Differential expression and diagnostic significance of P53, MutS homologs 2, tropomyosin-4 in alpha-fetoprotein-negative hepatocellular carcinoma.

BACKGROUND: Current study aimed to explore the value of P53, MutS homologs 2 (MSH2), and tropomyosin-4 (Tm-4) combined with inflammatory factors, life-history traits in the differential diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma (AFP-Negative HCC). METHODS: A testing cohort including 280 AFP-Negative HCC patients and 300 controls was included. Three external validation cohorts from 3 centers were used to assess the novel logistic regression model including 400 AFP-Negative HCC patients and 400 controls. RESULTS: Compared with the control group, the levels of P53, MSH2, and Tm-4 protein in si-P53 group, si-MSH2 group, and si-Tm-4 group were significantly reduced (P < .05). The P53, MSH2, Tm-4, neutrophil to lymphocyte ratio (NLR), monocytes to lymphocyte ratio (MLR), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) levels, and the smoking, drinking, and occupational exposure to chemicals rates in patients were significantly higher than those in controls (P < .05). ROC analyses showed that the area under curve (AUC) of NLR, MLR, hs-CRP, TNF-α, IL-6, P53, MSH2, Tm-4, drinking, smoking, and occupational exposure to chemicals were 0.798, 0.803, 0.560, 0.644, 0.808, 0.681, 0.830, 0.694, 0.582, 0.581, and 0.567, respectively. A novel logistic regression model was built and has a high value in identifying AFP-Negative HCC with AUC of 0.917, sensitivity of 85.2%, and specificity of 88.3%. In the validation cohorts, this model also showed good diagnostic efficiency (AUC = 0.898 with Dazu Branch cohort, AUC = 0.924 with Jinshan Branch cohort, and AUC = 0.907 with Liangping Branch cohort). CONCLUSION: Current model has potential significance for the noninvasive diagnosis of AFP-Negative HCC.