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Serum miR-122 correlates with short-term mortality in sepsis patients

Critical Care201418:704

Published: 12 December 2014


No abstract


  • Acute Respiratory Distress Syndrome
  • Sequential Organ Failure Assessment
  • Procalcitonin
  • Sequential Organ Failure Assessment Score
  • Chronic Health Evaluation

Sepsis is one of the leading causes of death in the ICU. The pathogenesis of sepsis remains incompletely understood, thereby impeding the development of therapeutics, diagnostics and biomarkers to predict outcomes [1]. Our previous studies have proved that miR-122, miR-193b*, miR-483-5p and miR-574-5p were all differentially expressed between sepsis survivors and non-survivors, differentiated by 28-day mortality [2],[3]. However, whether these biomarkers related to patients with both sepsis and acute respiratory distress syndrome (ARDS) remains unclear. Here we evaluate the levels of these four microRNAs (miRNAs) along with C-reactive protein (CRP), procalcitonin (PCT), Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation (APACHE) II score to determine the ideal biomarkers for sepsis patients.

Serum samples were collected from 232 sepsis patients who were admitted to ICUs of the Chinese PLA General Hospital. All the patients met the definition of sepsis developed in 2003 [4]. Inclusion and exclusion criteria are described in Table 1. Another 24 normal individuals were also included in this study. Serum levels of miRNAs, CRP and PCT were analyzed using methods as described in detail previously [3]. This study was approved by the ethics committee of the Chinese PLA General Hospital. Appropriate informed consent was obtained from each patient and normal individual.
Table 1

Inclusion and exclusion criteria

Inclusion criteria

Exclusion criteria

1) Sepsis patients all met the definitions of the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference [4]

1) Patients who were younger than 18 years old

2) Patients who were immunosuppressed

3) Patients who did not receive adequate treatment

4) Patients who did not give their written informed consent

2) All patients received standard protocols of clinical care

The clinical data of these 232 patients are shown in Table 2. After comparison of the levels of the four miRNAs in three pairs of groups (normal individuals and sepsis patients, survivors and non-survivors, sepsis without ARDS and sepsis plus ARDS), only the cycle threshold of mir-122 was differentially expressed in all three (P < 0.01) (Figure 1). Univariable and multivariable regression analyses were then used to evaluate the association between miR-122 and 28-day mortality in different ICUs. After adjustment using clinical data and additional parameters (SOFA score, APACHE II score and ARDS), the odds ratio of miR-122 association with 28-day mortality was around 0.376 to 0.868 (P < 0.05) in the different ICUs. The area under the curve for the predictive value of miR-122 was around 0.706 to 0.770 (P < 0.01) with high sensitivity and specificity (Table 3). As a result, only miR-122 can be used as a biomarker with regards to patients with both sepsis and ARDS. miR-122 is a liver-specific miRNA and levels of it in serum were correlated with drug-induced liver injury [5]. We reported that miR-122 correlated with coagulation disorders in sepsis patients and serum levels of miR-122 correlated with serum antithrombin III levels [6]. Our study reveals a potential novel target to develop a biomarker for sepsis prognosis and therapeutic strategies.
Table 2

Clinical characteristics of the 232 sepsis patients



Sepsis (n = 232)

Demographic parameters

Gender (male/female)



Age in years (median (range))

59 (19, 91)

Clinical parameters

ICU type



232 (100%)



79 (34.05%)



95 (40.95%)



25 (10.77%)



24 (10.34%)



15 (6.46%)



18 (1, 39)


SOFA score

7 (0, 19)


Acute kidney injury

61 (26.29%)


Mechanical ventilation

171 (73.71%)


Heat failure

121 (52.15%)


Liver failure

103 (44.39%)



60 (28.17%)a


28-day mortality




17.75 ± 3.40 cycles



17.73 ± 4.81 cycles



21.19 ± 3.64 cycles



18.99 ± 4.24 cycles


CRP (mg/dl)

8.9 (0.1, 35)


PCT (ng/ml)

4.63 (0.05,119.44)

aARDS data of 19 patients were missing. APACHE, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; CRP, C-reactive protein; PCT, procalcitonin; SOFA, Sequential Organ Failure Assessment. APACHE II score, SOFA score, CRP and PCT are all given as median (range).

*ARDS data of 19 patients were missing.

Figure 1
Figure 1

Cycle thresholds of the four microRNAs (miRNAs) in the three pairs of groups. ARDS, acute respiratory distress syndrome.

Table 3

The association between miR-122 levels and 28-day mortality in sepsis patients


All patients (n = 232)

RICU (n = 67)

SICU (n = 121)

EICU (n = 44)

Odds ratios of miR-122 (95% CI)



0.775 (0.703, 0.853)

0.776 (0.664, 0.908)

0.77 (0.662, 0.894)

0.764 (0.610, 0.956)


P < 0.001

P = 0.001

P = 0.001

P = 0.019


0.789 (0.713, 0.872)

0.777 (0.663, 0.911)

0.763 (0.655, 0.888)

0.650 (0.474, 0.891)


P < 0.001

P = 0.002

P < 0.001

P = 0.007

Adjustedb +

0.772 (0.690, 0.863)

0.781(0.665, 0.918)


0.631 (0.448, 0.890)

SOFA score

P < 0.001

P = 0.003

P = 0.003

P = 0.009

Adjustedb +

0.815 (0.734, 0.905)

0.709 (0.578, 0.870)

0.753 (0.639, 0.887)

0.622 (0.431, 0.897)


P < 0.001

P = 0.001

P = 0.001

P = 0.011

Adjustedb +

0.812 (0.724, 0.911)

0.868 (0.647, 0.967)

0.721 (0.599, 0.867)

0.376 (0.133, 0.865)


P < 0.001

P = 0.023

P = 0.001

P = 0.034

The predictive value of miR-122

AUC (95% CI)

0.732 (0.665, 0.799)

0.763 (0.65,0.877)

0.706 (0.611,0.802)

0.770 (0.574, 0.966)


< 0.001

< 0.001

< 0.001












aUnadjusted by any value. bAdjusted by age and gender. APACHE, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; AUC, are under the curve; EICU, Emergency Intensive Care Unit; RICU, Respiratory Intensive Care Unit; SICU, Surgery’s Intensive Care Unit; SOFA, Sequential Organ Failure Assessment.



Acute Physiology and Chronic Health Evaluation


Acute respiratory distress syndrome


C-reactive protein






Sequential Organ Failure Assessment



This work is supported by the general program of the National Natural Science Foundation of China (81170008), and the general program of China’s 12th Five Year Plan and its military (CWS11J094).

Authors’ Affiliations

Department of Respiratory Medicine, Chinese PLA General Hospital, Beijing, PR China
Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China
International Medical Center, The General Hospital of Chinese People’s Liberation Army, Beijing, China
Department of Respiratory Medicine, Beijing Nanyuan Hospital, Beijing, China
Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA


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© Wang et al.; licensee BioMed Central Ltd. 2014

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