LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.

Background/Objectives: Vascular invasion, especially extramural vascular invasion (EMVI), has emerged as a prognostic parameter for rectal cancer (RC) in recent years. Prediction of recurrence and metastasis development poses a significant challenge for oncologists, who need markers for prediction of adverse outcome. The aim of this study was to examine the prognostic significance of pathohistologically detected EMVI in untreated rectal cancer and its implications in separate reporting. Methods: We examined 100 untreated RC patients who underwent curative resection from January 2016 to June 2018 with a follow-up of 5 years. Patients were divided into equal EMVI− and EMVI+ groups based on histological re-examination of H&E-stained postoperative surgical samples. Results: The presence of EMVI within the selected cohort was significantly associated with female gender, T3/T4 and N1/N2 post-operative stages, positive lymph nodes, lymph node ratio LNR2 and LNR3 groups, abundant tumor-infiltrating lymphocytes, positive lympho-vascular invasion (LVI), perineural (PNI), and circumferential resection margin (CRM) (p < 0.05 in all tests). Within EMVI+ patients, local recurrences and/or metastases and death outcomes were more frequent events (p = 0.029 and p = 0.035, respectively), while survival analyses revealed that EMVI+ patients had significantly shorter overall survival (OS, p = 0.040) and disease-free survival (DFS, p = 0.028). Concerning LVI, differences in OS between LVI+ and LVI− patients were not statistically significant (p = 0.068), while LVI+ patients had significantly shorter DFS (p = 0.024). Moreover, univariate COX regression analysis demonstrated the negative impact of EMVI on OS (HR: 2.053, 95% CI: 1.015–4.152; p = 0.045) and DFS (HR: 2.106, 95% CI: 1.066–4.870; p = 0.038), which was not the case for LVI + RC patients. Conclusions: The obtained results strongly suggest the significance of separate reporting of EMVI from lympho-vascular invasion, as it is potentially a surrogate marker for adverse prognosis and outcome.

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine system, characterized by various molecular alterations. This study evaluates the relationship between p16 promoter methylation status, BRAFV600E mutation presence, and ETS1 (E26 transformation-specific) expression, aiming to better understand their clinical significance and to enhance the risk stratification of PTC patients. Methods: p16 promoter methylation was analyzed by methylation-specific PCR (MSP), BRAFV600E by mutant allele-specific PCR amplification (MASA), ETS1 mRNA expression by quantitative PCR (qPCR), ETS1 protein expression by immunohistochemistry (IHC), and Western blot. All tested factors were further associated with the occurrence of unfavorable clinicopathological data of the patients. Results: While p16 methylation did not correlate with adverse clinical parameters or BRAFV600E mutation presence, it was significantly associated with the increased ETS1 mRNA levels. Combined p16 methylation with high ETS1 protein levels was significantly associated with advanced pT and pTNM stages. BRAFV600E-mutated PTC cases with p16 methylation showed increased mRNA and protein ETS1 expression. Conclusions: Therefore, although p16 methylation could not be used as a standalone prognostic marker, its association with elevated ETS1 levels points to its potential involvement in tumor progression and adverse clinical outcomes, particularly in BRAFV600E-mutated PTCs. Deeper insights into these interactions may enhance PTC prognosis and the selection of high-risk patients.

The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival.