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Head & Neck Cancer

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lncOCMRL1 Promotes Metastasis in OSCC via EMT and RRM2 Suppression

KEY TAKEAWAYS

  • The study aimed to explore how lncOCMRL1 promotes OSCC metastasis and identify its mechanism.
  • The results showed that lncOCMRL1 promotes metastasis and growth in OSCC by inducing EMT.

Nan Lu and their team aimed to investigate the role of long noncoding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) metastasis. Metastasis is a major factor limiting cancer treatment efficacy, and the functions of many lncRNAs remain unclear. Exploring the mechanisms of metastasis-related lncRNAs could provide novel therapeutic strategies for OSCC.

The study analyzed lncRNA expression profiles in tumor tissues from OSCC patients with and without cervical lymph node metastasis, as well as in OSCC cell lines. They focused on lncOCMRL1, which was found to be highly expressed in metastatic tumors and cell lines. They assessed the effects of lncOCMRL1 knockdown on OSCC cell proliferation, invasion, and migration using qRT-PCR, Transwell, colony formation, and proliferation assays.

Additionally, they explored the molecular mechanism through RNA pull-down, silver staining, mass spectrometry, RIP, and WB techniques. A nano delivery system was developed to deliver siRNA targeting lncOCMRL1 for therapeutic purposes.

The results demonstrated that lncOCMRL1 was significantly overexpressed in metastatic OSCC tissues and cells. Functional studies showed that lncOCMRL1 promotes OSCC cell growth and metastasis both in vivo and in vitro.

The lncOCMRL1 induces epithelial-mesenchymal transition (EMT) by inhibiting RRM2 ubiquitination, facilitating OSCC cell invasion, migration, and proliferation. Reduction-responsive nanoparticles delivering siRNAs targeting lncOCMRL1 were effective in silencing its expression, significantly inhibiting tumor growth and metastasis in vivo.

The study concluded that lncOCMRL1 is a key regulator of metastasis in OSCC and a promising therapeutic target to prevent lymph node metastasis.

This work was supported by grants from the National Natural Science Foundation of China, the Science and Technology Program of Guangdong, the Guangzhou Science and Technology Project, the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University, and the Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology ([2013]163).

Source: https://pubmed.ncbi.nlm.nih.gov/39343925/

Lu N, Jiang Q, Xu T, et al. (2024). “LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway.” J Exp Clin Cancer Res. 2024;43(1):267. Published 2024 Sep 30. doi:10.1186/s13046-024-03190-w

HMMR and CDC25C as Prognostic Biomarkers in HNSCC

KEY TAKEAWAYS

  • The study aimed to identify prognostic biomarkers and explore the molecular mechanisms of HNSCC.
  • The results showed that HMMR and CDC25C could serve as potential prognostic markers in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) ranks among the most common cancers worldwide, but its underlying mechanisms remain poorly understood. Identifying potential biomarkers can improve diagnosis and treatment options.

Hongrui Zhang and the team aimed to identify prognostic biomarkers and clarify the molecular mechanisms involved in HNSCC.

Researchers applied weighted gene co-expression network analysis (WGCNA), followed by pathway enrichment, immune cell infiltration, survival, and methylation analyses, to identify hub genes related to HNSCC prognosis. They validated the expression of these hub genes using immunofluorescence staining.

The results demonstrated that 10,274 differentially expressed genes (DEGs) were identified. Through WGCNA, the yellow module (R2 = 0.33, P= 2e-14) was most associated with HNSCC histological grade, with the “Cell Cycle” pathway being highly enriched. They identified 10 hub genes, with 8 confirmed through survival analysis using a different dataset (GSE41613).

Additionally, 4 methylation loci in 3 hub genes (cg15122828, cg20554926 in HMMR, cg12519992 in CDC25C, and cg2655739 in KIAA0101/PCLAF) were significantly related to survival. High expression of HMMR and CDC25C mRNA and protein was observed in HNSCC patients.

The study concluded that HMMR and CDC25C are potential prognostic and therapeutic biomarkers in HNSCC.

This study was supported by Zhejiang Medical and Health Science and Technology Plan (Grant No. 2024KY603) to Hongrui Zhang.

Source: https://pubmed.ncbi.nlm.nih.gov/39323031/

Zhang H, Xu Y, Han H, et al. (2024). “Comprehensive Analysis Identifies Hyaluronan Mediated Motility Receptor and Cell Division Cycle 25C as Potential Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma.” Cancer Control. 2024;31:10732748241287904. doi:10.1177/10732748241287904

Exosome Internalization Induces Type 2-like Polarization

KEY TAKEAWAYS

  • The study aimed to investigate how tumor-related plasma-derived exosomes affect the polarization and characteristics of monocyte-derived macrophages.
  • Plasma-derived exosomes from patients with HNSCC cause a type 2-like polarization and increased CXCL4 secretion in monocyte-derived macrophages.

Exosomes play a crucial role in the progression of head and neck squamous cell carcinoma (HNSCC) by influencing angiogenesis and immune regulation. These extracellular vesicles facilitate intercellular communication by transporting proteins and nucleic acids.

Marie-Nicole Theodoraki sought to understand how tumor-related plasma-derived exosomes affect monocyte-derived macrophages’ polarization and characteristics.

Researchers isolated exosomes from the plasma of both healthy donors and patients with HNSCC. They then analyzed the morphology, size, and protein composition of these exosomes. Techniques such as transmission electron microscopy, nanoparticle tracking analysis, western blot analysis, and cytokine assays were used for this analysis.

They studied how internalizing these exosomes affected monocyte-derived macrophage differentiation and characteristics using flow cytometry and fluorescence microscopy. Lastly, they examined macrophage cytokine secretion patterns through human cytokine antibody arrays and ELISA measurements.

The study found higher levels of CTLA-4, PD-L1, and TIM-3 in the overall plasma of patients with HNSCC compared to healthy donors. Additionally, exosomes from patients with HNSCC showed elevated levels of CTLA-4, PD-L2, TIM-3, and LAG-3.

Researchers observed a significant type 2-like polarization and increased CXCL4 secretion in monocyte-derived macrophages after internalizing plasma-derived exosomes from patients with HNSCC, a phenomenon visualized through fluorescence microscopy of membrane-stained exosomes.

The study provided new insights into how exosomes contribute to pro-tumorigenic immune regulation in patients with HNSCC. These findings enhanced the understanding of the individual immunologic response in patients with head and neck cancer.

Open Access funding enabled and organized by Projekt DEAL. This study has been supported by a grant of the Walter-Schulz-Foundation to MNT and RP.

Source: https://pubmed.ncbi.nlm.nih.gov/39304856/

Theodoraki MN, Huber D, Hofmann L, et al. (2024). “Type 2-like polarization and elevated CXCL4 secretion of monocyte derived macrophages upon internalization of plasma-derived exosomes from head and neck cancer patients.” BMC Cancer. 2024;24(1):1173. Published 2024 Sep 20. doi:10.1186/s12885-024-12948-6

Boron Neutron Capture Therapy for Spinal Tumors

Boron Neutron Capture Therapy for Spinal Tumors

KEY TAKEAWAYS

  • The study aimed to evaluate the efficacy and safety of BNCT for metastatic spinal tumors.
  • The findings suggested that BNCT could be a novel therapeutic option for managing metastatic spinal tumors.

Metastatic spinal tumors pose a significant challenge in oncology, often requiring complex management strategies. While radiation therapy has advanced, improving the quality of life (QoL) and daily living for patients remains difficult. Boron neutron capture therapy (BNCT) offers a unique approach, enabling precise tumor targeting at the cellular level.

Yoshiki Fujikawa and the team aimed to evaluate the efficacy and safety of BNCT in a preclinical model of metastatic spinal tumors.

The study involved both in vitro and in vivo experiments. In vitro, A549 human lung adenocarcinoma cells were exposed to neutron and photon irradiation, with and without the boron carrier p-boronophenylalanine (BPA). Colony formation assays assessed the effects on cell survival.

In vivo, mice with metastatic spinal tumors received BPA intravenously, and boron biodistribution was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). For BNCT efficacy evaluation, mice were divided into untreated, neutron irradiation only, and BNCT groups. Survival, hindlimb function, and histopathological changes were assessed.

Results showed that neutron irradiation, particularly with BPA, effectively killed cancer cells in vitro. In vivo, BNCT significantly prolonged survival and preserved hindlimb function compared to the untreated and neutron-only groups. Notably, no adverse events or significant histopathological abnormalities were observed.

These findings highlighted the potential of BNCT as a safe and effective treatment for metastatic spinal tumors. Further research is warranted to translate these promising preclinical results into clinical practice.

This research was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP22K09270 to Toshihiro Takami) (Grants-in-Aid for Science Research [C]) and partly by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. JP23H03024 to S.K.) (Grants-in-Aid for Science Research [B]).

Source: https://pubmed.ncbi.nlm.nih.gov/39295333/

Fujikawa Y, Kawabata S, Tsujino K, et al. (2024). “AB015. Efficacy and safety of boron neutron capture therapy in managing metastatic spinal tumors: experimental findings.” Chin Clin Oncol. 2024;13(Suppl 1):AB015. doi:10.21037/cco-24-ab015

Autophagy-Related Genes in Tongue Cancer Affected by PP

KEY TAKEAWAYS

  • The study aimed to investigate the anti-tumor mechanisms of PP in TSCC using network pharmacology and in vitro experiments.
  • The findings suggested that PP may inhibit TSCC by activating autophagy, targeting MAPK3 and PSEN1.

Tongue squamous cell carcinoma (TSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), accounting for about one-third of all oral cancers. Paris polyphylla (PP) has shown potential anti-tumor effects, but its mechanisms are not well understood.

Jing Zhou and the team aimed to provide new insights into the molecular mechanisms of TSCC treatment with PP and lays the groundwork for its potential clinical use.

The study utilized transcriptomics and network pharmacology to identify autophagy-related genes associated with PP’s effects. These genes were then analyzed for their functions using KEGG and GO enrichment analyses.

In vitro studies were conducted on CAL-27 cells (a human TSCC cell line) treated with varying concentrations of PP (10, 30, and 60 μg/ml) for 24 hours. The effects on tumor cell proliferation, apoptosis, and autophagy markers (P62, LC3B, and Beclin1) were then assessed.

Molecular docking revealed stable interactions between PP and MAPK3 and PSEN1, suggesting their role in PP’s anti-tumor activity. The in vitro experiments showed that PP significantly inhibited the proliferation of CAL-27 cells and promoted apoptosis. Additionally, PP treatment altered the expression of autophagy markers P62, LC3B, and Beclin1, indicating autophagy activation.

The study provided evidence that PP inhibits TSCC cell growth by activating the autophagy pathway. MAPK3 and PSEN1 are identified as potential target molecules for PP’s anti-tumor effects. This research highlighted the potential of PP as a novel therapeutic agent for TSCC treatment, warranting further investigation in clinical settings.

Funding support was provided by Basic Research Project of Science and Technology Department of Yunnan Province (202301AY070001-288) and Training of Technological Innovation Talents in Yunnan Province (202405AD350091).

Source: https://pubmed.ncbi.nlm.nih.gov/39215239/

Zhou J, Zhang H, Ma L, et al. (2024). “Identification and validation of autophagy-related genes influenced by paris polyphylla in tongue cancer using network pharmacology.” BMC Oral Health. 2024;24(1):1022. Published 2024 Aug 30. doi:10.1186/s12903-024-04784-8

Microbial Variations in Oral Precancerous Disorders and Cancer

KEY TAKEAWAYS

  • The study aimed to investigate and compare the microbial communities present in different OPMDs.
  • Researchers found distinct bacterial species in OPMDs, suggesting these microbes may play a role in disease development.

The role of the oral microbiome in the development of oral cancer, a type of head and neck cancer, has become an area of increasing interest for researchers. While the link between the oral microbiome and oral cancer is being actively investigated, less is known about the microbial communities associated with oral potentially malignant disorders (OPMDs). Understanding these microbial communities could provide insight into the development and progression of these disorders.

Xuan Zhou and the team aimed to characterize and compare the microbial communities found in different OPMDs.

Researchers obtained oral biopsy samples from patients with various OPMDs, including oral leukoplakia (OLK), proliferative verrucous leukoplakia (PVL), oral lichen planus (OLP), and oral lichenoid lesions (OLL).

Additionally, samples were collected from patients with proliferative verrucous leukoplakia (PVL) who had progressed to squamous cell carcinoma (SCC) and from a control group of healthy individuals. DNA was extracted from these samples, and 2bRAD-M sequencing was used to determine the taxonomic profiles of the microbial communities present.

Analysis revealed significant differences in the richness and diversity of microbial communities across the different OPMD groups. Notably, OLK samples showed the highest microbial richness, while the microbial profiles of PVL-SCC samples resembled those of the healthy controls. Each disease group displayed a unique microbial composition, with distinct dominant bacterial species identified. The progression from PVL to SCC was marked by a decrease in Fusobacterium periodonticum and an increase in Prevotella oris.

The study highlighted the distinct nature of microbial communities in different OPMDs. The unique microbial compositions and dominant species identified for each disorder suggest these microbes could contribute to disease development. Further investigation into these differences may provide insights into the pathogenesis of these disorders.

Funding support was provided by the National Nature Science Foundation of China (China, grant numbers 81671006, 81300894,81000440), CAMS Innovation Fund for Medical Sciences (China, grant number 2019-I2M-5-038), National Clinical Key Discipline Construction Project (China, PKUSSNKP-202102).

Source: https://pubmed.ncbi.nlm.nih.gov/39223464/

Zhou X, Cai X, Tang Q, et al. (2024). “Differences in the landscape of colonized microorganisms in different oral potentially malignant disorders and squamous cell carcinoma: a multi-group comparative study.” BMC Microbiol. 2024;24(1):318. Published 2024 Sep 2. doi:10.1186/s12866-024-03458-3

CONUT Score’s Prognostic Value in HNC: A Meta-Analysis

KEY TAKEAWAYS

  • This meta-analysis aimed to evaluate the prognostic value of the CONUT score for patients with HNC.
  • Results revealed that a high CONUT score is significantly associated with poor OS and DFS in patients with HNC.

The CONUT score is a simple and cost-effective tool for assessing nutritional status, which is known to influence cancer prognosis. While some studies have investigated the CONUT score in head and neck cancer (HNC), the findings have been inconsistent, prompting this meta-analysis.

Yanyan Wang and the team aimed to evaluate the prognostic accuracy of the CONUT score in predicting overall survival (OS) and disease-free survival (DFS) in patients with HNC.

Researchers conducted a meta-analysis of studies investigating the relationship between CONUT score and HNC prognosis. They calculated pooled HRs and 95% CIs to assess the effect of CONUT score on OS and DFS. They also investigated the correlation between CONUT score and clinicopathological features using combined odds ratios (ORs) and 95% CIs. A fixed-effects model was used due to non-significant heterogeneity.

About 8 studies, including 1,478 patients, were included in the analysis.The results demonstrated a significant association between a high CONUT score and poor OS (HR= 1.94, 95% CI= 1.55-2.44, P< 0.001) and DFS (HR= 1.93, 95% CI= 1.45-2.56, P< 0.001).

Furthermore, a higher CONUT score correlated significantly with advanced T stage (T3-T4) (OR= 3.21, 95% CI= 1.94-5.31, P< 0.001) and N stage (N1-N3) (OR= 3.10, 95% CI= 1.74-5.53, P< 0.001).

This meta-analysis suggested that the CONUT score is a valuable prognostic indicator for patients with HNC. A high CONUT score is strongly associated with worse OS and DFS, as well as advanced tumour stage and lymph node metastasis. The CONUT score, being readily available and cost-effective, can be a promising prognostic biomarker for HNC.

No funding was provided.

Source: https://pubmed.ncbi.nlm.nih.gov/39192261/

Wang Y, Qian C. (2024). “Prognostic and clinicopathological value of the controlling nutritional status (CONUT) score in patients with head and neck cancer: a meta-analysis.” World J Surg Oncol. 2024;22(1):223. Published 2024 Aug 27. doi:10.1186/s12957-024-03505-3

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