Circulating tumor cells (CTCs) are cancer cells shed from either the primary tumor or its metastases that circulate in the peripheral blood. The CTCs are regarded as the source of tumor recurrence and metastasis and speculated as the indicators of residual tumors, thereby indicating a poor prognosis. Although CTCs play a vital role in tumor metastasis and recurrence, little is known about the underlying survival mechanisms in the blood circulation. The accumulating evidence has revealed that CTCs might survive in the peripheral blood by overcoming the mechanical damage due to shear stress, resistance to anoikis, evasion of immune destruction, and resistance to chemotherapy. The present review addresses the putative survival mechanisms underlying the formation and migration of CTCs according to their biological characteristics and blood microenvironment. In addition, the relationship between CTCs and microenvironment is illustrated, and the influencing factors related to the interactions of CTCs with various components in the peripheral blood are reviewed with respect to the platelets, immune cells, cytokines, and circulating tumor microemboli (CTM). Furthermore, the recent advances in the new treatment strategies targeting the survival mechanisms of CTCs are also discussed.

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1⁺ macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1⁺ macrophages promote integrin αvβ5/adenosine 5'-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1⁺ macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1⁺ macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvβ5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1⁺ macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy.

Postoperative recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). This study was conducted to evaluate the impact of postoperative complications on HCC recurrence after curative resection. The postoperative outcomes of 274 HCC patients who underwent curative resection were analysed retrospectively. Of the 247 HCC patients, 103 (37.6 %) patients developed postoperative complications. The occurrence of postoperative complications was found to be associated with a significantly higher tumor recurrence (76.2 % vs. 56.6 %, P = 0.002) and a lower 5-year overall survival rate (27.7 % vs. 42.1 %; P = 0.037) as compared with those without complications. Regarding the recurrence pattern, early recurrence (≤2 years) was more frequently seen in patients with complications than that in patients without complications (54.5 % vs.38.6 %; P = 0.011). Multivariate analysis indicated that postoperative complications occurrence was an independent risk factor for early recurrence (odds ratio [OR] 2.223; 95 % confidence intervals [95 % CI] 1.161–4.258, P = 0.016) and poor overall survival (OR 1.413; 95 % CI, 1.012–1.971, P = 0.042). The results of the present study indicate that the occurrence of postoperative complications is a predictive factor for HCC recurrence after curative hepatectomy, especially for early recurrence.

Background: Long-term outcomes of partial liver resection of hepatocellular carcinoma (HCC) remain satisfactory due to high incidences of recurrence. This study was intended to see whether preoperative transcatheter arterial chemoembolization (TACE) reduces postoperative tumor recurrences and prolongs survival of patients with resectable HCC. Methods: A computerized literature search was performed to identify relevant articles. The quality of nonrandomized comparative studies (NRCTs) was assessed using the methodological index for nonrandomized studies (MINORS). Data synthesis was performed using Review Manager 5.0 software. Results: Twenty-one studies (4 randomized controlled trials and 17 NRCTs) with a total of 3,210 participants were suitable for analysis. There was no significant difference in disease-free and overall survival at 5-year (32.1% vs. 30.0% and 40.2% vs. 45.2%), and intra- and extra-hepatic recurrence (51.2% vs.53.6% and 12.9% vs.10.3%) between patients with and without preoperative TACE. Postoperative morbidity (28.9% vs. 26.8%) and in-hospital mortality (4.1% vs. 3.1%) were also similar between the two groups. Conclusions: Preoperative TACE does not seem to improve prognosis and therefore it is prudent to recommend it as a preoperative routine procedure for resectable HCC.

Background. Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, which was highly correlated with metabolic dysfunction. Nevertheless, the association between nuclear mitochondrial‐related transcriptome and HCC remained unclear. Materials and Methods. A total of 147 nuclear mitochondrial‐related genes (NMRGs) were downloaded from the MITOMAP: A Human Mitochondrial Genome Database. The training dataset was downloaded from The Cancer Genome Atlas (TCGA), while validation datasets were retrieved from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The univariate and multivariate, and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied to construct a NMRG signature, and the value of area under receiver operating characteristic curve (AUC) was utilized to assess the signature and nomogram. Then, data from the Genomics of Drug Sensitivity in Cancer (GDSC) were used for the evaluation of chemotherapy response in HCC. Results. Functional enrichment of differentially expressed genes (DEGs) between HCC and paired normal tissue samples demonstrated that mitochondrial dysfunction was significantly associated with HCC development. Survival analysis showed a total of 35 NMRGs were significantly correlated with overall survival (OS) of HCC, and the LASSO Cox regression analysis further identified a 25‐NMRG signature and corresponding prognosis score based on their transcriptional profiling. HCC patients were divided into high‐ and low‐risk groups according to the median prognosis score, and high‐risk patients had significantly worse OS (median OS: 27.50 vs. 83.18 months, P < 0.0001). The AUC values for OS at 1, 3, and 5 years were 0.79, 0.77, and 0.77, respectively. The prognostic capacity of NMRG signature was verified in the GSE14520 dataset and ICGC‐HCC cohort. Besides, the NMRG signature outperformed each NMRG and clinical features in prognosis prediction and could also differentiate whether patients presented with vascular invasions (VIs) or not. Subsequently, a prognostic nomogram (C‐index: 0.753, 95% CI: 0.703~0.804) by the integration of age, tumor metastasis, and NMRG prognosis score was constructed with the AUC values for OS at 1, 3, and 5 years were 0.82, 0.81, and 0.82, respectively. Notably, significant enrichment of regulatory and follicular helper T cells in high‐risk group indicated the potential treatment of immune checkpoint inhibitors for these patients. Interestingly, the NMRG signature could also identify the potential responders of sorafenib or transcatheter arterial chemoembolization (TACE) treatment. Additionally, HCC patients in high‐risk group appeared to be more sensitive to cisplatin, vorinostat, and methotrexate, reversely, patients in low‐risk group had significantly higher sensitivity to paclitaxel and bleomycin instead. Conclusions. In summary, the development of NMRG signature provided a more comprehensive understanding of mitochondrial dysfunction in HCC, helped predict prognosis and tumor microenvironment, and provided potential targeted therapies for HCC patients with different NMRG prognosis scores.

Little is known about the prognostic impact of cirrhosis on long-term survival of patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC) after hepatic resection. The aim of this study was to elucidate the long-term outcome of hepatectomy in cHCC-CC patients with cirrhosis. A total of 144 patients who underwent curative hepatectomy for cHCC-CC were divided into two groups: cirrhotic group (n = 91) and noncirrhotic group (n = 53). Long-term postoperative outcomes were compared between the two groups. Patients with cirrhosis had worse preoperative liver function, higher frequency of HBV infection, and smaller tumor size in comparison to those without cirrhosis. The 5-year overall survival rate in cirrhotic group was significantly lower than that in non-cirrhotic group (34.5% versus 54.1%, P = 0.032). The cancer recurrence-related death rate was similar between the two groups (46.2% versus 39.6%, P = 0.446), while the hepatic insufficiency-related death rate was higher in cirrhotic group (12.1% versus 1.9%, P = 0.033). Multivariate analysis indicated that cirrhosis was an independent prognostic factor of poor overall survival (hazard ratio 2.072, 95% confidence interval 1.041–4.123; P = 0.038). The presence of cirrhosis is significantly associated with poor prognosis in cHCC-CC patietns after surgical resection, possibly due to decreased liver function.