Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study.

INTRODUCTION: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20%-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. AIM: To construct and evaluate a preoperative diagnostic method to predict occult lymph node metastasis (OCLNM) in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. METHODS: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA) and survival analysis. RESULTS: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927) and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1 and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. CONCLUSION: The proposed MRI-based Resnet50 deep learning model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

Medial sural artery perforator free flap versus radial forearm free flap in oral cavity reconstruction and donor site morbidity.

OBJECTIVE: Radial Forearm Free flap (RFFF) is widely used in head and neck reconstruction, yet its donor site defect remains a significant drawback. The Medial Sural Artery Perforator Free Flap (MSAPFF) is considered an alternative flap to RFFF. This study aims to comprehensively analyze their characteristics, outcomes, and their impact on patient quality of life. METHODS: All patients who underwent oral cavity reconstruction using RFFF and MSAPFF between February 2017 and April 2023 were included in this study. Flap characteristics, outcomes and post-operative complications were recorded and compared. Subjective donor site morbidity, aesthetic and functional results, and quality of life were also analyzed. RESULTS: The study included 76 patients: 37 underwent reconstruction with RFFF, and 39 with MSAPFF. There was no significance difference between the RFFF and MSAPFF regarding the success rate (97.2% vs 97.4%), flap size (4.8 × 8.8 cm2 vs 5 × 9.8 cm2), hospital of stay (15.5 days vs 13.5 days) and recipient site complications (P > 0.05). However, MSAPFF showed larger flap thickness (P = 0.001), smaller arterial caliber (P = 0.008), shorter pedicle length (P = 0.001), and longer harvesting time (P < 0.001). No significant difference was observed between the pre-and postoperative ranges of wrist and ankle movements or in recipient site complications. MSAPFF showed a significant difference in donor site morbidity (P < 0.05). CONCLUSION: The MSAPFF is an excellent alternative to the RFFF for repairing oral cavity defects, with additional advantage of a well-hidden scar on the posterior calf, a larger flap thickness, accepted pedicle length and arterial caliber. However, one should consider the harvesting time and surgical skills required in comparison to the RFFF. CLINICAL RELEVANCE: The study highlights the importance of the MSAPFF as an alternative option for RFFF with less donor site morbidity and high success rate in oral cavity reconstruction and improved patient Quality of life after ablative surgery.

Senp7 deficiency impairs lipid droplets maturation in white adipose tissues via Plin4 deSUMOylation.

Lipid metabolism is important for the maintenance of physiological homeostasis. Several members of the small ubiquitin-like modifier (SUMO)-specific protease (SENP) family have been reported as the regulators of lipid homeostasis. However, the function of Senp7 in lipid metabolism remains unclear. In this study, we generated both conventional and adipocyte-specific Senp7 KO mice to characterize the role of Senp7 in lipid metabolism homeostasis. Both Senp7-deficient mice displayed reduced white adipose tissue mass and decreased size of adipocytes. By analyzing the lipid droplet morphology, we demonstrated that the lipid droplet size was significantly smaller in Senp7-deficient adipocytes. Mechanistically, Senp7 could deSUMOylate the perilipin family protein Plin4 to promote the lipid droplet localization of Plin4. Our results reveal an important role of Senp7 in the maturation of lipid droplets via Plin4 deSUMOylation.

To die or not to die: Gasdermins in intestinal health and disease.

Intestinal homeostasis is achieved by the balance among intestinal epithelium, immune cells, and gut microbiota. Gasdermins (GSDMs), a family of membrane pore forming proteins, can trigger rapid inflammatory cell death in the gut, mainly pyroptosis and NETosis. Importantly, there is increasing literature on the non-cell lytic roles of GSDMs in intestinal homeostasis and disease. While GSDMA is low and PJVK is not expressed in the gut, high GSDMB and GSDMC expression is found almost restrictively in intestinal epithelial cells. Conversely, GSDMD and GSDME show more ubiquitous expression among various cell types in the gut. The N-terminal region of GSDMs can be liberated for pore formation by an array of proteases in response to pathogen- and danger-associated signals, but it is not fully understood what cell type-specific mechanisms activate intestinal GSDMs. The host relies on GSDMs for pathogen defense, tissue tolerance, and cancerous cell death; however, pro-inflammatory milieu caused by pyroptosis and excessive cytokine release may favor the development and progression of inflammatory bowel disease and cancer. Therefore, a thorough understanding of spatiotemporal mechanisms that control gasdermin expression, activation, and function is essential for the development of future therapeutics for intestinal disorders.

Fibular free flap necrosis after mandibular reconstruction surgery with osteoradionecrosis: Establishment and verification of an early warning model.

OBJECTIVE: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients. METHODS: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation. RESULTS: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest. CONCLUSION: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value.

Modified submandibular mandibulotomy approach versus lip-splitting approach in tongue cancer surgery: a retrospective paired-cohort study.

OBJECTIVES: The surgical approach for resection and reconstruction of tongue cancer (TSCC) with or without the lip-splitting incision is controversial. This study introduced a modified approach without lip-splitting and the clinical results were assessed. METHODS: Sixty-eight TSCC patients underwent surgery using the modified submandibular mandibulotomy (MSMM) approach without lip-splitting, and another matched 68 patients using lip-splitting mandibulotomy (LSM) approach were enrolled in this study. The clinical results including intraoperative relevance and surgical morbidities, survival status, facial appearance and scar scores, function of lower lip, and quality of life (QOL) were evaluated. RESULTS: The primary tumors were en bloc resected through the MSMM approach with excellent tumor exposure and R0 resection margins as LSM approach. The survival status and complications were similar in both groups. The function of lower lip was better in patients of MSMM group at 1 month after surgery. The MSMM approach was associated with significantly better facial appearance and recreation compared to LSM approach by scar scores and QOL assessment. CONCLUSION: The MSMM approach without lip-splitting achieves similar tumor control, better aesthetic results, and QOL compared to LSM approach. It is a safe and effective surgical approach for patients with TSCC. CLINICAL RELEVANCE: The MSMM approach without lip-splitting is oncological safety in tongue cancer surgery and is scrutinized as one part of the treatment concept for better aesthetic results.

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway.

Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. We found that Gsdma1/2/3 KO mice showed significantly decreased epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, we found that the alleviation of epidermal hyperplasia depends on Gsdma1/2/3 expressed specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.

Intratumoral CD103+ CD8+ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma.

BACKGROUND: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. METHODS: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103+ CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+ CD8+ TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images. RESULTS: We established intratumoral CD103+ CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103+ CD8+ TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+ CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+ CD8+ TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103+ CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2+ ) macrophages might enhance the population of CD103+ CD8+ TILs and facilitate antitumor immunity during NACI treatment. CONCLUSIONS: Our study highlights the impact of intratumoral CD103+ CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

Is the retromandibular approach a suitable approach to anatomical reduction of unilateral subcondylar fracture? A non-randomized clinical trial.

The aim of this study was to evaluate the efficacy of the retromandibular approach (RMA) to produce three-dimensional (3-D) reduction of the unilateral subcondylar fracture and Temporomandibular Joint (TMJ) functional implication. METHODS:  A prospective cohort study was designed. Twenty-nine patients with unilateral subcondylar fracture underwent consecutively Open Reduction, and Internal Fixation. The cohorts were divided into two groups; RMA group (n = 16, 55.17%) and submandibular approach SMA group (n = 13, 44.82%). The primary outcome was the anatomical 3-D reduction of the condyle. The secondary outcome was to compare the condyle position and inclination finding with TMJ outcomes. Helkimo Index score was used to evaluate the TMJ outcome at six months postoperatively. RESULT:  There was a significant difference between the mediolateral condylar inclination, condylar medial and vertical positions when RMA compared with SMA groups (P < 0.05). The medial joint space was correlated with the medial condylar position in both groups (P < 0.05). The Helkimo Ai and Di was associated with mediolateral condylar inclination in SMG; however, Helkimo Ai was found to be correlated with the RMA group. CONCLUSION:  The current study demonstrates that the RMA could re-establish the anatomical position of the unilateral subcondylar fracture in patients undergoing ORIF. The clinical outcome of the TMJ with RMA was better than SMA.

Tumor-Associated Macrophages Promote Metastasis of Oral Squamous Cell Carcinoma via CCL13 Regulated by Stress Granule.

M2 tumor-associated macrophages (TAMs) have been a well-established promoter of oral squamous cell carcinoma (OSCC) progression. However, the mechanisms of M2 TAMs promoting OSCC metastasis have not been elucidated clearly. This study illustrated the regulatory mechanisms in which M2 TAMs enhance OSCC malignancy in a novel point of view. In this study, mass spectrometry was utilized to analyze the proteins expression profile of M2 type monocyte-derived macrophages (MDMs-M2), whose results revealed the high expression of G3BP1 in M2 macrophages. RNA sequencing analyzed the genome-wide changes upon G3BP1 knockdown in MDMs-M2 and identified that CCL13 was the most significantly downregulated inflammatory cytokines in MDMs-M2. Co-immunoprecipitation and qualitative mass spectrometry were used to identify the proteins that directly interacted with endogenous G3BP1 in MDMs-M2. Elevated stress granule (SG) formation in stressed M2 TAMs enhanced the expression of CCL13, which promoted OSCC metastasis both in vitro and in vivo. For mechanisms, we demonstrated SG formation improved DDX3Y/hnRNPF-mediated CCL13 mRNA stability, thus enhancing CCL13 expression and promoting OSCC metastasis. Collectively, our findings demonstrated for the first time the roles of CCL13 in improving OSCC metastasis and illustrated the molecular mechanisms of CCL13 expression regulated by SG, indicating that the SG-CCL13 axis can be the potential targets for TAM-navigated tumor therapy.

Retraction Notice to: lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-ß-Induced Epithelial-Mesenchymal Transition.

[This retracts the article DOI: 10.1016/j.omtn.2020.08.003.].

Circ-OMAC drives metastasis in oral squamous cell carcinoma.

OBJECTIVES: Accumulating studies have proved that the circular RNAs (circRNAs) play vital roles in human cancers. However, few circRNAs have been elucidated with lymph node metastasis. This study demonstrated that circ-oral cancer metastasis-associated circRNA (circ-OMAC) is required to regulate the oral squamous cell carcinoma (OSCC) metastasis. MATERIALS AND METHODS: The circ-OMAC were detected by circRNA-sequencing and further verified by in situ hybridization (ISH). The role of circ-OMAC was assessed by transwell assay and wound healing assay. Mechanistically, circ-OMAC regulated OSCC metastasis by initiating the epithelial-to-mesenchymal transition (EMT) signaling pathway. RESULTS: Our findings suggested that circ-OMAC was aberrantly elevated in the metastatic lymph nodes as compared to primary OSCC tissues. OSCC patients with high levels of circ-OMAC were prone to a poor prognosis. By developing functional assays, we confirmed that circ-OMAC promotes metastasis of OSCC cells via initiation of EMT pathways. CONCLUSIONS: We provide new insights whereby Circ-OMAC as an oncogene is a potential therapeutic target and prognostic marker in oral cancer.

Overexpressed LINC01510 Attenuates Epithelial-Mesenchymal Transition in High Glucose-Induced Renal Tubular Epithelial Cells via Inactivating MMP7.

OBJECTIVE: Matrix metallopeptidase 7 (MMP7) can promote renal fibrosis in diabetic kidney disease (DKD). A study found that LINC01510 overexpression inhibits MMP7 to play a role in renal cancer, but the relationship between the two in DKD had not been revealed, and the function of LINC01510 also needed to be explored, which was also the focus of this study. METHODS: The morphological changes of HK-2 cells induced by high glucose were observed by an inverted microscope, and fluorescence in situ hybridization was used to determine the subcellular localization of LINC01510. Quantitative realtime polymerase chain reaction was used to detect the levels of LINC01510 and MMP7. The effect of LINC01510 and MMP7 overexpression on high glucose-induced HK-2 cell migration and epithelial-mesenchymal transition (EMT)-related protein changes was confirmed by wound healing experiments and western blot. RESULTS: High glucose induced HK-2 cells to gradually lose their epithelial phenotype, and decreased LINC01510 in a time-dependent manner. LINC01510 was located in the nucleus of HK-2 cells. LINC01510 overexpression increased the level of LINC01510, inhibited cell migration, and reduced the expression of MMP-7, Vimentin, α-SMA, and Fibronectin protein, and promoted the expression of E-cadherin protein in high glucose-induced cells. The effect of MMP7 overexpression on migration and EMT-related proteins was opposite to the effect of LINC01510 overexpression, and partially reversed the effect of LINC01510 overexpression in high glucose-induced cells. CONCLUSION: Our research shows that LINC01510 overexpression inactivates MMP7 to attenuate high glucose-induced EMT of renal tubular epithelial cells.

The interaction between STING and NCOA4 exacerbates lethal sepsis by orchestrating ferroptosis and inflammatory responses in macrophages.

The discovery of STING-related innate immunity has recently provided a deep mechanistic understanding of immunopathy. While the detrimental effects of STING during sepsis had been well documented, the exact mechanism by which STING causes lethal sepsis remains obscure. Through single-cell RNA sequence, genetic approaches, and mass spectrometry, we demonstrate that STING promotes sepsis-induced multiple organ injury by inducing macrophage ferroptosis in a cGAS- and interferon-independent manner. Mechanistically, Q237, E316, and S322 in the CBD domain of STING are critical binding sites for the interaction with the coiled-coil domain of NCOA4. Their interaction not only triggers ferritinophagy-mediated ferroptosis, but also maintains the stability of STING dimers leading to enhanced inflammatory response, and reduces the nuclear localization of NCOA4, which impairs the transcription factor coregulator function of NCOA4. Meanwhile, we identified HET0016 by high throughput screening, a selective 20-HETE synthase inhibitor, decreased STING-induced ferroptosis in peripheral blood mononuclear cells from patients with sepsis and mortality in septic mice model. Our findings uncover a novel mechanism by which the interaction between STING and NCOA4 regulates innate immune response and ferroptosis, which can be reversed by HET0016, providing mechanistic and promising targets insights into sepsis.

Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C.

The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.

Comparison of postoperative cytokine and hormone between endoscopically assisted and open parotid tumor resection.

OBJECTIVE: Endoscopically assisted extracapsular dissection through a single incision along the cephaloauricular furrow has been adapted as a method of access for operating on benign parotid gland tumors. However, no study has compared the immune and stress responses after surgery between the endoscopic procedure and conventional open surgery. METHODS: Through a randomized method, 50 patients with benign parotid gland tumors were assigned to undergo either endoscopically assisted extracapsular dissection or open parotidectomy. The postoperative inflammatory changes and hormonal response in the patients were analyzed at serum level during the preoperative period and at 12, 24, and 72 hr after either surgery. RESULTS: Twenty-three patients received an endoscopic procedure, while 27 underwent open surgery. The size of the incision, amount of intraoperative bleeding, volume of drainage, postoperative pain score, and satisfaction with appearance were all improved in the endoscopic procedure group. Additionally, the serum levels of C-reactive protein, interleukin (IL)-6, IL-10, and cortisol were significantly lower in the endoscopy group in comparison with those in the open surgery group. CONCLUSION: Endoscopically assisted extracapsular dissection on patients with benign parotid gland tumors is associated with lower inflammatory changes and hormone responses than open surgery, thereby reducing perioperative pathophysiological disturbance and enhancing recovery after surgery.

The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study.

OBJECTIVE: Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC). METHODS: TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups. RESULTS: High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients. CONCLUSIONS: HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration.

lncRNA lnc-TSI Inhibits Metastasis of Clear Cell Renal Cell Carcinoma by Suppressing TGF-ß-Induced Epithelial-Mesenchymal Transition.

The transforming growth factor-ß (TGF-ß)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-ß/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-ß/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-ß/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis in vitro and ccRCC lung metastasis in vivo, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-ß receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs.

Full cheek defect reconstruction using ALTF versus RFF: Comparison of quality of life, clinical results, and donor site morbidity.

OBJECTIVES: This study aimed to compare the quality of life (QOL) of patients, clinical results of the recipient site, and morbidities of the donor site between the use of free anterolateral thigh flaps (ALTFs) and radial forearm flaps (RFFs) for reconstruction of full cheek defects following tumor resection. MATERIALS AND METHODS: We retrospectively reviewed 52 patients who underwent reconstruction of full cheek defects using free ALTFs and free RFFs following tumor ablation at our center. The range of mouth opening, speech, swallowing, facial appearance, donor site complications, and subjective symptoms based on the University of Washington Quality of Life (UW-QOL) questionnaire findings were assessed in the ALTF and RFF groups at 3, 12, and 36 months after surgery. RESULTS: Quality of life, range of mouth opening, facial appearance, mood and anxiety, donor site appearance, subjective feeling, and functional impairment were better in the ALTF group than in the RFF group based on the physical examination findings and questionnaire scores. CONCLUSION: This study found better QOL and better functional results at the recipient site and minor morbidities at the donor site with the use of free ALTFs in the reconstruction of full cheek defects.