Erratum: Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.54014.].

Development of a novel prognostic signature derived from essential genes in head and neck squamous cell carcinoma.

BACKGROUND: Substantial heterogeneity in head and neck squamous cell carcinoma (HNSCC) compromise accurate patient stratification and personalized treatment planning. Current molecular classification is largely based on genes with highly variable expression without considering their functional roles. Here, we sought to identify HNSCC essential genes for patient stratification and prognostication. METHODS: Essential genes for HNSCC were screened from genome-wide CRISPR knockout datasets. Candidates were further identified through univariate Cox regression. The least absolute shrinkage and selection operator was utilized to develop the prognostic signature. Candidate essential genes were exploited to classify patients into subgroups by consensus clustering. Survival outcomes, genomic alterations, signaling activities, and therapeutic vulnerabilities were compared between patient subgroups. RESULTS: Sixty-eight genes were identified as candidates and utilized to develop an 8-gene prognostic signature. Patients were segregated into two clusters with distinct survival rates across multiple cohorts based on upregulated essential genes. Cluster 2 exhibited higher TP53, CDKN2A, and NOTCH1 mutations, higher stromal activities, worse prognosis as well as and sensitivities to cell cycle inhibitors. Cluster 1 was characterized by a better prognosis and susceptibility to PI3K/AKT and MAPK inhibitors. CONCLUSION: Our study developed a novel and robust prognostic signature and classification derived from essential genes for HNSCC, which sheds new light on HNSCC precision oncology.

Development of a novel signature derived from single cell RNA-sequencing for preoperative prediction of lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is considered as an adverse prognostic indicator for cancer patients. Preoperative knowledge of LNM is valuable for pretreatment decision making. Here, we sought to develop and validate an LNM signature for preoperative prediction of LNM in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: By studying single cell RNA-sequencing data (scRNA-seq), differentially expressed mRNA were selected and analyzed through univariate logistic regression and least absolute shrinkage and selection operator (LASSO) to identify an LNM signature. Multivariate logistic regression was utilized to establish an LNM nomogram incorporating LNM signature and T-classification. RESULTS: The LNM signature was significantly associated with lymph node status and prognosis. The LNM signature and LNM nomogram displayed a robust predictive effect. CONCLUSION: Our study reveals that LNM signature is a powerful biomarker for preoperative prediction of LNM in patients with HNSCC, which may be effective to realize individualized outcome prediction.

Regulation of Semaphorin3A in the process of cutaneous wound healing.

Semaphorin 3A (Sema3A) has been recognized as a crucial regulator of morphogenesis and homeostasis over a wide range of organ systems. However, its function in cutaneous wound healing is poorly understood. In our study, we demonstrated that Sema3A adenovirus plasmids transfection limited keratinocyte proliferation and decreased migrative capacity as assessed by in vitro wound healing assay. Sema3A transduction inhibited TGF-ß1-mediated keratinocyte migration and EMT process. Besides, we applied mice with K14-Cre-mediated deletion of Sema3A and found that Sema3A depletion postponed wound closure with decreased re-epithelialization and matrix growth. Contrary to the results obtained with full-length Sema3A plasmids transfection, increased keratinocyte migration with recombinant Sema3A proteins resulted in quicker closure of the wounding area after a scratch. Further, exogenously applied recombinant Sema3A worked with EGF to maintain the activation of EGFR by interacting with NRP1 and thereby regulated the internalization of the EGFR-NRP1 complex. Taken together, these results indicated a paradoxical role of autonomous and non-autonomous Sema3A expression during wound healing. Combined administration of recombinant EGF and Sema3A proteins could accelerate the process of wound repair, thus providing promising treatment prospects in the future.

Sarcopenia and perioperative management of elderly surgical patients.

Sarcopenia is the age-related loss of skeletal muscle mass, accompanied by reduced muscle strength or physical function. As the global population continues to age, the prevalence of sarcopenia is gradually increasing. It is conceivable that an increasing number of patients with sarcopenia will be scheduled for surgery and anesthesia in the near future. The complex pathogenesis and clinical features of sarcopenia have brought huge challenges to perioperative management, especially in clinical anesthesia. However, there are currently neither guidelines nor expert consensus on the perioperative management of patients with sarcopenia. In this review, we summarize and elaborate on the pathogenesis, diagnosis, and perioperative precautions of sarcopenia, thereby providing information on the perioperative and anesthestic management of patients with sarcopenia.

Ubiquitin D Promotes Progression of Oral Squamous Cell Carcinoma via NF-Kappa B Signaling.

Ubiquitin D (UBD) is highly upregulated in many cancers, and plays a pivotal role in the pathophysiological processes of cancers. However, its roles and underlying mechanisms in oral squamous cell carcinoma (OSCC) are still unclear. In the present study, we investigated the role of UBD in patients with OSCC. Quantitative real-time polymerase chain reaction and Western blot were used to measure the expression of UBD in OSCC tissues. Immunohistochemistry assay was used to detect the differential expressions of UBD in 244 OSCC patients and 32 cases of normal oral mucosae. In addition, CCK-8, colony formation, wound healing and Transwell assays were performed to evaluate the effect of UBD on the cell proliferation, migration, and invasion in OSCC. Furthermore, a xenograft tumor model was established to verify the role of UBD on tumor formation in vivo. We found that UBD was upregulated in human OSCC tissues and cell lines and was associated with clinical and pathological features of patients. Moreover, the overexpression of UBD promoted the proliferation, migration and invasion of OSCC cells; however, the knockdown of UBD exerted the opposite effects. In this study, our results also suggested that UBD promoted OSCC progression through NF-κB signaling. Our findings indicated that UBD played a critical role in OSCC and may serve as a prognostic biomarker and potential therapeutic target for OSCC treatment.

Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response.

BACKGROUND: Immune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune cells (TIIs) in primary oral squamous cell carcinoma (OSCC) and develop immune features-derived models for prognostication and therapeutic prediction. METHODS: A total number of 392 patients with OSCC receiving ablative surgery at three independent centers were retrospectively enrolled and defined as training, testing and validation cohorts. Detailed features of 12 types of TIIs at center of tumor and invasive margin were assessed by immunohistochemistry coupled with digital quantification. TIIs abundance in OSCC was also estimated by bioinformatics approaches using multiple publicly available data sets. Prognostic models based on selected immune features were trained via machine learning approach, validated in independent cohorts and evaluated by time-dependent area under the curves and concordance index (C-index). Immune types of OSCC were further identified by consensus clustering and their associations with genetic, molecular features and patient survival were clarified. RESULTS: Patterns of TIIs infiltration varied among patients and dynamically evolved along with tumor progression. Prognostic models based on selected TIIs were identified as efficient and sensitive biomarkers to stratify patients into subgroups with favorable or inferior survival as well as responders or non-responders to postoperative radiotherapy or immunotherapy. These models outperformed multiple conventional biomarkers and immune-related scores in prognostic prediction. Furthermore, we identified two main immune subtypes of OSCC (immune-hot and immune-cold) which harbored characteristic TIIs infiltrations and genomic and molecular features, and associated with patient survival. CONCLUSIONS: Our results delineated immune landscape and subtypes in OSCC, consolidated their clinical values as robust biomarkers to predict patient survival and therapeutic benefits and reinforced key roles of TIIs and tumor-immune interactions underlying oral tumorigenesis, ultimately facilitating development of tailed immunotherapeutic strategies.

Involvement of miR-619-5p in resistance to cisplatin by regulating ATXN3 in oral squamous cell carcinoma.

MicroRNAs are major post-transcriptional regulators responsible for the development of human cancers, including OSCC. The specific role of miR-619-5p in OSCC, however, is rarely reported. Cisplatin is one of the mostly applied chemotherapy drugs of OSCC. Nevertheless, drug resistance of cisplatin following the initial chemotherapy largely restricts its clinical benefits, and the mechanism of cisplatin resistance is unclear. This study intends to explore the biological function of miR-619-5p in the development of cisplatin resistance in OSCC cell lines and a xenograft model, as well as the potential molecular mechanism. Our results showed that miR-619-5p was down-regulated in OSCC samples and cisplatin-resistant OSCC cells. Ectopically expressed miR-619-5p inhibited proliferative, migratory and invasive abilities of OSCC cisplatin-resistant cells. The putative target gene ATXN3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Importantly, ATXN3 was responsible for the regulatory effects of miR-619-5p on biological behaviors of cisplatin-resistant OSCC cells. Moreover, miR-619-5p mimics and ATXN3-siRNA significantly enhanced ATXN3 knockdown in both HN6/CDDPR and CAL27/CDDPR cells and inhibited expression of PI3K and AKT. In vivo evidences demonstrated that intratumoral injection of miR-619-5p agomir remarkably slowed down the growth of OSCC in xenograft mice. Collectively, microRNA-619-5p was the vital regulator for regulating cisplatin resistance of OSCC, which may be served as a potential therapeutic target.

Perioperative neurocognitive dysfunction: thinking from the gut?

With the aging of the world population, and improvements in medical and health technologies, there are increasing numbers of elderly patients undergoing anaesthesia and surgery. Perioperative neurocognitive dysfunction has gradually attracted increasing attention from academics. Very recently, 6 well-known journals jointly recommended that the term perioperative neurocognitive dysfunction (defined according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition) should be adopted to improve the quality and consistency of academic communications. Perioperative neurocognitive dysfunction currently includes preoperatively diagnosed cognitive decline, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction. Increasing evidence shows that the gut microbiota plays a pivotal role in neuropsychiatric diseases, and in central nervous system functions via the microbiota-gut-brain axis. We recently reported that abnormalities in the composition of the gut microbiota might underlie the mechanisms of postoperative cognitive dysfunction and postoperative delirium, suggesting a critical role for the gut microbiota in perioperative neurocognitive dysfunction. This article therefore reviewed recent findings on the linkage between the gut microbiota and the underlying mechanisms of perioperative neurocognitive dysfunction.