Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis-Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment.

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well-established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading-edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF-derived OSCC tissues. This work reveals for the first time that some OSF-derived OSCC cells undergo partial epithelial-mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast-like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF-derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF-derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

Spatially Resolved Transcriptomics Technology Facilitates Cancer Research.

Single cell RNA sequencing (scRNA-seq) provides a great convenience for studying tumor occurrence and development for its ability to study gene expression at the individual cell level. However, patient-derived tumor tissues are composed of multiple types of cells including tumor cells and adjacent non-malignant cells such as stromal cells and immune cells. The spatial locations of various cells in situ tissues plays a pivotal role in the occurrence and development of tumors, which cannot be elucidated by scRNA-seq alone. Spatially resolved transcriptomics (SRT) technology emerges timely to explore the unrecognized relationship between the spatial background of a particular cell and its functions, and is increasingly used in cancer research. This review provides a systematic overview of the SRT technologies that are developed, in particular the more widely used cutting-edge SRT technologies based on next-generation sequencing (NGS). In addition, the main achievements by SRT technologies in precisely unveiling the underappreciated spatial locations on gene expression and cell function with unprecedented high-resolution in cancer research are emphasized, with the aim of developing more effective clinical therapeutics oriented to a deeper understanding of the interaction between tumor cells and surrounding non-malignant cells.

Potential applications of N6 -methyladenosine modification in the prognosis and treatment of cancers via modulating apoptosis, autophagy, and ferroptosis.

N6 -methyladenosine (m6 A) is one of the most abundant modifications determining the fate of RNA. Currently, m6 A modification is tightly connected with tumorigenesis and presents novel promise in clinical applications. Regulated cell death (RCD) is a programmed mechanism that plays a complicated role in malignant transition. Regarding the main forms of RCD, aberrant levels of m6 A modification have been detected during the progression of apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis in several diseases. However, few reviews have elucidated the correlation between m6 A-modified RCD and carcinogenesis. In this review, we summarize the regulators of m6 A methylation and their functions in carcinogenesis through an overview of m6 A-modified RCD. Additionally, we assume the potential role of m6 A modification regulators as novel biomarkers for chemotherapies and precision medicine. Furthermore, we review the controversies and conflicts in m6 A explorations and predict future orientations of m6 A-modified RCD for clinical applications. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Reconstruction of Complex Lateral Skull Base Defects After Oral Cancer Resection With Individualized Anterolateral Thigh Flap.

OBJECTIVES: Complex lateral skull base defects resulting from advanced or recurrent oral cancer resection are continuously challenging reconstructive surgeons. This study aimed to use reconstructive methods for lateral skull base defects, explore their feasibility, and evaluate the efficacy of defect reconstruction using anterolateral thigh (ALT) flaps. PATIENTS AND METHODS: We performed a retrospective case series of 37 patients who underwent lateral skull base defect reconstruction using the ALT/anteromedial thigh (AMT) flap between March 2016 and May 2021 at the Second Xiangya Hospital. The design and harvest of the flaps, methods for defect reconstruction, and reconstructive efficacy are described. RESULTS: Of the 37 patients, 3 were women and 34 were men, with a mean age of 51.7 years. Among the defects, 26 were through-and-through defects and were reconstructed using ALT chimeric flaps, double ALT flaps, folded ALT flap, combined ALT chimeric flaps and AMT flaps, or combined ALT chimeric flaps and pectoralis major flaps; the large lateral skull base dead spaces were filled with muscle tissues or fatty tissues. Postoperatively, 38 of the 39 ALT/AMT flaps survived completely, and the remaining flap experienced partial necrosis. Venous compromise occurred in one patient who was salvaged after operative exploration. Oral and maxillofacial wound infections occurred in two patients, salivary fistula in three patients, and thigh wound effusion in three patients. The wounds healed gradually in all patients after repeated dressing changes. Thirty-three patients were followed up for approximately 3-60 months; their oral functions and appearance were acceptable, and thigh motor dysfunction was not observed. CONCLUSIONS: With the convenient flap design and muscle flap harvest, large and individualized tissue supply, feasible combination with other flaps, effective reduction or avoidance of wound complications, and acceptable donor site morbidity, the ALT flap is an appropriate choice for complex lateral skull base defect reconstruction.