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of the model; and the Kaplan‐Meier method and Cox regression models were used for survival analysis to evaluate the prognosis of OC. Data from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) projects and online survival analysis tools were used to evaluate prognostic genes for OC. The CIBERSORT immune score was used to explore the factors influencing prognosis and their relationship with tumor‐infiltrating immune cells.ResultsThe levels of each index in the blood samples of patients with OC were higher than those of the other groups. The combined detection model has higher specificity and sensitivity in the diagnosis of OC, and its diagnostic efficiency is better than that of CA125 alone and diagnosing other malignant tumors. CCL18 and TM4SF1 may be factors affecting the prognosis of OC, and CCL18 may be related to immune‐infiltrating cells.ConclusionsThe serum antigen‐antibody combined detection model established in this study has high sensitivity and specificity for the diagnosis of OC.     

Clinical value of serum miR‐92 and miR‐122 expression level combined with pulmonary ultrasound score in the prognosis of neonatal acute respiratory distress syndrome

PurposeTo explore the value of the expression of serum miR‐92 and miR‐122 combined with lung ultrasound score (LUS) in the prognosis of neonatal acute respiratory distress syndrome (ARDS).Patients and methodsThis study involved 148 neonatal ARDS cases from January 2018 to October 2021, of which 77 children were discharged from hospital and 31 died. The children with ARDS were classified according to disease severity based on X‐ray examination as mild (n = 69 cases) and severe (n = 39 cases). The expression of serum miR‐92 and miR‐122 was detected by real‐time fluorescence quantitative PCR and the LUS score was recorded. The data were subjected to ROC curve analysis and Pearson correlation analysis.ResultsThe expression of serum miR‐92, miR‐122, and LUS score in the patients that died were significantly higher than in those who survived (p < 0.05). These indicators were also significantly higher in the severe disease group compared to the mild disease group (p < 0.05). ROC curve showed that serum miR‐92 and miR‐122 combined with the LUS score had the largest area under the curve (0.920, 95% CI: 0.860–0.977) for predicting death, with a sensitivity and specificity of 92.0% and 87.0%, respectively. Pearson correlation analysis showed that the expression levels of serum miR‐92 and miR‐122 were positively correlated with the LUS score (all p < 0.01).ConclusionsThe increased expression of serum miR‐92 and miR‐122 is related to the severity and prognosis of children with ARDS, combined with the LUS score are of value to predict the prognosis of children with ARDS.