Tenascin-C,a Prognostic Determinant of Esophageal Squamous Cell Carcinoma

Background

Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC).

Methods

In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined.

Results

Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient’s age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRβ, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRβ (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers.

Conclusion

Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target.     

A Molecular Prognostic Model Predicts Esophageal Squamous Cell Carcinoma Prognosis

Background

Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.

Methods

We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset).

Results

The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391–3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256–3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.

Conclusions

This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.     

Prognostic Factors of Primary Intraosseous Squamous Cell Carcinoma (PIOSCC): A Retrospective Review

ObjectivesTo delineate clinical and pathological features and determine the prognostic factors of primary intraosseous squamous cell carcinoma (PIOSCC).ResultsA total of 77 patients with PIOSCC were included in the study. Mean age at diagnosis was 58.8 years, (range, 37−81 years). Of the 77 patients, there were 58 men and 19 women. The most common location of disease was the mandible (71.42%), particularly the posterior mandible. The common presenting symptoms included jaw swelling (79.2%) and ulceration (42.65%). The estimated 2-year and 5-year overall survival were 68.9% and 38.8%, respectively. Univariate analysis identified the following as negative prognostic factors: histological grade, N classification, nodal status and treatment modalities. However, multivariate analysis determined positive nodal status, high histological grade and advanced N classification as the independent significant prognostic factors.ConclusionOur results demonstrate several clinical and pathological features of PIOSCC and identify important prognostic factors associated with overall survival in PIOSCC. These prognostic factors include nodal status, histological grade, N classification, and treatment modalities, all of which are important for patient counseling and may be useful for the development of new treatment approaches.     

Correlation of STAT1 with Apoptosis and Cell-Cycle Markers in Esophageal Squamous Cell Carcinoma

We recently found evidence that STAT1 in esophageal squamous carcinoma (ESCC) cells exerts tumor suppressor function, and it regulates five key regulators of apoptosis or cell-cycle progression, including Bcl-2, Bcl-xL, survivin, cyclin D1 and p21. In this study, we confirmed these findings in four ESCC cell lines. Using immunohistochemistry, we also assessed the expression of these proteins in 62 primary tumors. The expression of these markers was heterogeneous, ranging 39 to 69% of the cohort. Significant correlation was found between STAT1 and three proteins (p21, Bcl-xL and survivin), whereas only a trend was identified for cyclin D1 and Bcl-2. We then correlated the expression of these proteins with several clinicopathologic parameters including lymph node metastasis, depth of invasion, clinical stage and overall survival. Significant correlations were found between Bcl-2 and deep invasion (p = 0.033), survivin and lymph node metastasis (p = 0.006), as well as cyclin D1 and clinical stage (p = 0.014). Patients with p21-positive tumors had a significantly longer survival compared to those with p21-negative tumors (p = 0.031). To conclude, our findings support the concept that STAT1 exerts its tumor suppressor effects in ESCC via modulating the expression of key regulators of apoptosis and cell-cycle progression.     

ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.     

Clinicopathological and Prognostic Significance of Survivin Over-Expression in Patients with Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Background

The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis.

Methodology

Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed.

Principal Findings

Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients'' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45–2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96–5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14–0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC.

Conclusions

This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC.     

Prognostic Significance of the pN Classification Supplemented by Vascular Invasion for Esophageal Squamous Cell Carcinoma

Background

The biological behavior and clinical outcome of esophageal squamous cell carcinoma (ESCC) are difficult to predict.

Methodology/Principal Findings

We investigate the prognostic impact of vascular invasion to establish a risk stratification model to predict recurrence and overall survival. We retrospectively evaluated the vascular invasion of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. Those patients were assigned to a testing cohort and a validation cohort by random number generated in computer. The presence of vascular invasion was observed in 113 of 216 (52.3%) and 96 of 217 (44.2%) of ESCC in the training and validation cohorts, respectively. Further correlation analysis demonstrated that vascular invasion in ESCC was significantly correlated with more advanced pN classification and stage in both cohorts (P<0.05). Additionally, presence of vascular invasion in ESCC patients was associated closely with poor overall and recurrence-free survival as evidenced by univariate and multivariate analysis in both cohorts (P<0.05). In the subset of ESCC patients without lymph node metastasis, vascular invasion was evaluated as a prognostic predictor as well (P<0.05). More importantly, the combined prognostic model with pN classification supplemented by vascular invasion can significantly stratify the risk (low, intermediate and high) for overall survival and recurrence-free survival in both cohorts (P<0.05). The C-index to the combined model showed improved predictive ability when compared to the pN classification (0.785 vs 0.739 and 0.689 vs 0.650 for the training and validation cohorts, respectively; P<0.05).

Conclusions/Significance

The examination of vascular invasion could be used as an additional effective instrument in identifying those ESCC patients at increased risk of tumor progression. The proposed new prognostic model with the pN classification supplemented by vascular invasion might improve the ability to discriminate ESCC patients’ outcome.     

GRP78在食管鳞状细胞癌、不典型增生及正常食管鳞状上皮组织中的表达

目的：检测葡萄糖调节蛋白78（glucose—regulated proteins78,GRP78）在同一食管癌患者食管的鳞状细胞癌、不典型增生及正常鳞状上皮组织中的表达,研究GRP78与食管鳞状细胞癌发生发展的关系。方法：取90例食管鳞状细胞癌患者的病变组织,其病理切片中正常鳞状上皮组织、不典型增生组织和鳞状细胞癌组织均存在,用免疫组化的方法,检测GRP78在3种不同组织中表达的情况,分析G史P78与性别、年龄、浸润深度、分化程度、分期及淋巴结转移等参数之间的关系。结果：GRP78在食管正常鳞状上皮组织、不典型增生组织、鳞状细胞癌组织中的阳性表达率分别为7．8％、85．6％、47．8％,GRP78在正常食管组织、不典型增生组织、食管鳞癌组织3组中表达的差异有显著性意义（P〈0．01）。鳞状细胞癌组织中GRP78表达阴性者,年龄较阳性者大;GRP78表达与肿瘤分化程度、分期、淋巴结转移等有明显相关性。结论：GRP78在食管正常细胞向恶性细胞转化的过程中可能扮演了重要角色,检测GRP78的表达可能有助于对食管鳞状细胞癌的预防及早期诊断。     

GRP78 在食管鳞状细胞癌、不典型增生及正常食管鳞状上皮 组织中的表达

目的:检测葡萄糖调节蛋白78(glucose-regulated proteins 78,GRP78)在同一食管癌患者食管的鳞状细胞癌、不典型增生及正常鳞状上皮组织中的表达,研究GRP78与食管鳞状细胞癌发生发展的关系。方法:取90例食管鳞状细胞癌患者的病变组织,其病理切片中正常鳞状上皮组织、不典型增生组织和鳞状细胞癌组织均存在,用免疫组化的方法 ,检测GRP78在3种不同组织中表达的情况,分析GRP78与性别、年龄、浸润深度、分化程度、分期及淋巴结转移等参数之间的关系。结果:GRP78在食管正常鳞状上皮组织、不典型增生组织、鳞状细胞癌组织中的阳性表达率分别为7.8%、85.6%、47.8%,GRP78在正常食管组织、不典型增生组织、食管鳞癌组织3组中表达的差异有显著性意义(P<0.01)。鳞状细胞癌组织中GRP78表达阴性者,年龄较阳性者大;GRP78表达与肿瘤分化程度、分期、淋巴结转移等有明显相关性。结论:GRP78在食管正常细胞向恶性细胞转化的过程中可能扮演了重要角色,检测GRP78的表达可能有助于对食管鳞状细胞癌的预防及早期诊断。     

Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma

Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxylcytosine, which result in genomic DNA demethylation. It was reported that 5-hmC levels were decreased in a variety of cancers and could be regarded as an epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected by immunohistochemistry (IHC) in 173 esophageal squamous cell carcinoma (ESCC) tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50 pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot results showed that 5-hmC levels were significantly lower in ESCC tissues compared with corresponding adjacent non-tumor tissues (P = 0.029). TET2 and TET3 expression was also significantly decreased in tumor tissues compared with paired non-tumor tissues (TET2, P < 0.0001; TET3, P = 0.009), and the decrease in 5-hmC was significantly associated with the downregulation of TET2 expression (r = 0.405, P = 0.004). Moreover, the loss of 5-hmC in ESCC tissues was significantly associated with poor overall survival among patients with ESCC (P = 0.043); multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC tissues was an independent unfavorable prognostic indicator for patients with ESCC (HR = 1.569, P = 0.029). In conclusion, 5-hmC levels were decreased in ESCC tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable prognostic factor for patients with ESCC.     

Prognostic Value of Tumor-Infiltrating Lymphocytes for Patients With Head and Neck Squamous Cell Carcinoma

BACKGROUND: The prognostic value of tumor-infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) remains controversial. Additionally, there is no standardized approach or cutoff value for evaluating TIL levels. The aim of this study was to establish a feasible method and criterion to assess TIL levels for future clinical practice and research use and to explore the relationship between TIL levels and prognosis. PATIENTS AND METHODS: This retrospective cohort study reviewed the records and pathological sections of 202 patients with HNSCC who were surgically treated at Beijing Stomatological Hospital, Capital Medical University, from January 1998 to January 2011. The predictor variable was the TIL level. The main outcome assessment parameters were disease-free survival (DFS) and disease-specific survival (DSS). RESULT: The T stage (P = .008), smoking history (P = .042), alcohol history (P = .048), need for radiotherapy (P = .012) and microscopic extracapsular spread (ECS) (P = .012) were associated with the TIL level. A cutoff value equal to 70% could be taken as a threshold for TIL assessment, with a TIL level higher than 70% associated with a better prognosis (DFS rate: 51.9%, P = .018; DSS rate: 59.3%, P = .049). The Cox regression model showed that the TIL level was an independent prognostic factor for DFS (hazard ratio (HR): 0.786, 95% CI: 0.618-0.999, P = .049). CONCLUSION: The TIL level is closely related to the prognosis of patients with HNSCC. A threshold value of 70% is appropriate for TIL assessment, as patients with a TIL level higher than 70% show a better prognosis. Thus, the TIL level might serve as an independent predictor for HNSCC recurrence.     

A Panel of Overexpressed Proteins for Prognosis in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. In order to identify useful biomarkers for accurately classifying prognostic risks for ESCC patients, we examined the expression of six proteins by immunohistochemistry (IHC) in 590 paraffin-embedded ESCC samples. The candidate proteins include p53, EGFR, c-KIT, TIMP1 and PI3K-p110α reported to be altered in ESCC tissues as well as another important component of PI3K, PI3K-p85α. Of the six proteins tested, p53, EGFR, c-KIT, TIMP1 and PI3K-p85α were detected with high expression in 43.0%, 36.6%, 55.9%, 70.7% and 57.1% of tumors, respectively. Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426). Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001). Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621–2.696, P = 0.00000001). The data suggest that the three-protein panel of PI3K-p85α, EGFR and p53 is an important candidate biomarker for the prognosis of patients with ESCC.     

Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

Objective

Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1) in colorectal cancer (CRC) patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features.

Methods

Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS), disease-free survival (DFS) and clinicopathological features.

Results

9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26–0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24–0.59, P < 0.0001, respectively). High ALDH1 expression was highly correlated with the tumor (T) stage (T3 + T4 vs. T1 + T2; OR = 2.16, 95%CI: 1.09–4.28, P = 0.03), lymph node (N) stage (N1 + N2 vs. N0; OR = 1.8; 95%CI: 1.17–2.79, P = 0.008), and tumor differentiation (G3 vs. G1 + G2; OR = 1.88; 95%CI: 1.07–3.30, P = 0.03). However, high ALDH1 expression was not significantly correlated with the patient age (>60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63–1.94, P = 0.72).

Conclusions

High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age.     

影响口腔鳞状细胞癌患者预后的临床病理因素分析

目的：研究影响口腔鳞状细胞癌（Oral squamous cellcar cinoma,OSCC）术后患者预后的临床病理因素。方法：回顾性研究55例手术治疗的原发口腔鳞状细胞癌患者与预后相关的因素：年龄、性别、发病部位、颈部淋巴结转移情况、肿瘤细胞分化程度等。结果：平均发病年龄为57.35±12.02岁,牙龈鳞癌的复发转移率最高（45.5%）,舌部第二（44%）,颊部第三（37.5%）,唇癌预后最好（0.0%）。术前颈部淋巴结转移情况、肿瘤细胞分化程度与预后有关。肿瘤细胞的分化程度与术前淋巴结转移无显著相关性。术前有颈部淋巴结转移合并中低分化与预后差相关。结论：口腔鳞状细胞癌的预后与发病部位无显著相关性。肿瘤中低分化及术前有淋巴结转移者易出现术后复发转移。     

影响口腔鳞状细胞癌患者预后的临床病理因素分析

目的:研究影响口腔鳞状细胞癌(Oral squamous cellcar cinoma,OSCC)术后患者预后的临床病理因素。方法:回顾性研究55例手术治疗的原发口腔鳞状细胞癌患者与预后相关的因素:年龄、性别、发病部位、颈部淋巴结转移情况、肿瘤细胞分化程度等。结果:平均发病年龄为57.35±12.02岁,牙龈鳞癌的复发转移率最高(45.5%),舌部第二(44%),颊部第三(37.5%),唇癌预后最好(0.0%)。术前颈部淋巴结转移情况、肿瘤细胞分化程度与预后有关。肿瘤细胞的分化程度与术前淋巴结转移无显著相关性。术前有颈部淋巴结转移合并中低分化与预后差相关。结论:口腔鳞状细胞癌的预后与发病部位无显著相关性。肿瘤中低分化及术前有淋巴结转移者易出现术后复发转移。     

VEGF-A在食管鳞状细胞癌中的表达及临床意义

目的:探讨血管内皮生长因子A(VEGF-A)在食管鳞状细胞癌中的表达及临床意义。方法:收集2009年1月-2010年12月收治的45例食管鳞状细胞癌患者临床资料及病理标本,应用免疫组织化学法检测肿瘤组织VEGF-A表达及微淋巴管密度(MLVD),分析VEGF-A表达与食管鳞癌患者临床病理资料、MLVD及与患者生存期限的关系。结果:1有淋巴结转移的患者VEGF-A表达阳性率为66.67%,明显高于无淋巴结转移患者的38.10%(P0.05);2 VEGF-A阳性食管鳞状细胞癌患者MLVD为(8.35±2.45)明显高于阴性患者的(5.32±1.44),(P0.05);3VEGF-A阳性食管鳞状细胞癌患者3年存活率为41.67%明显低于阴性患者的61.90%(P0.05)。结论:VEGF-A表达在确定早期食管鳞状细胞癌淋巴结转移方面具有一定的应用价值,可以作为评价预后的有效指标。     

食管鳞癌与腺癌差异基因表达的对比分析

目的:研究食管鳞癌(esophageal squamous cell carcinoma,ESCC)与食管腺癌(esophageal adenocarcinoma,EAC)的基因差异表达,探讨ESCC与EAC发生发展的基因学基础。方法:选取8例ESCC和8例EAC组织抽提mRNA,应用cDNA芯片技术通过芯片杂交、生物信息学处理,找出两者间差异表达基因。结果:采用BioStarH-40芯片发现差异表达基因541条,差异表达基因占13.8%,其中表达增强309条(显著增强73条),表达降低232条(显著降低61条)。结论:ESCC与EAC基因表达比较,差异有统计学意义,这些差异可能在两类肿瘤不同的生物学行为中起重要作用。     

食管鳞癌与腺癌差异基因表达的对比分析

目的：研究食管鳞癌（esophageal squamous cell carcinoma,ESCC）与食管腺癌（esophageal adenocarcinoma,EAC）的基因差异表达,探讨ESCC与EAC发生发展的基因学基础。方法：选取8例ESCC和8例EAC组织抽提mRNA,应用cDNA芯片技术通过芯片杂交、生物信息学处理,找出两者间差异表达基因。结果：采用BioStarH-40芯片发现差异表达基因541条,差异表达基因占13．8％,其中表达增强309条（显著增强73条）,表达降低232条（显著降低61条）。结论：ESCC与EAC基因表达比较,差异有统计学意义,这些差异可能在两类肿瘤不同的生物学行为中起重要作用。     

Retrospective Analysis of Prognostic Factors in 205 Patients with Laryngeal Squamous Cell Carcinoma Who Underwent Surgical Treatment

Objectives

To investigate the most important factors affecting the prognosis of the patients with squamous cell carcinoma (SCC) of the larynx.

Methods

Based on the clinical and follow-up data, 205 patients with SCC of the larynx receiving total laryngectomy, partial laryngectomy, or CO₂ laser surgery in GuangDong General Hospital were retrospectively analyzed. A survival analysis was performed by the Kaplan-Meier method and a multivariable analysis of prognostic factors was carried out using the Cox proportional hazard model.

Results

Subtypes of carcinoma included 69.8% glottic and 30.2% supraglottic. Most patients were in N0 stage (77.6%), and 22.4% patients were in N1∼N3 stage. Over half of the patients were in T1∼T2 stage (55.1%), 20.0% in T3, and 24.9% in T4. Mean follow-up duration was 49.2 months. The survival rates 1, 2, and 3 years after the surgery were 99.0%, 91.7%, and 81.5%, respectively. The survival rate for those patients with clinical stage IV was significantly lower than for those with clinical stage I and II (p<0.001 and p = 0.013, respectively). The disease-free progression rates 1, 2, and 3 years after the surgery were 83.9%, 74.6%, and 71.2%, respectively. Futhermore, those patients with a Charlson score of 1 to 2 and ≥3 had higher risk of mortality than those with a Charlson score of 0 (hazard ratios of 1.8 and 2.41 p = 0.042 and p = 0.008). Multivariable analysis revealed that clinical stage, surgical margin, and comorbidity were significantly associated with both mortality and disease-free progression.

Conclusion

The surgical resection margin, clinical stage, and comorbidity were independent factors affecting the laryngeal cancer prognosis. The survival rates were lower for patients with advanced laryngeal cancer, positive surgical margins, or severe comorbidity, suggesting the importance of early diagnosis, early treatment, negative surgical margins, and conditions of comorbidity.     

A Novel Inflammation-Based Prognostic Score,the C-Reactive Protein/Albumin Ratio Predicts the Prognosis of Patients with Operable Esophageal Squamous Cell Carcinoma

Background

Inflammation-based prognostic scores such as the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), Glasgow prognostic score (GPS), and modified GPS (mGPS) have been reported to have prognostic value in patients with many types of cancer, including esophageal squamous cell carcinoma (ESCC). However, the role of the C-reactive protein/Albumin (CRP/Alb) ratio in ESCC has not yet been evaluated.

Methods

A total of 468 patients suffering from histologically proven ESCC were enrolled between January 2000 and July 2010. The GPS, mGPS, NLR, PLR and CRP/Alb ratios were tested together with established prognostic factors in univariate and multivariate Cox regression analyses of overall survival (OS).

Results

The optimal cutoff level for the CRP/Alb ratio was 0.50. The CRP/Alb ratio (continuous) had higher AUC values at 12 months (0.796), 24 months (0.805), and 36 months (0.815) than the NLR, GPS and mGPS. In univariate analysis, the 5-year OS rate for patients with a CRP/Alb ratio > 0.50 was 43.4%, while the rate for patients with a CRP/Alb ratio ≤ 0.50 was 17.7% (P < 0.0001). In multivariate analysis, patients with a CRP/Alb ratio > 0.50 had worse survival than patients with a CRP/Alb ratio ≤ 0.50 (HR: 2.44; 95% CI: 1.82–3.26; P < 0.0001).

Conclusion

In summary, to the best of our knowledge, this is the first study to identify the CRP/Alb ratio as a novel inflammation-based prognostic factor in a large group of ESCC patients. The prognostic value of the CRP/Alb ratio needs to be verified in prospective multicenter studies.