Serum exosomal lncRNA SNHG7 is increased in NSCLC and predicts unfavorable prognosis

Abstract BackgroundExosomal long non-coding RNAs (lncRNAs) are proposed as promising non-invasive biomarkers for clinical applications.AimsIn this study, we aimed to explore the potential of serum exosomal lncRNA SNHG7 for the diagnosis and prognosis prediction of non-small-cell lung cancer (NSCLC).MethodsA total of 128 patients with NSCLC and 80 healthy volunteers were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression level of serum exosomal lncRNA SNHG7 in all participants. Receiver operating characteristic (ROC) analysis was used to analyze the diagnostic value of serum exosomal lncRNA SNHG7 and CEA for NSCLC. The relationship between serum exosomal lncRNA SNHG7 expression and clinical characteristics of NSCLC was also assessed.ResultsSerum exosomal lncRNA SNHG7 levels were significantly upregulated in NSCLC patients compared to controls. In addition, serum exosomal lncRNA SNHG7 yield a ROC area under the curve (AUC) value of 0.856 with 77.34% sensitivity and 83.75% specificity for identifying NSCLC patients from normal controls. Combining serum exosomal lncRNA SNHG7 and CEA improved the diagnostic accuracy of NSCLC, with an AUC of 0.932 with 88.28% sensitivity and 86.25% specificity. Moreover, serum exosomal SNHG7 levels were significantly downregulated in post-operative blood samples whereas markedly higher in patients who experienced a relapse. Significant associations of elevated serum exosomal lncRNA SNHG7 expression with TNM stage, lymphatic invasion and lymph node metastasis were observed. High serum exosomal SNHG7 expression was associated with poorer survival and served as an independent prognostic factor for NSCLC.ConclusionsIn conclusion, our data demonstrates that serum exosomal SNHG7 expression might be a potential valuable biomarker for NSCLC detection and prognosis prediction.

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Diagnostic Value of Vaginal Microecology, Serum miR-18a, and PD-L1 for Identifying HPV-Positive Cervical Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821995281 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199528

Author(s):

Yumei Zhang ◽

Sujuan Qiu ◽

Yueli Guo ◽

Jiaqin Zhang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Cervical Cancer ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

High Serum ◽

Control Group ◽

Observation Group ◽

Positive Group ◽

Microbial Dysbiosis ◽

Programmed Death

Objective: We aimed to investigate the diagnostic value of the vaginal microecology, serum miR-18a, and programmed death ligand-1 (PD-L1) for human papillomavirus (HPV)-positive cervical cancer. Methods: Eighty-four patients with HPV-positive cervical cancer were assigned to the observation group, 107 HPV-positive patients without cervical cancer were assigned to the positive group, and 191 healthy women were assigned to the control group. Vaginal microecology and serum levels of miR-18a and PD-L1 on the surface of CD4+ and CD8+ T cells were compared among the 3 groups. The observation group was further divided into subgroups according to patients’ characteristics for comparison. The diagnostic value of miR-18a and PD-L1 for HPV-positive cervical cancer was investigated. Results: Women in the control group had better vaginal microecology and lower levels of miR-18a and PD-L1 than those in the observation and the positive groups (all P < 0.05). Compared with the positive group, the observation group had similar vaginal microecology (all P > 0.05) but higher levels of miR-18a and PD-L1 (all P < 0.05). Moreover, the patients at stage III had higher levels of miR-18a and PD-L1 than those at stage I and II (all P < 0.05). The values of area under the curve for miR-18a and PD-L1 in the diagnosis of HPV-positive cervical cancer were over 0.8 (all P < 0.001). Conclusion: Patients with HPV-positive cervical cancer have vaginal microbial dysbiosis and high serum levels of miR-18a and PD-L1. miR-18a and PD-L1 have diagnostic value for identifying HPV-positive cervical cancer.

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Role of ssDNA as a Noninvasive Indicator for the Diagnosis and Prognosis of Hepatocellular Carcinoma: An Exploratory Study

Disease Markers ◽

10.1155/2021/9958909 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Qi Zhao ◽

Yiqiu Xu ◽

Dandan Yuan ◽

Junjun Yang ◽

Ying Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Exploratory Study ◽

Magnetic Beads ◽

Area Under The Curve ◽

Radical Resection ◽

Diagnostic Value ◽

Healthy Individuals ◽

Diagnosis And Prognosis ◽

Imaging Results

Background and Aim. This exploratory study explored single-stranded DNA (ssDNA) for hepatocellular carcinoma (HCC) diagnosis and prognosis. Methods. This prospective study enrolled 102 patients with newly diagnosed HCC, 21 with cirrhosis, 20 with chronic hepatitis, 284 with nonliver diseases, and 45 healthy individuals at the Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University (May-October 2018). ssDNA was extracted using magnetic beads and quantified using the Qubit ssDNA assay. ssDNA levels were compared among the disease groups and in HCC vs. non-HCC. Receiver operating characteristic (ROC) curves were used to determine the diagnostic value of ssDNA. In patients with resectable HCC, ssDNA and α-fetoprotein (AFP) levels were measured during follow-up and compared with HCC recurrence detected by imaging. Results. The median ssDNA levels were higher in HCC than in healthy individuals, cirrhosis, and chronic hepatitis (median, 23.20 vs. 9.36, 9.64, and 9.76 ng/μL, respectively, P < 0.001 ). ssDNA levels in HCC were higher than those in cirrhosis and chronic hepatitis (both P < 0.001 ); there were no differences in ssDNA levels between healthy controls and patients with cirrhosis ( P = 0.15 ) or chronic liver disease ( P = 0.39 ). The area under the curve of ssDNA for HCC diagnosis was 0.909 (95% CI: 0.879-0.933). The ssDNA levels decreased by 3.19-fold ( P < 0.001 ) after HCC radical resection. In six patients, the ssDNA levels increased about 3-6 months before a recurrence was detected by AFP and imaging. Conclusions. ssDNA might be a noninvasive indicator for HCC diagnosis and prognosis. ssDNA could eventually be complementary to AFP levels and imaging, but confirmatory studies are necessary.

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A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm

Life ◽

10.3390/life11101080 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1080

Author(s):

Radu-Stefan Miftode ◽

Daniela Constantinescu ◽

Corina Maria Cianga ◽

Antoniu Octavian Petris ◽

Amalia-Stefana Timpau ◽

...

Keyword(s):

Heart Failure ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

Control Group ◽

Diagnosis And Prognosis ◽

Test Kit ◽

Positive Correlations ◽

Lactate Levels ◽

A Prospective Study

Background: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians’ interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. Methods: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. Results: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). Conclusions: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.

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The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms

BMC Cancer ◽

10.1186/s12885-021-08986-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiaoling Zhuge ◽

Hao Zhou ◽

Liming Chen ◽

Hui Chen ◽

Xiao Chen ◽

...

Keyword(s):

Serum Ferritin ◽

Invasive Carcinoma ◽

Elevated Serum ◽

Area Under The Curve ◽

Carbohydrate Antigen ◽

High Serum ◽

Tumor Biomarker ◽

Intraductal Papillary Mucinous Neoplasms ◽

Lesion Location ◽

Mucinous Neoplasms

Abstract Background Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). Methods A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. Results Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p < 0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01–1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78–17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19–9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19–9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). Conclusions Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.

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Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0508 ◽

2019 ◽

Vol 58 (1) ◽

pp. 40-49

Author(s):

Lieve Van Hoovels ◽

Bert Vander Cruyssen ◽

Laura Bogaert ◽

Stefanie Van den Bremt ◽

Xavier Bossuyt

Keyword(s):

Rheumatoid Arthritis ◽

Infectious Disease ◽

Disease Activity ◽

Clinical Performance ◽

Area Under The Curve ◽

Diagnostic Value ◽

Healthy Controls ◽

Reactive Protein ◽

Diagnosis And Prognosis ◽

Edta Plasma

Abstract Background There is a need for additional biomarkers to assist in the diagnosis and prognosis of rheumatoid arthritis (RA). The aim of our study was to evaluate the (pre-analytical, analytical and clinical) performance of serum calprotectin as a marker of inflammation in RA. Methods The study population included 463 rheumatologic patients (including 111 RA patients and 352 controls) who for the first time consulted a rheumatologist, 20 healthy controls and 27 patients with an infectious disease. Calprotectin was measured (using four different assays) in serum or in serum and EDTA plasma (healthy controls and infectious disease group). For rheumatologic patients, results for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were available. Results Results for blood calprotectin were assay- and matrix-dependent, with higher values found in serum than in plasma. Serum calprotectin was higher in RA patients than in rheumatologic diseased controls and in healthy controls. Serum calprotectin was lower in RA patients than in patients with an infectious disease. Serum calprotectin was associated with disease activity (DAS score). The area under the curve (AUC) to discriminate RA from controls was 0.756 for CRP, 0.714 for ESR and 0.726–0.783 for calprotectin. Conclusions Our data document that calprotectin measurement is assay- and matrix-dependent. Serum calprotectin is associated with disease activity. Additional (prospective) studies are warranted to further evaluate the prognostic and diagnostic value of blood calprotectin measurements.

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Serum Exosomal lncRNA DLX6-AS1 Is a Promising Biomarker for Prognosis Prediction of Cervical Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821990060 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199006

Author(s):

Xian-zhen Ding ◽

Shi-qiang Zhang ◽

Xiao-lan Deng ◽

Jin-hu Qiang

Keyword(s):

Cervical Cancer ◽

Intraepithelial Neoplasia ◽

Figo Stage ◽

Prognostic Indicator ◽

High Serum ◽

Clinical Role ◽

Prognosis Prediction ◽

Diagnosis And Prognosis ◽

Cancer Types

Objective: Deregulation of long noncoding RNAs (lncRNAs) is involved in the initiation and progression of cancer. LncRNA DLX6-AS1 is regarded as an oncogene in many cancer types. However, the clinical role of serum exosomal lncRNA DLX6-AS1 in cervical cancer (CC) is poorly known. This study aimed to analyze the diagnostic and prognostic value of serum exosomal lncRNA DLX6-AS1 in CC. Methods: A total of 114 patients with CC, 60 patients with CIN (cervical intraepithelial neoplasia), and 110 healthy women were enrolled in this study. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the serum exosomal lncRNA DLX6-AS1 levels in all participants. Results: Serum exosomal lncRNA DLX6-AS1 level was significantly elevated in CC patients compared with CIN patients and normal controls. In addition, high serum exosomal lncRNA DLX6-AS1 expression was positively associated with lymph node metastasis, differentiation, FIGO stage, and shortened survival. Patients with high serum exosomal lncRNA DLX6-AS1 expression were more prone to have a relapse. Furthermore, univariate and multivariate analyses suggested that serum exosomal lncRNA DLX6-AS1 was a potential prognostic indicator for overall survival of CC patients. Conclusions: These findings demonstrated that serum lncRNA DLX6-AS1 might serve as a promising marker for the diagnosis and prognosis prediction of CC.

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

Technology in Cancer Research & Treatment ◽

10.1177/1533033820970667 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097066

Author(s):

Huajuan Qiu ◽

Duoxian Liang ◽

Limin Liu ◽

Qun Xiang ◽

Zhijun Yi ◽

...

Keyword(s):

Cervical Cancer ◽

Healthy Subjects ◽

Early Stage ◽

High Serum ◽

The Cancer Genome Atlas ◽

Molecular Signature ◽

Circulating Mirna ◽

Prognosis Prediction ◽

Diagnosis And Prognosis ◽

Low Serum

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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Presepsin: A potential biomarker of PJI? A comparative analysis with known and new infection biomarkers

International Journal of Immunopathology and Pharmacology ◽

10.1177/0394632017749356 ◽

2017 ◽

Vol 31 ◽

pp. 039463201774935 ◽

Cited By ~ 11

Author(s):

Monica Gioia Marazzi ◽

Filippo Randelli ◽

Marco Brioschi ◽

Lorenzo Drago ◽

Carlo Luca Romanò ◽

...

Keyword(s):

Inflammatory Responses ◽

Joint Infection ◽

Area Under The Curve ◽

Roc Curves ◽

Diagnostic Value ◽

Reactive Protein ◽

Diagnosis And Prognosis ◽

Diagnostic Potential ◽

Potential Biomarker ◽

No Gold Standard

There is still no “gold standard” for the diagnosis and prognosis of post-operative periprosthetic joint infection (PJI). Among serum biomarkers, an emerging molecule is presepsin, the soluble fraction of CD14, recently described in other settings as a powerful diagnostic tool to detect sepsis at different degrees of severity. The aim of this study was to investigate the diagnostic and prognostic value of presepsin in PJI. A total of 30 patients with PJI and 30 patients without PJI were enrolled. Presepsin, C-reactive protein (CRP), serum interleukin (IL)-6, triggering receptor expressed on myeloid cells 1 (TREM-1), CCL2, matrix metalloproteinase 9 (MMP-9), CD163, osteopontin (OPN), and toll-like receptor 2 (TLR2) were measured at different times after surgery. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Presepsin showed greater diagnostic value than CRP and IL-6; CD163, TREM-1, and MMP-9 had very low diagnostic potential. Presepsin, OPN, CCL2, suPAR, and TLR2 all decreased significantly with increasing time of recovery after surgery in PJI patients. Presepsin can be considered a useful tool for the diagnosis and clinical monitoring of PJI and can be backed by a panel of new inflammatory markers involved in monocyte-/macrophage-mediated inflammatory responses, such as OPN, CCL2, TLR2, and suPAR.

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Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study

SAGE Open Medicine ◽

10.1177/2050312118773953 ◽

2018 ◽

Vol 6 ◽

pp. 205031211877395 ◽

Cited By ~ 16

Author(s):

Md Rabiul Islam ◽

Md Reazul Islam ◽

Imtiaz Ahmed ◽

Abdullah Al Moktadir ◽

Zabun Nahar ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Elevated Serum ◽

Area Under The Curve ◽

Serum Levels ◽

Significant Negative Correlation ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Characteristic Analysis ◽

Major Depressive

Objectives: Major depressive disorder is diagnosed on the basis of patient’s self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. Methods: We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. Results: We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients ( r =−0.170, p = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. Conclusion: The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder.

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Evaluation of salivary biomarkers for the diagnosis of periodontitis

BMC Oral Health ◽

10.1186/s12903-021-01600-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yong Zhang ◽

Ni Kang ◽

Fei Xue ◽

Jing Qiao ◽

Jinyu Duan ◽

...

Keyword(s):

Periodontal Disease ◽

Healthy Subjects ◽

Type I Collagen ◽

Area Under The Curve ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Cross Sectional ◽

Diagnostic Potential ◽

Auc Value

Abstract Background Salivary interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Porphyromonas gingivalis (Pg) are related to periodontitis. This study aimed to investigate the diagnostic potential of these biomarkers and to build a prediction panel for diagnosing periodontal disease. Methods A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (n = 25), gingivitis (n = 24), and periodontitis (n = 31) groups based on their periodontal exam results. A full mouth periodontal examination was performed and unstimulated saliva was collected. Salivary IL-1β, MMP-8, ICTP, and Pg were assessed using enzyme-linked immunosorbent assay (ELISA) and quantitative real time PCR (qPCR). Their potentials for diagnosing periodontal disease were analyzed and combined prediction panels of periodontal disease were evaluated. Results As a single marker, IL-1β showed the best diagnostic value of the four markers evaluated and exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects, an AUC value of 0.80 with 83% sensitivity and 76% specificity for discriminating gingivitis subjects from healthy subjects and an AUC value of 0.66 with 68% sensitivity and 64% specificity for differentiating periodontitis subjects from gingivitis subjects. The combination of IL-1β, ICTP, and Pg exhibited the highest efficacy for discriminating periodontitis subjects from healthy subjects (AUC = 0.94) and gingivitis subjects (AUC = 0.77). The combination of IL-1β and MMP-8 exhibited the best ability to discriminate gingivitis from healthy subjects (AUC = 0.84). Conclusions Salivary IL-1β, MMP-8, ICTP, and Pg showed significant effectiveness for diagnosing periodontal disease. The combination of IL-1β, ICTP, and Pg can be used to discriminate periodontitis subjects from healthy subjects and gingivitis subjects, and the combination of IL-1β and MMP-8 can be used to discriminate gingivitis subjects from healthy subjects.

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