Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase–polymerase-chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor κB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa.

Purpose: More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) –related HCC. Patients and Methods: Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively. Conclusion: We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.

Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Purpose: To investigate prognostic values of the intratumoral and peritumoral expression of macrophage colony-stimulating factors (M-CSF) in hepatocellular carcinoma (HCC) patients after curative resection. Patients and Methods: Expression of M-CSF and density of macrophages (MΦ) were assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 105 patients who had undergone hepatectomy for histologically proven HCC. Prognostic value of these and other clinicopathologic factors was evaluated. Results: Neither intratumoral M-CSF nor MΦ density was associated with overall survival (OS) or disease-free survival (DFS). High peritumoral M-CSF and MΦ density, which correlated with large tumor size, presence of intrahepatic metastasis, and high TNM stage, were independent prognostic factors for both OS (P = .001 and P < .001, respectively) and DFS (P = .001 and P = .003, respectively) and affected incidence of early recurrence. In a small HCC subset, peritumoral M-CSF was also correlated with both OS and DFS (P = .038 and P = .001, respectively). The combination of peritumoral M-CSF and MΦ had a better power to predict the patients' death and disease recurrence (P < .001 for both). Conclusion: High peritumoral M-CSF and MΦ were associated with HCC progression, disease recurrence, and poor survival after hepatectomy, highlighting the importance of peritumoral tissue in the recurrence and metastasis of HCC. M-CSF and MΦ may be targets of postoperative adjuvant therapy.