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.

The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?

“…Liu et al concluded that des-gamma-carboxyprothrombin (DCP) can distinguish AFP-negative HBV-related HCC from chronic HBV infection (AUC = 0.731) or LC (AUC = 0.685) 48 . Several studies have attempted to combine multiple biomarkers [54][55][56][57][58][59][60][61] or serological examinations [62][63][64][65][66] . With the help of proteomics technology, researchers have identified some abnormally expressed proteins that were verified in various cancers [67][68][69][70] to construct a logistic regression model, which had good performance in distinguishing AFP-negative HCC 60 .…”

“…Several studies have attempted to combine multiple biomarkers [54][55][56][57][58][59][60][61] or serological examinations [62][63][64][65][66] . With the help of proteomics technology, researchers have identified some abnormally expressed proteins that were verified in various cancers [67][68][69][70] to construct a logistic regression model, which had good performance in distinguishing AFP-negative HCC 60 . A logistic regression model consisting of LHPP 71 -associated microRNAs (miR-363-5p and miR-765) and PIVKA-II exhibited a high identification value with an AUC of 0.930 57 .…”

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial‐level analysis

“…59 Therefore, although, in the current study, the ORR and sORR yielded similar results, they probably measure different phenomena and, in clinical practice, might evaluate different populations. Also, from a molecular point of view, the subgroup of AFP-negative patients has been characterized 60 ; whereas, in those who have HCC with high AFP levels, several AFP-related activities could be hypothesized, such as immunosuppression, 41 regulation of tumor necrosis factor cytotoxicity, 61 and FAS-associated death-domain protein downregulation. 62 Therefore, serum AFP levels should correlate with the molecular characteristics.…”