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Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.
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Anticuerpos Monoclonales Humanizados , Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Compuestos de Platino , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Respuesta Patológica Completa , Antineoplásicos/uso terapéutico , Terapia Combinada , Compuestos de Platino/administración & dosificación , Compuestos de Platino/uso terapéutico , AncianoRESUMEN
SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.
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Biomarcadores de Tumor/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Ciclina D2/metabolismo , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Esófago/patología , Esófago/cirugía , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Persona de Mediana Edad , Estudios Retrospectivos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Effective tools evaluating the prognosis for patients with esophageal cancer undergoing surgery is lacking. The current study aimed to develop a nomogram to predict overall survival (OS) and provide evidence for adjuvant therapy for patients with esophageal carcinoma after esophagectomy. METHODS: The study retrospectively reviewed patients with pathologic T1N +/T2-4aN0-3, M0 thoracic esophageal squamous cell carcinoma after radical esophagectomy, with or without adjuvant therapy, in one institution as the training cohort (n = 2281). A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS, which were validated in an independent validation cohort (n = 1437). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate prognostic efficacy. RESULTS: In the training cohort, the median OS was 50.46 months, and the 5-year OS rate was 47.08%. Adjuvant therapy, sex, tumor location, grade, lymphovascular invasion, removed lymph nodes, and T and N categories were identified as predictive factors for OS. The nomogram showed favorable prognostic efficacy in the training and validation cohorts (5-year OS AUC: 0.685 and 0.744, respectively), which was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system. The nomogram distinguished OS rates among six risk groups, whereas AJCC could not separate the OS of 2A and 1B, 3C and 3B, or 3A and 2B. Patients with a nomogram score of 72 to 227 were predicted to achieve a 5-year OS increase of 10% or more from adjuvant therapy. CONCLUSION: The nomogram could effectively predict OS and aided decision making in adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.
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Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Esofagectomía/mortalidad , Nomogramas , Neoplasias Torácicas/mortalidad , Anciano , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Torácicas/patología , Neoplasias Torácicas/cirugíaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious malignancies in China. However, the exact mechanisms of tumor formation and progression are unclear. As late diagnosis and poor therapeutic efficacy result in lower survival rates, identifying biomarkers for early detection, prognostic evaluation, and recurrence monitoring of ESCC is necessary. Here we analyzed 10 protein expression profiles of ESCC core tissues and paired normal esophageal epithelial tissues using two-dimensional gel electrophoresis. We excised 29 protein spots with two-fold or greater differential expression between cancer and normal tissues and identified them using matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight mass spectrometry. The role of PA28ß in ESCC cell was confirmed using cell growth, colony formation and soft agar in TE-1 cells pre- and post- PA28ß transfection. Compared to their expression in the adjacent normal epithelia, 12 proteins, including transgelin (TAGLN), were upregulated in ESCC tissues; 17 proteins, including proteasome activator 28-beta subunit (PA28ß), were downregulated (p < 0.05). Western blotting and immunohistochemistry confirmed that PA28ß was significantly underexpressed in ESCC tissues. The functional assays demonstrate that PA28ß inhibited cell growth, proliferation and malignancy of TE-1 cells. Among the differentially expressed proteins, PA28ß is a potential tumor inhibitor.
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Biomarcadores de Tumor/biosíntesis , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Neoplasias/biosíntesis , Complejo de la Endopetidasa Proteasomal/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Complejo de la Endopetidasa Proteasomal/genética , ProteómicaRESUMEN
Caveolin-1 plays a very important role in the process of tumor cell transformation. In this paper, we studied the relationship between Cav-1 and other multi drug resistance associated proteins. Moreover, the author compares outcomes according to the extent of lymphadenectomy in patients with upper and middle thoracic esophageal squamous cell carcinoma without clinical cervical metastasis. The short-term and long-term data of 842 consecutive patients who underwent esophagectomy with two-field lymphadenectomy (2FL) or three-field lymphadenectomy (3FL) between February 2005 and July 2013 were retrospectively reviewed. If postoperative infection occurred, according to susceptibility test results, patients were given sensitive antibiotics. The yield of lymph nodes harvested was higher in the 3FL group than in 2FL (P=0.000). There was less blood loss (P =0.000), shorter operative time (P=0.000) less post-operative analgesia needed (P=0.000) and earlier hospital discharge (P =0.000) in 2FL than in 3FL.Overall morbidity was similar in the two groups. However, the rate of major complications was higher after 3FL versus 2FL (P=0.015). There was no 30-day mortality in 2FL and 3FL. The 5-year survival (2FL 35% vs 3FL 38%; P=0.297) and disease-free 5-year survival (2FL 26% vs 3FL 21%; P=0.106) were comparable between the two groups. In univariate analyses, extent of lymphadenectomy was not related to overall 5-year survival. Current results indicated that 2FL may be the preferred lymphadenectomy for upper and middle thoracic esophageal squamous cell carcinoma without clinical cervical metastasis.
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Caveolina 1/biosíntesis , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/mortalidad , Escisión del Ganglio Linfático/métodos , Subfamilia B de Transportador de Casetes de Unión a ATP/biosíntesis , Factores de Edad , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Resistencia a Múltiples Medicamentos , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Femenino , Humanos , Escisión del Ganglio Linfático/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Estudios Retrospectivos , Factores Sexuales , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesis , beta Catenina/biosíntesisRESUMEN
AIM OF THE STUDY: To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). MATERIAL AND METHODS: We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. RESULTS: Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. CONCLUSIONS: No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were possible prognostic factors.
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BACKGROUND: Lymph node metastasis (LNM) is most common in esophageal squamous cell carcinoma (SCC). The bi-directional spread is a key feature of LNM in patients with thoracic esophageal SCC (TE-SCC). The purpose of this study was to analyze the prognostic factors of survival in patients with TE-SCC with cervical lymph node metastasis (CLM) and validate the staging system of the current American Joint Committee on Cancer (AJCC) in a cohort of Chinese patients. METHODS: Of 1715 patients with TE-SCC who underwent radical esophagectomy plus three-field lymph node dissection at a single hospital between January 1993 and March 2007, 547 patients who had pathologically confirmed CLM (296 had surgery only and 251 had surgery + postoperative radiotherapy) were included in this study. The locations of the lymph nodes (LNs) were classified based on the guidelines of the Japanese Society for Esophageal Diseases. RESULTS: The rate of CLM was 31.9% for all patients and was 44.2%, 31.5%, and 14.4% for patients with upper, middle, and lower TE-SCC, respectively (P < 0.0001). The rates of metastasis to 101 (paraesophageal lymph nodes), 104 (supraclavicular lymph nodes), 102 (deep cervical lymph nodes) and 103 (retropharyngeal lymph nodes) areas were 89.0%, 25.6%, 3.7% and 0.5%, respectively. The 5-year overall survival (OS) rate with CLM was 27.7% (median survival, 27.5 months). The 5-year OS rates were 21.3% versus 34.2% (median survival, 21.9 months versus 35.4 months) for after surgery only versus surgery + postoperative radiotherapy, respectively (P < 0.0001 for both). Multivariate analysis showed that the independent prognostic factors for survival were sex, pT stage, pN stage, number of fields with positive LNs, and treatment modality. In surgery only group, the 5-year OS rates were 24.1%, 16.2% and 11.7%, respectively, when there was metastasis to 101 LN alone, 104 LN alone or both 101 LN and 104 LN. The 5-year OS rates were 17.7%, 22.5% and 31.7%, for patients with upper, middle and lower TE-SCC , respectively (P = 0.112). The 5-year OS rates were 43.0%, 25.5%, 10.2% in patients with 1 field (cervical LNs), 2 fields (cervical + mediastinal, and/or cervical + abdominal LNs), and 3 fields (cervical + mediastinal + abdominal LNs) positive LNs, respectively (P < 0.0001). The number of fields of positive LNs did not impact the OS according to different pN stage (all P > 0.05). CONCLUSION: Patients with TE-SCC with CLM have better prognosis, which supports the current AJCC staging system for esophageal SCC.
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Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Carcinoma de Células Escamosas/mortalidad , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Humanos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT. METHODS: 304 EPC patients underwent esophagectomy with three-field lymph node dissection had pathological lymph node metastases, but no hematogenous distant metastasis. Among them, 140 cases underwent postoperative RT alone, and 164 cases underwent postoperative CRT. The dose of irradiation was 50 Gy, and the chemotherapy regimen was taxol and cis-platinum, and a cycle was 21 days. RESULTS: The 1-, 3- and 5-year total survival rates of the whole group were 90.1%, 56.6% and 43.3%, respectively, with a median survival time of 49.7 months. The 5-year overall survival rates of the CRT and RT groups were 47.4% and 38.6%, respectively (P = 0.030), with a median survival time of 53.5 and 41.7 months, respectively (P = 0.030). The overall survival rates of the patients who underwent 1, 2, 3, 4 cycles of chemotherapy were 24.4%, 53.0%, 58.1% and 43.3%, respectively (P = 0.007). Among them, the 5-year total survival rate of patients with 2-4 cycles of chemotherapy was significantly better than that of patients who underwent one cycle of chemotherapy (P = 0.001). Univariate analysis showed that number of metastatic lymph nodes, pT stage, therapeutic regimen and number of chemotherapy cycles were significantly correlated with the prognosis of the patients (P < 0.05 for all). Multivariate analysis showed that number of metastatic lymph nodes, pT stage, and number of chemotherapy cycles were independent prognostic factors of the patients (P < 0.05 for all). Early toxic effects including neutropenia, radiation esophagitis, and gastrointestinal effects were significantly more severe in the CRT group than that in the RT group (P < 0.05), however, there were no significant differences of late toxic effects between the two groups (P > 0.05). CONCLUSION: Postoperative CRT for thoracic EPC with positive lymph nodes can improve the survival rate, with tolerable adverse effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas , Quimioradioterapia , Neoplasias Esofágicas , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Quimioradioterapia/efectos adversos , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Esofagitis/etiología , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Irradiación Linfática , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Neutropenia/etiología , Paclitaxel/administración & dosificación , Aceleradores de Partículas , Periodo Posoperatorio , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To analyze the prognostic factors of cervical lymph node metastasis (CLN) in thoracic esophageal squamous cell carcinoma (TESCC), and to probe and verify the esophageal carcinoma staging of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system. METHODS: A total of 1 715 TESCC patients underwent radical esophagectomy plus three-field lymph node dissection at Fujian Provincial Cancer Hospital between January 1993 and March 2007. 547 patients had pathological metastasis of CLN, and 296 patients received surgery only (S group) and 251 patients received postoperative radiotherapy (S+R group). The prognostic factors were analyzed and the pattern of recurrence and metastases was studied according to the esophageal carcinoma staging criteria of the 7th edition of AJCC TNM staging system. RESULTS: The metastasis rate of CLN was 31.9% for the entire group, 44.2%, 31.5% and 14.4% for the upper, middle and lower TESCC, respectively (P < 0.001). The 5-year overall survival rate of the patients with metastatic CLN was 27.7%, and the median overall survival time was 27.5 months. The 5-year survival rate was 21.3% in the S group and 34.2% in the S+R group, and the median survival time was 21.9 months in the S group and 35.4 months in the S+R group (P < 0.001). Multivariate analysis showed that gender, lesion length in X-ray, N stage, AJCC stage and treatment modality were independent prognostic factors of CLN metastasis in TESCC. Independent prognostic factors for S group included the primary tumor site, pT stage, N stage and AJCC stage, and N stage was an independent prognostic factor for the S+R group. CONCLUSIONS: TESCC with CLN metastasis have a better prognosis after surgery. It supports that cervical lymph nodes belong to regional lymph nodes classified in the 7th edition of AJCC TNM staging system.
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Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Carcinoma , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Análisis Multivariante , Cuello , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Neoplasias Primarias Secundarias , Pronóstico , Tasa de SupervivenciaRESUMEN
Immunotherapy is an effective treatment for esophageal cancer (ESCA) patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in ESCA. Our study aims to explore immune gene prognostic models and markers in ESCA as well as predictors for immunotherapy. The expression profiles of ESCA were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct an immune gene prognostic model. ESCA was grouped into three immune cell infiltration (ICI) clusters by CIBERSORT algorithm. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. An immune gene prognostic model was successfully constructed. The ICI score may be used as a predictor independent of tumor mutation burden. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in ESCA were identified and all related to the prognosis of ESCA patients. Our study established an effective immune gene prognostic model and identified markers for predicting the prognosis and immunotherapy response of ESCA patients.
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Variaciones en el Número de Copia de ADN , Neoplasias Esofágicas , Humanos , Pronóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Inmunoterapia , Biomarcadores , Biomarcadores de Tumor/genéticaRESUMEN
Background: Esophageal squamous cell cancer (ESCC) is an aggressive cancer with high incidence and mortality. It is crucial to predict prognosis of these patients individually. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic indicator in several tumors, including esophageal cancer. Besides inflammatory factors, nutritional status can impact survival of cancer patients. Albumin (Alb) concentration is an easily obtained indicator to reflect nutritional status. Methods: In this study, we retrospectively collected the data of patients with ESCC and used univariate and multivariate analysis to investigate the relationship between combination of NLR and Alb (NLR-Alb) and survival. Meanwhile, we compared clinical features among NLR-Alb cohorts. Results: Univariate analysis showed that age (P=0.013), gender (P=0.021), surgical type (P=0.031), preoperative therapy (P=0.007), NLR-Alb (P=0.001), and tumor-node-metastasis (TNM) status (P<0.001) were associated with 5-year overall survival (OS). In multivariate analysis, NLR-Alb [hazard ratio (HR) =2.53, 95% confidence interval (95% CI): 1.38-4.63, P=0.003] and TNM status (HR =4.76, 95% CI: 3.09-7.33, P<0.001) were independent predictive factors for 5-year OS. The 5-year OS rates were 83%, 62%, and 55% for NLR-Alb 1, NLR-Alb 2, and NLR-Alb 3, respectively (P=0.001). Conclusions: In summary, pre-operative NLR-Alb is a favorable and cost-effective index to predict prognosis of patients with ESCC individually.
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Objective: Esophageal cancer is an aggressive malignant tumor, with 90 percent of the patients prone to recurrence and metastasis. Although recent studies have identified some potential biomarkers, these biomarkers' clinical or pathological significance is still unclear. Therefore, it is urgent to further identify and study novel molecular changes occurring in esophageal cancer. It has positive clinical significance to identify a tumor-specific mutation in patients after surgery for an effective intervention to improve the prognosis of patients. Methods: In this study, we performed whole-exome sequencing (WES) on 33 tissue samples from six esophageal cancer patients with lymph node metastasis, compared the differences in the genomic and evolutionary maps in different tissues, and then performed pathway enrichment analysis on non-synonymous mutation genes. Finally, we sorted out the somatic mutation data of all patients to analyze the subclonality of each tumor. Results: There were significant differences in somatic mutations between the metastatic lymph nodes and primary lesions in the six patients. Clustering results of pathway enrichment analysis indicated that the metastatic lymph nodes had certain commonalities. Tumors of the cloned exploration results illustrated that five patients showed substantial heterogeneity. Conclusion: WES technology can be used to explore the differences in regional evolutionary maps, heterogeneity, and detect patients' tumor-specific mutations. In addition, an in-depth understanding of the ontogeny and phylogeny of tumor heterogeneity can help to further find new molecular changes in esophageal cancer, which can improve the prognosis of EC patients and provide a valuable reference for their diagnosis.
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The purpose of this study is to investigate the significance of RUNX3/H3K27me3 co-expression in surgically resected non-small-cell lung cancer (NSCLC) patients. Using tissue microarray (TMA), immunohistochemistry, fluorescent double immunostaining, and western blotting, 208 NSCLC and 5 benign pulmonary patients were studied of their expression of runt-related transcription factor 3 (RUNX3), trimethylated histone H3 at lysine 27 (H3K27me3), enhancer of zeste homolog 2 (EZH2), and Ki-67. Apoptotic index in cancerous tissue was evaluated via TdT-mediated dUTP-biotin nick end labeling (TUNEL). The correlation between clinicopathologic parameters and overall survival was determined by Cox regression and Kaplan-Meier survival estimates and log-rank test. GEPIA and KM plotter were used for validation of some survival analyses. As a result, together with other regular prognostic factors, RUNX3/H3K27me3 co-expression was found to be closely correlated with better prognosis in either pTNM-I or POCT-naive NSCLC patients, which might partially result from a higher cancerous apoptotic index. In conclusion, RUNX3/H3K27me3 co-expression defined some specific NSCLC population with better prognosis and longer OS and could probably be used as a biomarker in the prediction of better postoperative outcomes.
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The present study aimed to introduce a novel method of cervical esophagogastric anastomosis, so-called 'modified one-piece mechanical anastomosis' (MOMA) in McKeown esophagogastrectomy and to compare its feasibility, efficacy and safety with those of 'conventionally double-layer hand-sewn anastomosis' (CDHA). Between March 2016 and March 2018, 80 consecutive patients with thoracic esophageal squamous cell carcinoma undergoing McKeown esophagogastrectomy with a curative intent were included in the present study. Among them, 40 received MOMA and the other 40 received CDHA. Their medical records, including operation time, anastomotic time, estimated blood loss, postoperative complications within 30 days, as well as survival rate, were retrospectively reviewed, analyzed and compared. Total operation time, anastomotic time and estimated blood loss in the MOMA group were significantly decreased compared with those in the CDHA group (207.73±2.66 vs. 225.40±3.43 min; 10.95±0.44 vs. 23.03±0.47 min; 144.50±21.14 vs. 241.75±23.75 ml; all P<0.01). Anastomotic leakage was present in 1 patient in the CDHA group, but no patients in the MOMA group (P=1.000). Anastomotic stenosis was documented in 4 and 2 patients in the MOMA and CDHA group, respectively (P=0.392). The 30-day operative mortality was 0% and no significant difference was demonstrated in postoperative complications within groups (P>0.05). Furthermore, the disease-free and overall survival was compared by means of Kaplan-Meier survival estimates and log-rank tests and no statistical difference was determined (P=0.5114 and P=0.7875, respectively). McKeown esophagogastrectomy with MOMA may be a feasible, effective and reproducible alternative with relatively satisfactory postoperative outcomes for the treatment of TE-SCC, providing shorter operation and anastomosis times, and less estimated intraoperative blood loss.
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BACKGROUND: Lung cancer contributes significantly to the total of cancer-linked deaths globally, accounting for 1.3 million deaths each year. Preoperative albumin (Alb) concentration and neutrophil-to-lymphocyte ratio (NLR) may reflect chronic inflammation and be used to predict lung cancer outcomes. METHODS: The clinical records of 293 patients with non-small cell lung cancer (NSCLC) in Fujian Medical University Cancer Hospital & Fujian Cancer Hospital were reviewed retrospectively in this current study. Clinicopathologic pretreatment, including NLR, Glasgow prognostic score (GPS), and post-treatment value, such as tumor-node-metastasis (TNM) were documented. The cut-off finder application was employed to calculate the optimal threshold values. The significance of Alb concentration combined with NLR (COA-NLR) on the prediction of overall survival (OS) was explored using Kaplan-Meier analysis along with Cox proportional hazards. RESULTS: The results revealed that COA-NLR could independently assess the OS of patients with NSCLC [hazard ratio (HR) =1.952, 95% confidence interval (CI): 1.367 to 2.647, P<0.001]. Moreover, the 3-year OS rates were 87.2%, 68.5%, and 52.8% for the COA-NLR =0, COA-NLR =1, and COA-NLR =2, respectively (P<0.001). CONCLUSIONS: Preoperative COA-NLR value can effectively stratifies prognosis in NSCLC patients by classified patients into three independent groups. It can be adopted as an effective biomarker for prognosis in NSCLC patients treated with resection.
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Globally, esophageal cancer (ECA) is the seventh most common cancer and sixth most common cause of cancer-associated mortality. However, there are no reliable prognostic and predictive molecular markers for ECA; in addition, the pathogenesis of ECA is not fully elucidated. The expressions of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) of ECA and control groups were obtained from the RNA-sequencing (RNA-seq) data of our hospital, the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) datasets. Analyses of differentially expressed genes, the circRNA-miRNA-mRNA-competing endogenous RNA (ceRNA) network, and functional/pathway enrichment were conducted. The key targets in the ceRNA network that showed significant results in survival Cox regression analyses were selected. Furthermore, analyses of immune infiltration and autophagy genes related to the key targets were performed. Seven circRNAs, 22 miRNAs, and 34 mRNAs were identified as vital genes in ECA; the nuclear factor-κ-gene binding (NF-κB) and phosphatidylinositol-3 kinase/protein kinase B (PI3K-Akt) signaling were identified as the most enriched pathways. In addition, the LIM domain containing 2 (LIMD2) was an independent predictor of prognosis in ECA patients and closely associated with immunity and autophagy. Moreover, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed significant upregulation of LIMD2 expression in ECA tissues. ECA may be closely correlated with NF-κB and PI3K/Akt signaling. In addition, LIMD2 could be a potential prognostic and predictive marker of ECA.
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Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR935p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR935p and its downstream target in the occurrence and development of EC. Firstly, miRNA expression profiles associated with EC were accessed from the TCGA_ESCA dataset and analyzed. Subsequently, the expression patterns of miR935p and TGFßR2 were characterized in the human esophageal cell line, Het1A, and the human EC cell lines, TE1, Eca109 and EC9706, by RTqPCR and western blot analysis. WST1 assay, flow cytometry, Transwell assay, wound healing assay and bioinformatics analysis were used to explore their functions in EC cells. Finally, a dualluciferase reporter assay was employed to determine the targeted association between miR935p and TGFßR2. The results revealed that the expression of miR935p was markedly higher in EC cell lines compared with that in the normal cell line. The overexpression of miR935p facilitated cell proliferation, migration and invasion, and inhibited cell apoptosis. Additionally, TGFßR2 was identified as a functional target of miR935p in EC cells, as judged by a series of in vitro experiments. Furthermore, it was found that the simultaneous overexpression of miR935p and TGFßR2 almost had no effect on the biological behaviors of EC cells. On the whole, the present study demonstrates that miR935p promotes the proliferation, migration and invasion, and inhibits the apoptosis of EC cells by targeting TGFßR2.
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Células Epiteliales/metabolismo , Neoplasias Esofágicas/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Neoplásico/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Células Epiteliales/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Humanos , MicroARNs/genética , Proteínas de Neoplasias/genética , ARN Neoplásico/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta/genéticaRESUMEN
For resectable cancer patients, a method that could precisely predict the risk of postoperative recurrence would be crucial for guiding adjuvant treatment. Since T cell receptor (TCR) repertoires had been shown to be closely related to the dynamics of cancers, here we enrolled a cohort of patients to evaluate the potential of TCR repertoires in predicting the prognosis of resectable non-small cell lung cancers. Specifically, TCRß repertoires were analyzed in surgical tumor tissues and matched adjacent non-tumor tissues from 39 patients enrolled with resectable non-small cell lung cancer, through target enrichment and high-throughput sequencing. As a result, there are significant differences between the TCR repertories of tumor samples and those of matched adjacent non-tumor samples as evaluated by criteria like the number of clonotypes. In addition, TCR repertoires were significantly associated with a few clinical features, as well as somatic mutations. Finally, certain TCRß variable-joining (V-J) pairings were featured to build a logistic regression model in predicting postoperative recurrence of resectable non-small cell lung cancers with a testing area under the receiver operating characteristic curve (AUC) of around 0.9. Thus, we hypothesize that TCR repertoires could be potentially used to predict prognosis after curative surgery for non-small cell lung cancer patients.
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BACKGROUND: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear. METHODS: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics. RESULTS: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%. CONCLUSIONS: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC.
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OBJECTIVE: To investigate the incidence of lymph node metastasis (LNM) in early esophageal carcinoma and the techniques of dissection. METHODS: Standard three-field dissection was performed in patients with small superficial esophageal carcinoma detected by endoscopy from 1993 - 2007. The lymph node metastases in different regions were identified by histopathology. The survival rate of the cases was analyzed. RESULTS: A total of 149 patients with early esophageal carcinoma were identified by postoperative pathological examination. The overall lymph node metastasis (LNM) rate was 22.8%, and the degree of LNM was 2.4% in all fields. Most lymph node metastases from upper thoracic esophageal carcinoma were found in cervical and the right upper mediastinal nodes. The LNM from middle thoracic esophageal carcinoma were approximately equal in the cervical, mediastinal, and abdominal lymph nodes, and abdominal lymph node metastasis predominated in lower thoracic esophageal carcinoma. The metastatic rate of LNM adjacent to the right recurrent laryngeaal nerve was the highest (44.1%). Significant differences were shown among the rates of LNM in relation to different macroscopic pattern, depth of invasion and differentiation of tumor (P < 0.01), but not to the longitudinal length of tumor (P > 0.05). The overall 5-year survival rate was 77.9%. It was 87.0% in patients without LNM, and 47.1% in those with LNM. CONCLUSION: Lymph node metastasis in early esophageal carcinoma is in a high frequency. Patients with tumor invasion into the mucosa or lamina propria but without lymph node metastasis may undergo a local operation such as endoscopic mucosectomy and have a good prognosis. Patients with tumor invasion into the muscularis mucosae or submucosa should be treated with radical surgery with three-field lymphadenectomy, especially, to dissect the lymph nodes adjacent to the recurrent laryngeal nerve.