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

Abstract 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.