It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151 high showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo. Furthermore, HCC patients with vascular invasion, large tumors, multiple tumors, high tumor-node-metastasis stage, and undifferentiated tumor were prone to have higher CD151 expression. The postoperative 3-, 5-, and 7-year overall survival (OS) of patients in HCCs with CD151 high were significantly lower than those in the CD151 low group, and correspondingly cumulative recurrence rates in HCCs with CD151 high were significantly higher than those in the CD151 low group. Both CD151 and c-Met were remarkably overexpressed in HCCs, compared with adjacent nontumorous and normal liver tissues. Pearson correlation analysis showed a slight correlation between CD151 and c-Met in HCCs. Importantly, the 5-and 7-year OS rates in CD151 high /c-Met high patients were 50.5% and 37.8%, respectively, significantly lower than those of CD151 low /c-Met low patients (63.9% and 54.6%, respectively). Five-and 7-year cumulative recurrence rates in CD151 high /c-Met high patients were 53.3% and 71.9%, respectively, markedly higher than those of CD151 low / c-Met low patients (39.0% and 52.5%, respectively). Multivariate analysis revealed that CD151 and combination of CD151/c-Met were independent prognostic indicators for OS and cumulative recurrence. Conclusion: CD151 is positively associated with invasiveness of HCC, and CD151 or combination of CD151/c-Met is a novel marker in predicting the prognosis of HCC and a potential therapeutic target. (HEPATOLOGY 2009;49:491-503.)

The purpose of this study was to conduct a comprehensive study of the clinical correlation between the alpha-fetoprotein (AFP) level at diagnosis and pathological grades, progression, and survival of patients with hepatocellular carcinoma (HCC). A total of 78,743 patients in Surveillance, Epidemiology, and End Results Program (SEER)-registered HCC was analyzed. The AFP test results for patients with HCC were mainly recorded as AFP-negative and AFP-positive. Logistic regression analysis revealed that the AFP level at diagnosis was an independent risk factor of pathological grade (odds ratio [OR], 2.559; 95% confidence interval [CI], 2.075–3.157; P < 0.001), TNM-7 stage (OR, 2.794; CI, 2.407–3.242; P < 0.001), and tumor size (OR, 1.748; 95% CI, 1.574–1.941; P < 0.001). Multivariable Cox regression analyses identified AFP level as an independent predictor of survival risk of patients with HCC who did not undergo surgery (hazard ratio [HR], 1.660; 95% CI, 1.534–1.797; P < 0.001), and those who underwent surgery (HR, 1.534; 95% CI, 1.348–1.745; P < 0.001). The AFP level at diagnosis was an independent risk predictor associated with pathological grade, progression, and survival. Further, surgery may not significantly reverse the adverse effects of AFP-positive compared with AFP-negative.

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

Liver transplantation (LT) is one of the best therapeutic options for nonresectable hepatocellular carcinoma (HCC). Unfortunately, some HCC patients succumb to the disease after LT, which reduces long-and medium-term survival. To identify the proteins associated with HCC invasion and metastasis, HCC patients undergoing LT with complete follow-up data were included in this study and were categorized into recurrence and nonrecurrence groups. We extracted the total protein from the acquired homogeneous tumor cells and applied a cleavable isotope-coded affinity tag technology to quantitate relative changes in protein levels between the two groups. We identified a total of 149 proteins with two-dimensional liquid chromatography coupled with tandem mass spectrometry, including 52 differentially expressed proteins by at least two-fold. Among them, calpain small subunit 1 (Capn4), a protein with relevant interactions with many migration-invasion-related proteins, has attracted more attention. H epatocellular carcinoma (HCC) is one of the most prevalent human cancers worldwide, with 626,000 estimated new cases annually and almost as many deaths; 82% of cases (and deaths) occur in developing countries (with 55% in China). 1 HCC nearly always develops in the setting of chronic hepatitis virus infection or liver cirrhosis. 2-5 Surgical resection is usually considered the first choice for treatment; however, many HCC patients with cirrhosis cannot receive this treatment due to their limited liver function and extent of the tumor. Liver transplantation (LT), the only potentially curative therapeutic modality, allows radical extirpation of cancer and restores normal liver function. 6 There is increasing evidence that, in the long term, LT will be the best therapeutic option for cirrhosis-associated HCC. 7 Unfortunately, some HCC patients succumb to the disease as a result of metastasis and recurrence after LT. Therefore, recurrence-related studies have attracted more attention.Clinical features such as the number and size of nodules, microscopic/macroscopic vascular invasion, and