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Purpose: The study aimed to retrospectively identify the prognostic factors of surgically treated primary tongue squamous cell carcinoma (TSCC) cases and assess the benefits of surgical neck lymph node dissection (LND) in early‐stage cancer. Methods: Patients with primary TSCC with pT1‐2N0‐1M0 stage without distant metastasis who were treated with surgery during 2014–2016 at Xiangya Hospital, Central South University were included. Univariate and multivariate Cox models were constructed to explore prognostic factors of overall survival (OS), disease‐free survival (DFS), and local recurrence‐free survival (LRFS). Sub‐group analysis was used to assess the effect of adjuvant therapy and the prognostic value of LND for the early‐stage patients. Results: In total, 440 patients met the inclusion criteria. During the follow‐up period, the 5‐year OS, DFS, were 84.4% and 70.0%, respectively. Univariate analysis showed that TNM stage, lymphovascular invasion (LVI), and/or perineural invasion (PNI), pathological differentiation, etc. were significant predictors of OS and DFS. Multivariate analysis showed that TNM stage and the degree of pathological differentiation were independent prognostic factors for all outcomes. Besides, the number of cervical LND could independently predict both DFS and LRFS while LVI/PNI were associated with DFS. And high‐quality neck LND (≥30) significantly improved DFS and LRFS for patients of pT1cN0M0 or stage I as compared to those without LND. Conclusions: TNM stage and pathological differentiation were crucial prognostic factors for postoperative patients with TSCC. Notably, high‐quality cervical LND was beneficial for the improvement of DFS and LRFS for patients of pT1cN0M0 or stage I. [ABSTRACT FROM AUTHOR]

Phosphoinositide‐3 kinase alpha (PI3Kα) has been confirmed to be a potential therapeutic target for esophageal squamous cell carcinoma (ESCC), while the potency of PI3Kα inhibitors is often attenuated by concurrent oncogenic signalling pathways. We performed genome‐wide gain‐of‐function screening with a CRISPR‐SAM library and identified enhancer of zeste homolog 2 (EZH2) rendering ESCC cells resistant to the PI3Kα inhibitor CYH33. Enhanced expression of EZH2 frequently occurs in ESCC and is related to poor prognosis. Overexpression of full‐length EZH2 but not methyltransferase‐deficient EZH2 conferred resistance to CYH33, while downregulating EZH2 expression restored sensitivity. EZH2 expression was negatively related to the activity of CYH33 against the proliferation of ESCC cell lines and patient‐derived cells. Transcriptomic analysis revealed that EZH2 abrogated CYH33‐mediated cell cycle regulation. EZH2 epigenetically suppressed the transcription of CDKN1A, promoting RB phosphorylation and cell cycle progression. Concurrently targeting EZH2 significantly potentiated CYH33 to inhibit the growth of ESCC cells and patient‐derived xenografts accompanied by enhanced cell cycle arrest. Taken together, our study demonstrated that an EZH2‐p21‐RB axis remodeled cell cycle regulation and rendered resistance to PI3Kα inhibitors in ESCC. Simultaneously targeting PI3Kα and EZH2 may provide an effective strategy for ESCC therapy with high expression of EZH2. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two subtypes of esophageal cancer with diverse epidemiology and pathogenesis as well as different molecular profiles. This review analyzes the genomic alterations in ESCC and EAC and summarizes the potential therapeutic targets of ESCC and EAC. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1-3N0M0 ESCC.Methods: Patients with pT1-3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially.Results: This study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001).Conclusions: Several factors were associated with the survival of patients with pT1-3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. Patients with ESCC have poor long-term survival, especially those with lymphatic metastasis (pN + ESCC). In this retrospective study, we evaluated the correlates of long-term survival time of patients with pN + ESCC. A total of 453 patients with pN + ESCC who underwent surgical R0 resection between Jan 2008 and Sep 2011 were enrolled. The follow-up ended on December 2019. The clinical, pathological, inflammation-related factors and general survival data of these patients were analyzed using SPSS 22.0 software. The 1-, 3-, and 5-year overall survival (OS) rates were 73.7%, 34.6%, and 25.6%, respectively; the 1-, 3-, and 5-year disease-free survival (DFS) rates were 45.0%, 26.3%, and 20.4%, respectively. The median OS and DFS were 23 and 14 months, respectively. On multivariate analyses, gender, site of lesion, number of dissected lymph nodes, stage pTNM, adjuvant therapy, and neutrophil lymphocyte ratio were independent predictors of OS. Site of lesion, stage pTNM, and adjuvant therapy were independent predictors of DFS. Recursive partitioning analysis (RPA) scores of each patient were calculated based on the independent predictors of OS, and the patients were divided into 3 classes: low-risk, medium-risk, and high-risk. The OS, DFS, and local recurrence-free survival were significantly different among these three RPA classes P < 0.001 . Several factors showed an independent association with long-term postoperative survival of pN + ESCC patients after radical surgery. RPA scores can potentially be used to predict the prognosis of ESCC. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. However, patient survival time after surgery remains unsatisfactory, especially in those who are pN+. This retrospective study determined the value of postoperative adjuvant therapy for patients with pN+ ESCC. From Jan 2008 to Sep 2011, 453 pN+ ESCC patients who underwent R0 resection and survived for at least 1 month were retrospectively enrolled. All patients received surgery. Some patients received surgery alone (SA, n = 131), and others received postoperative chemotherapy (POCT, n = 222), radiotherapy (PORT, n = 57), or sequential chemoradiotherapy (POCRT, n = 43). The follow-up ended on 1 Dec 2019. The 5-year overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LR) were significantly worse in the SA group (15.2%, 13.1%, and 71.6%, all p < 0.05) than in the POCT group (28.0%, 20.8%, and 66.5%), the PORT group (27.4%, 24.4%, and 46.9%), and the POCRT group (42.8%, 35.5%, and 43.0%). Furthermore, compared with the SA group, the median OS and DFS were significantly longer in the POCT, PORT, and POCRT groups (all p < 0.05). PORT and POCRT (but not POCT) also significantly reduced the LR (p < 0.01). Multivariate Cox analysis showed that each type of postoperative therapy was independently associated with improvements in OS, DFS, and LR. Postoperative adjuvant therapy—either POCT, PORT, or POCRT—significantly improved OS and DFS in patients with pN+ ESCC after R0 surgery. PORT and PORCT significantly reduced LR in these patients. [ABSTRACT FROM AUTHOR]

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Background The AT-motif binding factor 1 (ATBF1) gene is frequently altered at the genetic level in several types of cancer, but its protein expression and subcellular localization have not been well studied in human cancers, including head and neck squamous cell carcinomas (HNSCCs). Methods ATBF1 expression and localization were examined in 5 cell lines and 197 clinical specimens of HNSCC, and correlated with pathologic and clinical characteristics. Results ATBF1 was predominantly localized in the nucleus of hyperplastic squamous epithelium. Whereas nuclear ATBF1 dramatically decreased in invasive tumors ( p = .0012), cytoplasmic ATBF1 levels progressively increased from dysplasia to invasive tumors ( p < .0001), and the increase correlated with poor survival. Reduced nuclear ATBF1 level was also detected in HNSCC cell lines. Conclusions Nuclear localization of ATBF1 is frequently interrupted in HNSCC, and the interruption is significantly associated with the progression of HNSCC. The cytoplasmic ATBF1 level could be useful for predicting patient survival. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Radiotherapy acts by damaging DNA and hindering cancer cell proliferation. H2AX is phosphorylated to produce γH2AX that accumulates in a response to DNA double-strand breaks. Non-coding RNA can influence DNA damage response and enhance DNA repair, which show potential for cancer treatment. The study aimed to observe the influence of SPI1 on the radiosensitivity of lung squamous cell carcinoma (LUSC) and to investigate the mechanisms. SPI1, TPX2, and RNF2 were overexpressed in LUSC tissues and radioresistant cells comspared with adjacent tissues and parental cells, respectively. The binding between SPI1 and TPX2 or RNF2 promoter was investigated using ChIP-qPCR and dual-luciferase assays. SPI1 bound to TPX2 and RNF2 promoters and activated their transcription. SPI1 downregulation increased the radiosensitivity of LUSC cells, which was compromised by TPX2 or RNF2 overexpression. Meanwhile, SPI1 downregulation elevated the protein expression of γH2AX at the late stage of DNA damage response and suppressed DNA damage repair in LUSC cells, which were compromised by TPX2 or RNF2. These results indicate that SPI1 silencing potentiates radiosensitivity in LUSC cells by downregulating the transcription of TPX2 and RNF2, which provides a potential target for the radiotherapy in LUSC. [Display omitted] • SPI1 was highly expressed in the LUSC tissues and cells. • SPI1 downregulation increases radiosensitivity of radioresistant LUSC cells. • SPI1 affects radiosensitivity by regulating TPX2/RNF2 expression. • TPX2 and RNF2 overexpression confers radioresistance to LUSC cells. • SPI1 mediates TPX2/RNF2 regulation on DDR. [ABSTRACT FROM AUTHOR]