Independent Factor For Poor Survival Research Articles

Preoperative controlling nutritional status (CONUT) score is an independent prognostic factor in cholangiocarcinoma patients treated with hepatectomy

BackgroundNutritional status is one of the important factors determining the short- and long-term outcomes of surgery in cancer. This study aimed to assess the prognostic role of preoperative controlling nutritional status (CONUT) score in intrahepatic cholangiocarcinoma (iCCA) patients. MethodsA total of 101 iCCA patients who underwent hepatectomy between 2015 and 2018 at the Srinagarind Hospital, Khon Kaen University, were included in this retrospective study. Patients were classified according to the CONUT score. Univariate and multivariate analyses were performed to determine the correlation between clinicopathological features and overall survival. ResultsPatients were categorized into normal nutrition (n = 40 or 39.5%), mild (n = 54 or 53.5%), and moderate-severe malnutrition (n = 7). Patients with high CONUT scores had significantly shorter survival (HR 2.55, 95% CI 1.04–6.25, p = 0.04). In multivariable analysis, tumor size (HR = 2.58, p < 0.01), the growth pattern of mass forming combined with periductal (HR = 4, p < 0.01), lymph node metastasis (HR = 7.20, p < 0.01) and high CONUT score (HR = 4.71, p = 0.01) were independent factors for poor survival of iCCA patients. ConclusionThe preoperative CONUT score is a simple prognostic factor to predict the outcomes of iCCA patients undergoing hepatectomy.

Clinical Significance of SEC11A Expression in Patients With Locally Advanced Gastric Cancer.

SEC11A gene encodes the SPC18 protein, which has been implicated in tumour progression by inducing the secretion of various growth factors. We investigated the clinical significance of SEC11A expression in gastric cancer (GC) tissues in patients with locally advanced gastric cancer (LAGC) after curative resection. We estimated SEC11A expression in cancer tissues from 253 pStage II/III GC patients who underwent curative resection using quantitative polymerase chain reaction (PCR) and investigated the relationship of SEC11A expression with clinicopathological factors and survival. SEC11A expression was significantly related to serosal invasion, lymph node metastasis, lymphatic invasion, and pathological stage. The high-SEC11A expression group had a significantly lower survival rate than the low group (5-year survival 52.3% vs. 75.9%; p<0.005). Furthermore, in multivariate analysis, high-SEC11A expression was an independent factor of poor survival (hazard ratio, 2.010; 95% confidence interval=1.303-3.100; p=0.002). SEC11A expression in cancer tissue may be a useful prognostic marker in patients with LAGC after curative resection.

White bile in patients with malignant biliary obstruction is an independent factor of poor survival

Background and study aims White bile is defined as a colorless fluid occasionally found in the biliary tract of patients with bile duct obstruction. Its significance is not clearly established. Our objective was to analyze the prognostic value of white bile in a series of patients with biliary obstruction due to biliary or pancreatic cancer. Patients and methods The study was conducted on a series of consecutive patients with malignant obstructive jaundice. They all underwent endoscopic retrograde cholangiopancreatography with collection of bile and biliary stent insertion. White bile was defined as bile duct fluid with bilirubin level < 20 µmol/L. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS). Results Seventy-three patients were included (32 pancreatic cancers, 41 bile duct cancers). Thirty-nine (53.4 %) had white bile. The mean bile duct bilirubin level in this group was 4.2 ± 5.9 µmol/L vs 991 ± 1039 µmol/L in patients with colored bile (P < 0.0001). In the group of 54 patients not eligible for surgery, the multivariate analysis demonstrated an association between the presence of white bile and reduced OS (HR 2.3, 95 %CI 1.1–4.7; P = 0.02). Other factors independently associated with OS were metastatic extension (HR 2.8, 95 %CI 1.4–5.7) and serum total bilirubin (HR 1.003, 95 %CI 1.001–1.006). There was a significant inverse correlation between serum and bile duct bilirubin levels (r = –0.43, P = 0.0001). Conclusion White bile in patients with inoperable malignant biliary obstruction is an independent factor of poor survival.

Preoperative Utility of the Glasgow Prognostic Score on Outcomes of Patients with Locally Advanced Gastric Cancer.

To assess the utility of the Glasgow Prognostic Score (GPS) obtained before curative resection for predicting outcomes in patients with advanced gastric cancer (GC). This study retrospectively analyzed the outcomes of 337 consecutive patients with GC who underwent curative surgery for locally advanced gastric cancer between January 2003 and June 2014. GPS was assessed within 4days prior to surgery. The number of patients with GPS scores of 0, 1, and 2 was 302, 26, and 9, respectively. There was significantly more blood loss during surgery and more postoperative complications in the GPS 1/2 group than in the GPS 0 group. Patients in the GPS 1/2 group had significantly poorer overall survival than those in the GPS 0 group (p = 0.001). On multivariate analysis, GPS 1/2 was identified as an independent factor for poor survival (p = 0.019). GPS before curative resection might be a useful predictive factor for perioperative complications and survival in locally advanced GC.

The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma.

Background/AimsThe role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival.MethodsUsing prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017.ResultsThe median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients.ConclusionsThe serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

&lt;p&gt;Clinicopathological Characteristics and Survival of Small Cell Carcinoma of the Salivary Gland: a Population-Based Study&lt;/p&gt;

BackgroundSmall cell carcinoma (SmCC) of the salivary gland is rare, and the characteristics and survival are not well defined due to only case reports or case series being reported. The present study aimed to describe the clinicopathological characteristics and determine the factors associated with survival of this rare cancer.Materials and methodsA population-based study was carried out to investigate clinical characteristics and prognosis of SmCC of the salivary gland using prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database between 1988 and 2016.ResultsTotally, 198 patients with SmCC of the salivary gland were identified with an average age of 72.6±12.4 and a male to female ratio of 3.4:1. The lesions of most patients (167/198) were located in the parotid gland. The median overall survival (mOS) of all patients is 25.0 months. The 1-, 3-, 5- and 10-year survival rate was 65.7%, 40.9%, 33.0% and 22.7%, respectively. Surgery could prolong significantly the mOS by almost 17.0 months (28.0 months vs 11.0 months; P<0.01). Radiotherapy, as well as radiotherapy after surgery, could prolong the mOS (P<0.01 for both). Patients who received chemotherapy had significantly longer overall survival time than those without chemotherapy (28.0 months vs 20 months; P=0.04). The survival analysis demonstrated that old age (>72 years), lymph node (N3) and distant metastases were independent factors for poor survival, whereas radiotherapy was an independent factor for favorable survival.ConclusionSmall cell carcinoma of the salivary gland is a rare disease, and old age, lymph node and distant metastases, and radiotherapy were significantly associated with prognosis. In order to understand this disease more thoroughly, more cases with adequate information are required.

High ANKZF1 expression is associated with poor overall survival and recurrence-free survival in colon cancer.

Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients & methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p=0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p=0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways.

P2.01-018 Risk Factors in Patients with Pathological N1 or N2 Non-Small Cell Lung Cancer

Pathological (p) N1 or N2 non-small cell lung cancer (NSCLC) patients may experience poor prognosis despite complete resection; therefore, adjuvant chemotherapy is recommended for them. In this study, we investigated the risk factors for pN1 or N2 NSCLC. From March 2005 to December 2015, we retrospectively reviewed 93 patients with completely resected pN1 or N2 NSCLC. Patients with synchronous or metachronous multiple lung cancer, malignancies from other organs, or who received neoadjuvant chemoradiotherapy were excluded. Clinicopathological factors analyzed included: age, sex, serum carcinoembryonic antigen levels, surgical procedures, histology, size of invasive tumor, pathological N status, pleural invasion, lymphatic invasion, vascular invasion, and histological grade. Univariate and multivariate analyzes of disease-free survival and overall survival were conducted. The study group comprised 93 patients (64 men, 29 women; age range: 38–86 years; mean: 68±9.9 years). The median follow-up period was 35.1 months. The preoperative serum carcinoembryonic antigen level was elevated in 36 patients. Complete resection was performed in all patients, comprising pneumonectomy in two patients (including sleeve pneumonectomy), bilobectomy in three, and lobectomy in 87 (including lobectomy with bronchoplasty or resection adjacent organs). Adenocarcinoma, squamous cell carcinoma, and other histology were observed in 59, 22, and 12 patients, respectively. The maximum diameter of invasive diameter was >30 mm in 39 patients and ≤30 mm in 54. There were 52 patients with pN1 and 41 with pN2. Forty-four were with pleural invasion, 52 with lymphatic invasion, and 48 with vascular invasion. Multivariate analysis showed histology to be an independent factor for recurrence, whereas older age (>70 years), pleural invasion, and adjuvant chemotherapy were independent factors for poor survival. There were 24 patients with no adjuvant chemotherapy, 10 could not receive it because of poor postoperative performance status, and 3 were ineligible because of older age. The 5-year overall survival in patients with adjuvant chemotherapy was 61.8%, compared with 23.8% for those without (p =0.002). Older age, pleural invasion, and adjuvant chemotherapy were found to be independent factors for poor survival in pN1 or N2 NSCLC. Adjuvant chemotherapy is a potential consideration for pN1 or N2 patients. Surgery to maintain performance status may be useful in relation to undergoing adjuvant chemotherapy.

High stathmin1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma.

Stathmin 1 (STMN1) is a major cytosolic phosphoprotein regulating microtubule dynamics, thereby playing an important role in cancer progression and resistance to microtubule-binding anticancer agents. We assessed the prognostic significance of STMN1 expression and STMN1-associated resistance to docetaxel and radiation in esophageal squamous cell carcinoma (ESCC) patients. STMN1 expression was evaluated by immunohistochemistry in 172 surgical specimens. The association of STMN1 expression with chemoradiation resistance using docetaxel was examined by comparing expression in 15 biopsy specimens obtained before neoadjuvant therapy to histological grades of post-therapy surgically resected tumors. We also evaluated the effects of STMN1 on sensitivity to docetaxel and radiation in ESCC cell lines. High STMN1 immunoexpression was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion and venous invasion. Survival rates were significantly lower in ESCC patients with high STMN1 expression than in those with low STMN1 expression. Multivariable analysis showed that high STMN1 expression was an independent factor for poor survival. High STMN1 expression was also associated with poor response to neoadjuvant chemoradiotherapy using docetaxel. Knockdown of STMN1 expression enhanced ESCC cell line sensitivity to docetaxel and radiation. STMN1 appears critical for ESCC invasiveness and predicts an unfavorable prognosis in ESCC.

TNFAIP3 overexpression is an independent factor for poor survival in esophageal squamous cell carcinoma.

Tumor necrosis factor α induced protein3 (TNFAIP3) is a protein that is induced by TNF-mediated NF-κB activation and has a dual function in regulating NF-κB. TNFAIP3 is associated with inflammatory carcinogenesis in many cancer types. However, the clinical significance of TNFAIP3 expression and function in esophageal squamous cell carcinoma (ESCC) has not yet been reported. We examined 149ESCC tissue specimens to determine the clinical significance of TNFAIP3 by immunohistochemistry. Western blot analyses were used to detect TNFAIP3 expression in TE-1, TE-8, TE-15 and KYSE-70 ESCC cells and in Het-1A, a non-cancerous esophageal cell line. TNFAIP3 protein knockdown was conducted using small-interfering RNA to investigate its impact on cell proliferation, migration and invasion. Significant correlations between TNFAIP3 expression and differentiation (P=0.04) among clinicopathological characteristics of ESCC patients were demonstrated, and high TNFAIP3 expression was associated with poor survival (P=0.02). Moreover, multivariate analysis result showed that high TNFAIP3 expression was an independent factor for poor survival (P=0.04). In vitro analysis showed high expression of TNFAIP3 protein in TE-15 cells and low expression in Het-1A cells. Furthermore, the proliferation, migration and invasion of TE-15 cells after TNFAIP3 suppression by siRNA were significantly reduced. These findings suggest that TNFAIP3 protein may be an independent prognostic marker for poor survival, and a promising target for ESCC therapy.

Prognostic factors and scoring model for survival in advanced biliary tract cancer.

264 Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( &lt; 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P &lt; 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P &lt; 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P&lt; 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection.

REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype

REC8 meiotic recombination protein (REC8) was found to be preferentially methylated in gastric cancer (GC) using promoter methylation array. We aimed to elucidate the epigenetic alteration and biological function of REC8 in GC. REC8 was downregulated in 100% (3/3) of Epstein–Barr virus (EBV)-positive and 80% (8/10) of EBV-negative GC cell lines by promoter methylation, but the expression could be restored through demethylation treatment. Protein expression of REC8 was significantly lower in human primary gastric tumors than in adjacent non-tumor tissues. A negative correlation between methylation and mRNA expression of REC8 was observed in 223 gastric samples of The Cancer Genome Atlas study (r=−0.7018, P<0.001). The methylation level (%) of the REC8 promoter was significantly higher in EBV-positive gastric tumors than in EBV-negative gastric tumors, as shown by bisulfite genomic sequencing (77.6 (69.3–80.5) vs 51.4 (39.5–62.3), median (interquartile range); P<0.001); methylation levels in both subtypes of tumors were significantly higher than in normal stomach tissues (14.8 (4.2–24.0)) (both P<0.001). Multivariate analysis revealed that REC8 methylation was an independent factor for poor survival in GC patients (hazard ratio=1.68, P<0.05). REC8 expression significantly suppressed cell viability, clonogenicity and cell cycle progression; it induced apoptosis and inhibited migration of AGS-EBV (EBV-positive) and BGC823 (EBV-negative) GC cells, and it suppressed tumorigenicity in nude mice. In contrast, knockdown of REC8 in gastric epithelial immortalized GES-1 cells significantly increased cell viability, clonogenicity and migration ability. The tumor-suppressive effect of REC8 is mediated at least in part by the downregulation of genes involved in cell growth (G6PD, SLC2A1, NOL3, MCM2, SNAI1 and SNAI2), and the upregulation of apoptosis/migration inhibitors (GADD45G and LDHA) and tumor suppressors (PinX1, IGFBP3 and ETS2). In conclusion, REC8 is a novel tumor suppressor that is commonly downregulated by promoter methylation in GC, especially in the EBV-associated subtype. Promoter methylation of REC8 is an independent risk factor for the shortened survival of GC patients.

Low disabled-2 expression promotes tumor progression and determines poor survival and high recurrence of esophageal squamous cell carcinoma.

Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P<0.05). The Cox-regression model revealed low-DAB2 expression was an independent factor of poor survival (P<0.05), and also of tumor recurrence with the predictive performance superior to clinical TNM stage (P<0.05). Low-DAB2 cancer cells, validated by DAB2 knockdown or over-expression, had higher phosphorylated ERK and migration abilities, which could be suppressed by ERK inhibitor treatment. TGF-β-induced epithelial-to-mesenchymal transition (EMT) only existed in the high-DAB2 cells, and related to worse prognosis of high-DAB2 ESCCs (P<0.05). In conclusion, DAB2 can suppress the ERK signaling, but correlate to have TGF-β-induced EMT in ESCCs. DAB2 expression could be a biomarker to identify patients with worse survival and high recurrence. Our data suggest DAB2 expression can stratify patients in need of aggressive surveillance and with possible benefit from anti-ERK or anti-TGF-β therapies.

Heterogeneous prognosis and adjuvant chemotherapy in pathological stage I non-small cell lung cancer patients.

BackgroundEven after curative resection, the prognosis of pathological stage I non-small cell lung cancer (NSCLC) can be heterogeneous, and the use of adjuvant chemotherapy in these patients is controversial. We aimed to identify the prognostic factors and role of adjuvant chemotherapy in pathological stage I NSCLC.MethodsWe retrospectively analyzed the correlations between clinicopathological factors and survival in 179 patients with resected pathological stage I NSCLC.ResultsAfter a median follow-up of 93 months, overall and disease-free survival were not significantly different between pathological stage IA (n = 138) and IB (n = 41) patients. The prognosis of pathological stage I patients with poorly differentiated tumors was significantly worse than that of those with non-poorly differentiated tumors (P = 0.003). Multivariate analysis revealed that poor tumor differentiation was an independent factor for poor survival (hazard ratio = 6.889). A marginally significant survival benefit was observed in poorly differentiated pathological stage I patients who received adjuvant chemotherapy (P = 0.053).Pathological stage IA patients who received adjuvant chemotherapy had a worse prognosis than those who did not receive adjuvant chemotherapy (P < 0.001), whereas pathological stage IA patients with poorly differentiated tumors who received adjuvant chemotherapy had better survival than who did not receive adjuvant chemotherapy (P < 0.001).ConclusionsPoor differentiation is an independent prognostic factor in pathological stage I NSCLC after surgical resection. Adjuvant chemotherapy may be beneficial in poorly differentiated pathological stage IA NSCLC patients.

Survival Outcomes and Prognostic Factors of Surgical Therapy for All Potentially Resectable Intrahepatic Cholangiocarcinoma: a Large Single-Center Cohort Study

BackgroundSurgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. MethodsA retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. ResultsR0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9 % of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0 %, respectively, with corresponding rates of 79.1, 42.6, and 28.7 % for patients with R0 resection; 60.5, 20.1, and 13.9 % for patients with R1 resection; 20.5, 7.4, and 0 % for patients with R2 resection; and 3.8, 0, and 0 % for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. ConclusionsR0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC.

Expression of Rac-1 related to tumor depth, lymph node metastasis and patient prognosis in esophageal squamous cell carcinoma

Rac-1, which is a member of the Rho guanosine triphosphatase (GTPase) family, has been demonstrated to play an important role in cancer invasion and metastasis. In this study, we investigated the clinical and prognostic significance of Rac-1 in esophageal squamous cell carcinoma (ESCC). The protein and messenger ribonucleic acid (mRNA) levels of Rac-1 in normal esophageal epithelia cells and paired ESCC tissues were examined by Western blot and reverse transcription polymerase chain reaction. The results showed that Rac-1 was upregulated at the protein and mRNA levels in ESCC cancerous specimens compared with normal esophageal tissues. We then examined the correlation between Rac-1 expression and clinicopathological features using immunochemical analysis of 233 surgically resected ESCC. Rac-1 protein was expressed in 228 (97.85%) cancer tissues with cytoplasm staining, and there were significant correlations between Rac-1 expression and tumor location (P = 0.045), tumor stage (P = 0.020), tumor depth (P = 0.023) and lymph node metastasis (P = 0.009). The overall survival and disease-free rates of ESCC patients with high Rac-1 expression were much lower than those with low Rac-1 expression (P < 0.001; P < 0.001, respectively). Multivariate analysis showed that high Rac-1 expression and lymph node metastasis were two independent factors for poor survival (P < 0.001; P < 0.001, respectively). The results in this study indicate, for the first time, that Rac-1 is involved in the invasion and metastatic progression of ESCC and may be a potential marker for evaluating the prognosis of ESCC patients and a therapy target for ESCC.

Risk factors for both recurrence and survival in patients with pathological stage I non-small-cell lung cancer

Even after curative resection, a significant fraction of patients with stage I non-small-cell lung cancer (NSCLC) die primarily because of systemic relapse. The purpose of the present study was to investigate the risk factors for both recurrence and poor survival in patients with pathological (p-) stage I NSCLC. We retrospectively reviewed 467 consecutive patients from a single institution with completely resected p-stage I NSCLC. Patients with multiple lung tumours or malignancies from other organs and those who had undergone preoperative therapies were excluded. The correlation between clinicopathological factors and surgical outcomes, including disease-free survival (DFS) and overall survival (OS), was analysed. The clinicopathological factors examined were age, gender, smoking history, serum carcinoembryonic antigen (CEA) levels, serum cytokeratin 19 fragment levels, surgical procedure, tumour histology, p-stage, angiolymphatic invasion and differentiation grade. The 5-year DFS and OS rates of the total study population were 91.4 and 92.8%, respectively. Multivariate analysis results indicated that high serum CEA levels (>5.0 ng/ml) and p-stage IB were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels and p-stage IB were independent factors for poor survival. The risks of recurrence and death in patients with both high serum CEA levels and p-stage IB was 10.3 and 5.2 times higher than those observed in patients with both normal serum CEA levels and p-stage IA, respectively. High serum CEA levels and p-stage IB were independent factors for both recurrence and poor survival in p-stage I NSCLC patients.

Osteopontin expression is an independent factor for poor survival in oral squamous cell carcinoma: a computer‐assisted analysis on TMA sections

Osteopontin (OPN) is non-collagenous extracellular matrix protein involved in various physiological and pathological events, including tumor progression. The aim of this study was to analyze the expression of OPN in normal oral mucosa and oral squamous cell carcinoma (OSCC) and to assess its prognostic significance. The expression of OPN was immunohistochemicaly analyzed in 86 OSCC and compared with clinicopathological variable such as tumor size, nodal stage, WHO clinical stage, Ki-67 proliferation index, and patients' outcome. OPN mRNA was analyzed using quantitative real-time PCR and compared with protein OPN expression and clinical outcome in 18 OSCC samples. The expression of OPN protein was found in OSCC tumor cells (t-OPN) and various stromal cells (s-OPN). High level of t-OPN expression was associated with higher nodal stage (P=0.045), higher WHO clinical stage (P=0.033), and poor clinical outcome (P=0.022). In multivariate analysis, t-OPN emerged as an adverse independent factor for survival (P=0.049). Although correlated with t-OPN (P=0.005), s-OPN was not significantly associated with clinical parameters, including patients' outcome. Also, there was no association between OPN and clinical parameters at the mRNA level. OPN is upregulated in tumor and stromal OSCC cells. Tumor cell-derived OPN is involved in tumor progression and can independently predict the clinical outcome. Stromal-derived OPN probably has a different function compared with OPN secreted from tumor cells.

Function of carbonic anhydrase IX in glioblastoma multiforme

Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma.

Prognostic Significance of CD151 Expression in Esophageal Squamous Cell Carcinoma with Aggressive Cell Proliferation and Invasiveness

CD151 is a member of the tetraspanins and has recently been reported as a promoter of the malignant progression of cancer. The purpose of this study was to clarify the clinicopathological outcome and prognostic significance of the immunohistochemical expression of CD151 in esophageal squamous cell carcinoma (ESCC). We evaluated the significance of CD151 expression by immunohistochemistry in 138 surgically resected ESCC and the association of CD151 expression with clinicopathological features. Seventy-five (51.7%) ESCC showed a positive expression of CD151, which indicated a significant association with tumor depth (P=0.004), lymph node metastasis (P=0.002), distant metastasis (P=0.025), and lymphatic invasion (P=0.046), as well as the Ki-67 labeling index (P=0.011). The 5-year survival rate of ESCC patients with CD151-positive expression was significantly lower than with CD151-negative expression (positive, 43.1%; negative, 63.8%; P=0.003). Multivariate analysis showed that positive CD151 expression was not an independent factor for poor survival (P=0.096). CD151 expression is associated with tumor proliferation and invasiveness in ESCC.