Upregulated Expression of C-X-C Chemokine Receptor 4 Is an Independent Prognostic Predictor for Patients with Gastric Cancer

Aberrant chemokine (C-X-C motif) receptor CXCR4 expressions in malignant tissues have been reported, but its role in gastric cancer prognosis remains unknown. Our studies were designed to investigate the expression and prognostic significance of CXCR4 in patients with gastric cancer. CXCR4 expression was retrospectively analyzed by immunohistochemistry in 97 patients with gastric adenocarcinoma from China. Results were assessed for association with clinical features and overall survival by using Kaplan-Meier analysis. Prognostic values of CXCR4 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating CXCR4 expression was determined by using receiver operating characteristic (ROC) analysis. The results show that CXCR4 predominantly localized in the cell membranes and cytoplasm. The protein level of CXCR4 was upregulation in gastric cancer tissues and upregulated expression of CXCR4 was only significantly associated with Lauren classification (P<0.001). Increased CXCR4 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients (P<0.001). Further multivariate Cox regression analysis suggested that intratumoral CXCR4 expression was an independent prognostic indicator for the disease. Applying the prognostic value of intratumoral CXCR4 density to TNM stage system showed a better prognostic value in patients with gastric cancer. In conclusion, intratumoral CXCR4 expression was recognized as an independent prognostic marker for the overall survival of patients with gastric cancer. On the basis of TNM stage, detection of CXCR4 expression will be helpful for predicting prognosis for patients with gastric cancer.     

Ephrin B2 Receptor and Microsatellite Status in Lymph Node-Positive Colon Cancer Survival

BACKGROUND: Ephrin B2 receptor (EphB2) is a target of the canonical wnt pathway implicated in colorectal carcinogenesis, and its down-regulation may be associated with adverse prognosis. We evaluated its prognostic value in resected colon cancer stratified by microsatellite status and other clinicopathologic characteristics. METHODS: We identified all cases of resected stage III colon cancer from 1995 to 2009 managed in the Capital Health district of Nova Scotia. Tissue microarrays were constructed and immunohistochemistry (IHC) for tumor EphB2 staining assigned into quartiles. Microsatellite status was evaluated by IHC for MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2). Microsatellite stable tumors were defined as both MLH1/MSH2 (+/+); tumors staining otherwise were classified with microsatellite instability (MSI-H). Primary and secondary outcomes were disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: We identified 159 cases with sufficient tissue for microarray analysis having a median follow-up of 3.47 years (range, 0.14–14). Median age was 61, 52% were male, 40% had an event, and 29% died. MSI-H was present in 18 (13%). Univariate analysis of EphB2 expression on DFS and OS showed a hazard ratio (HR) of 2.00 (P = .01) and 2.14 (P = .03), respectively. Multivariate analysis of EphB2 expression on DFS and OS showed an HR of 2.24 and 2.23, respectively, with tumor IHC ≤ 50%. CONCLUSIONS: In this cohort, decreased EphB2 expression was an independent prognostic factor for recurrence and death and may have prognostic relevance in tumors with MSI-H. However, this would require prospective validation in a larger study.     

Aberrant CCR4 Expression Is Involved in Tumor Invasion of Lymph Node-Negative Human Gastric Cancer

Cellular chemotaxis is the best-known function of chemokine receptors which are closely linked with tumor metastasis. In fact, positive expression of chemokine receptors could also be identified even in some patients without metastatic tumors, while the clinical relevance of this data has not been fully established. Our studies were designed to clarify the CCR4 expression profiles and to explore its potential role in histologically node-negative (pN0) gastric cancer (GC). Immunohistochemistry (IHC) or immunohistofluorescence (IHF) analysis was performed on specimens obtained from 108 patients with pN0 GC. We found that CCR4 was aberrantly over-expressed inpN0 GC tissues, with different expression patterns on tumor cells and being associated with T-stage (P = 0.002). The matrigel in vitro invasion assay revealed that over-expression of CCR4 in GC cell lines significantly enhanced the invasive capacity of these cells. Results from real-time RT-PCR and gelatinzymography showed a significant increase in matrix metalloproteinase (MMP)-9 production induced by the forced expression of CCR4 in GC cell lines. Our data suggest that the aberrant CCR4 expression is involved in tumor invasion of pN0 GC and, conceivably, antagonists of CCR4 might be useful candidates for controlling early events in tumor progression.     

Survival of Proper Hepatic Artery Lymph Node Metastasis in Patients with Gastric Cancer: Implications for D2 Lymphadenectomy

Background and Aims

There is a discrepancy between the American Joint Committee on Cancer (AJCC) guidelines (7^th edition) and the Japanese treatment guidelines (3^rd edition) with regard to the extent of D2 lymphadenectomy for gastric cancer. In the AJCC, hepatic artery station (No.12a) lymph node (LN) metastasis is classified as distant metastasis, whereas in the Japanese guidelines, this classified is regional metastasis. This study aimed to evaluate whether it is appropriate to reclassify No.12a LN metastasis as distant metastasis in consideration of survival outcome.

Methods

In this retrospective analysis, data from patients with gastric cancer who underwent regular D2 or greater lymphadenectomy between 1996 and 2006 were evaluated to determine any association between the clinicopathological features of hepatic artery LNs and survival prognosis.

Results

Among the 247 patients with gastric cancer who underwent No.12 LN harvest, 45 (18.2%) were positive for No.12a LN metastasis. No.12a LN metastasis was significantly associated with poor clinicopathological features, advanced tumor stage, and poor overall survival. The 5-year survival rate of patients with No.12a LN metastasis was significantly better than that of patients with distant metastasis (P < 0.05), but was similar to that of patients with LN involvement in the D2 lymphadenectomy region (P > 0.05). No.12a LN metastasis was shown to significantly influence survival outcome in univariate analysis, but was not identified as a significant independent predictor in multivariate analysis. In logistic multivariate regression analysis, T stage, N stage, and station No.3, 5, and 6 LN metastasis were independent predictors of No.12a LN involvement.

Conclusions

It is inappropriate to reclassify No.12a LN metastasis as distant metastasis. We propose that this be considered as regional metastasis and be included in the extent of D2 lymphadenectomy to improve survival outcomes in patients with gastric cancer.     

Decreased Expression of AZGP1 Is Associated with Poor Prognosis in Primary Gastric Cancer

Background

2-Zinc-glycoprotein 1 (AZGP1) is a multidisciplinary protein that participates in many important functions in the human body, including fertilization, immunoregulation and lipid mobilization. Recently, it has been shown that AZGP1 is also involved in carcinogenesis and tumor differentiation. In this study, we investigated the expression levels and prognostic value of AZGP1 in primary gastric cancers.

Methods and Results

We examined the expression of AZGP1 in 35 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. Furthermore, we analyzed AZGP1 expression in 248 patients who underwent resection procedures between 2005 and 2007 using immunohistochemistry. The relationships between the AZGP1 expression levels, the clinicopathological factors, and patient survival were investigated. AZGP1 expression was significantly reduced at both the mRNA (P = 0.023) and protein levels (P = 0.019) in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples. The immunohistochemical staining data showed that AZGP1 expression was significantly decreased in 52.8% (131/248) of gastric adenocarcinoma cases. Clinicopathological analysis showed that the reduced expression of AZGP1 was significantly correlated with tumor location (P = 0.011), histological grade (P = 0.005) and T stage (P = 0.008). Kaplan–Meier survival curves revealed that the reduced expression of AZGP1 was associated with a poor prognosis in gastric adenocarcinoma patients (P = 0.009). Multivariate Cox analysis identified AZGP1 expression was an independent prognostic factor for overall survival of gastric adenocarcinoma patients (HR = 1.681, 95% CI = 1.134–2.494, P = 0.011).

Conclusions

Our study suggests that AZGP1 might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.     

抑癌基因MTUS1在结直肠癌的表达与其淋巴结转移呈负相关

微管相关肿瘤抑制基因1(MTUS1)是一个新的肿瘤抑制基因,编码血管紧张素II AT受体结合蛋白（ATIPs）. MTUS1基因表达下调可促进肿瘤细胞增殖,但MTUS1基因表达在结直肠癌转移中的作用尚不知晓.本文以接受根治性手术、经病理检查证实的50例结直肠癌患者新鲜癌组织、癌旁组织和远癌组织为材料,探索MTUS1基因表达与结直肠癌淋巴结转移的关系. 荧光定量PCR及蛋白质免疫印迹揭示,有淋巴结转移的结直肠癌患者的癌及癌旁组织MTUS1 基因表达的mRNA及蛋白质水平明显低于无淋巴结转移的患者. MTUS1 蛋白质在淋巴结转移的结直肠癌患者的癌及癌旁组织表达下调,并进一步得到免疫组织化学的验证.实验结果提示,MTUS1的表达量与肿瘤的侵润深度有明显的负相关性.结合临床资料,推断抑癌基因MTUS1在肿瘤的发生、发展及淋巴转移中发挥重要作用.     

Piwil 2 Expression Is Correlated with Disease-Specific and Progression-Free Survival of Chemotherapy-Treated Bladder Cancer Patients

Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients.     

Survival Analysis of Patients with Interval Cancer Undergoing Gastric Cancer Screening by Endoscopy

AimsInterval cancer is a key factor that influences the effectiveness of a cancer screening program. To evaluate the impact of interval cancer on the effectiveness of endoscopic screening, the survival rates of patients with interval cancer were analyzed.MethodsWe performed gastric cancer-specific and all-causes survival analyses of patients with screen-detected cancer and patients with interval cancer in the endoscopic screening group and radiographic screening group using the Kaplan-Meier method. Since the screening interval was 1 year, interval cancer was defined as gastric cancer detected within 1 year after a negative result. A Cox proportional hazards model was used to investigate the risk factors associated with gastric cancer-specific and all-causes death.ResultsA total of 1,493 gastric cancer patients (endoscopic screening group: n = 347; radiographic screening group: n = 166; outpatient group: n = 980) were identified from the Tottori Cancer Registry from 2001 to 2008. The gastric cancer-specific survival rates were higher in the endoscopic screening group than in the radiographic screening group and the outpatients group. In the endoscopic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer and the patients with interval cancer were nearly equal (P = 0.869). In the radiographic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer was higher than that of the patients with interval cancer (P = 0.009). For gastric cancer-specific death, the hazard ratio of interval cancer in the endoscopic screening group was 0.216 for gastric cancer death (95%CI: 0.054-0.868) compared with the outpatient group.ConclusionThe survival rate and the risk of gastric cancer death among the patients with screen-detected cancer and patients with interval cancer were not significantly different in the annual endoscopic screening. These results suggest the potential of endoscopic screening in reducing mortality from gastric cancer.     

进展期胃癌的脾门淋巴结转移相关因素的研究

目的:探讨进展期胃癌脾门淋巴结(10组)转移的相关临床病理因素.方法:回顾分析了(2008-2011年)75例胃癌根治术伴10组淋巴结切除的进展期胃癌病例.分析了临床病理学因素和10组淋巴结转移的相关性.结果:本研究结果提示10组淋巴结转移的阳性率为52％.胃下部癌的转移率(20％)相对较低(P=0.000),大弯侧肿瘤的转移率高达76.2％.病灶的侵润深度及病理TNM分期与10组淋巴结阳性率密切相关,组织学类型或分化程度与10组淋巴结转移无统计学相关.病灶小于3 cm病例的10组淋巴结转移的阳性率为0％,而大于9 cm或Borrmann-Ⅳ的肿瘤患者的10组淋巴结转移的阳性率为100％.结论:10组淋巴结转移的高危因素包括:1.中上部胃癌;2.肿瘤位于胃大弯侧;3.大于3 cm; 4.侵达胃壁浆膜层.含以上高危因素的进展期胃癌根治手术中,建议常规行术中快速冰冻检查10组淋巴结是否存在转移;含2个以上高危因素的进展期胃癌建议行脾切除术,或如果技术条件具备应行保留脾的10组淋巴结清扫术以便最终获得R0切除.     

Analysis of Lymph Node Metastasis Correlation with Prognosis in Patients with T2 Gastric Cancer

Purpose

To investigate the correlated factors for lymph node metastasis and prognosis for patients with T2 gastric cancer.

Methods

A total of 442 patients with T2 gastric cancer who underwent gastrectomy from January 1996 to December 2009 were evaluated. The clinicopathological parameters were analyzed for lymph node metastasis and prognosis, including gender, age, tumor size, tumor location, histological type, depth of invasion, vascular tumor emboli, nervous invasion, resection type, and pathological stage.

Results

The rate of lymph node metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor size, and vascular tumor emboli were associated with lymph node metastasis. Logistic regression demonstrated that depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. The 5-year survival rate was 64.0%. Multivariate analysis showed that tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. Based on tumor size, there were significant differences of 5-year survival between small size tumor (<6 cm) and large size tumor (≥6 cm) according to stage IIA (P = 0.006). Based on tumor location, there were significant differences of 5-year survival among different tumor location according to stage IB. Based on resection type, there were significant differences of overall 5-year survival between curative surgery and palliative surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001).

Conclusion

Depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. Tumor size, tumor location, resection type, and pathological stage were independent prognostic factors.     

PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer.     

DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

Background

Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium–associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.

Methods and Findings

Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young female breast cancer patients with a 20-year follow-up indicated that in early-onset breast cancer, DEAR1 expression serves as an independent predictor of local recurrence-free survival and correlates significantly with strong family history of breast cancer and the triple-negative phenotype (ER⁻, PR⁻, HER-2⁻) of breast cancers with poor prognosis.

Conclusions

Our data provide compelling evidence for the genetic alteration and loss of expression of DEAR1 in breast cancer, for the functional role of DEAR1 in the dominant regulation of acinar morphogenesis in 3D culture, and for the potential utility of an immunohistochemical assay for DEAR1 expression as an independent prognostic marker for stratification of early-onset disease.     

Ratio between Negative and Positive Lymph Nodes Is Suitable for Evaluation the Prognosis of Gastric Cancer Patients with Positive Node Metastasis

Objective

To date, there is no consensus to evaluate the most appropriate category of the nodal metastasis for precise predication the prognosis of gastric cancer patients with positive node metastasis after curative surgery.

Methods

We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 299 gastric cancer patients with positive node metastasis after curative surgery for evaluation the optimal category of the nodal metastasis.

Results

With the univariate and multivariate survival analyses, the depth of primary tumor invasion was identified as the independent predicators with the OS of 299 gastric cancer patients with nodal metastasis postoperatively, as were the number of positive lymph nodes (PLNs), the number of negative lymph nodes (NLNs), and the ratio between negative and positive lymph nodes (RNPL). The RNPL was identified to be more suitable for predication the OS of gastric cancer patients with positive node metastasis than the ratio between positive and dissected lymph nodes (RPDL) by using the stratum procedure of survival analysis. Besides, we found both PLNs and NLNs were independently correlated with OS of gastric cancer patients with nodal metastasis when RNPL, instead of RPDL, was controlled in the partial correlation model.

Conclusions

RNPL, a new category of the nodal metastasis, was suitable for predication the OS of gastric cancer patients with nodal metastasis after curative resection, as were the PLNs, and NLNs.     

Preoperative Glycemic Control Status as a Significant Predictor of Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy

Background

The effect of diabetes mellitus (DM) on prostate cancer (PCa) outcome remains controversial. Thus, we investigated the association of DM history, glycemic control, and metformin use with oncologic outcomes after radical prostatectomy (RP).

Methods

We reviewed the records of 746 contemporary patients who had hemoglobin A1c (HbA1c) measured within the 6 months preceding RP. The associations between clinical variables and risk of adverse pathological features and biochemical recurrence (BCR) were tested using a multivariate logistic regression and multiple Cox-proportional hazards model, respectively. BCR was defined as prostatic specific antigen (PSA) > 0.2 ng/mL in 2 consecutive tests.

Results

There were no significant differences in the rates of adverse pathologic features and BCR-free survival between patients with (n = 209) and without (n = 537) a history of DM diagnosis (all p > 0.05). In multivariate analyses, high HbA1c level (≥ 6.5%) was significantly related with high pathologic Gleason score (≥ 4+3; odds ratio [OR] 1.704, p = 0.019) and BCR-free survival (OR 1.853, p = 0.007). Metformin use was not associated with BCR-free survival (OR 0.662, p = 0.125).

Conclusions

Poor glycemic control was significantly associated with BCR after RP. Meanwhile, metformin use was not associated with biochemical outcome after RP. Further investigation would be needed to identify exact mechanism underlying the impact of glycemic control on PCa treatment outcome.     

HMGB1在胃癌组织及细胞系中表达的研究

目的:近年来的研究表明,高迁移率族蛋白(1HMGB1)在肿瘤的发生及恶性演变过程中发挥重要作用,本研究旨在探讨HMGB1在胃癌组织、正常组织、胃癌细胞系SGC-7901、BGC-823、HGC-27、AGS及正常胃黏膜细胞系GES中表达情况。方法:免疫组织化学法检测HMGB1在32例可手术切除的胃癌患者组织标本(包括癌组织和正常组织)的表达情况;RT-PCR及Westren Blot检测HMGB1在胃癌细胞系SGC-7901、BGC-823、HGC-27、AGS及正常胃粘膜细胞系GES的m RNA及蛋白质表达。结果:胃癌组织HMGB1免疫组织化学染色评分高于正常组织(P0.05);RT-PCR结果显示SGC-7901、BGC-823、HGC-27、AGS、GES细胞系HMGB1 m RNA表达丰度均较高;Westren Blot检测发现胃癌细胞系SGC-7901、BGC-823、HGC-27中HMGB1蛋白水平显著高于胃癌细胞系AGS及正常胃粘膜细胞系GES。结论:HMGB1在胃癌组织及正常组织中的表达具有显著性差异。胃癌细胞系SGC-7901、BGC-823、HGC-27相对于其它胃细胞系存在HMGB1高表达,适合后续基因敲除分析工作。     

Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

Background

The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.

Methodology/Principal Findings

Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7^th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.

Conclusions/Significance

The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.     

淋巴结转移率对胃癌预后价值的评价

目的:评价淋巴结转移率(MLR)对胃癌术后患者预后的预测价值。方法:回顾性分析2004年至2006年间在我院就诊,临床资料完整的363例胃癌术后患者。按照第七版UICC/TNM(pN分期)及淋巴结转移率两种方法对淋巴结进行分期,比较两种方法评价胃癌预后的准确性及适用性,确定MLR分期方法的特点及优势。结果:363例胃癌术后患者按单变量生存分析方法将淋巴结转移率(MLR)分为四期:MLR0(0.0%)、MLR1(0-30%)、MLR2(30-70%)、MLR3(≥70%),其5年生存率分别为84.9%、58.3%、28.7%、12.9%,有显著性统计学差异(P<0.001)。pN分期分为pN0、pN1、pN2、pN3a、pN3b,其5年生存率分别为84.9%、60.8%、32.0%、21.9%、6.8%,有显著性统计学差异(P<0.001)。单因素COX生存分析后显示,MLR分期越高,预后越差(HR:MLR1,MLR2,MLR3/MLR0=1.589,4.455,9.900,P<0.001)。按清除淋巴结个数将所有病例分成两组:group1(≤15个)、group2(>15个),在该两组中比较pN及MLR分期的预后,结果显示pN3a在group1组中的5年生存率明显低于group2组(6.2%vs.38.4%,P<0.001),而MLR分期与清除淋巴结个数无统计学生存相关差异(P>0.05)。COX比例风险模型多因素分析表明,pN分期、MLR分期、肿瘤浸润深度、肿瘤分化程度均为影响预后的独立因素,以pN及MLR分期风险比最高。结论:MLR分期是评价胃癌术后患者预后的独立因素,该方法不受淋巴结清扫个数的影响,与pN分期方法相比,实用、准确、简单,可以降低pN分期因淋巴结清扫不足造成的期别转移现象。     

检测pT_(1-4a)N_(1-3)M_0期胃癌淋巴结微转移检测的临床意义

目的:探讨胃癌淋巴结微转移及临床病理因素对p T1-4aN1-3M0期胃癌患者术后5年无瘤生存率的影响。方法:选取我院2009年1月至12月期间胃肠外科单一手术组行D2胃癌根治术p T1-4aN1-3M0期患者63例1427枚HE染色阴性淋巴结,应用免疫组化法检测这些淋巴结中CK19表达,观察微转移的情况并分析发生微转移的胃癌患者临床病理特征及对患者5年无瘤生存率的影响。结果:临床病理分期p T1-4aN1-3M0胃癌患者中,经免疫组化染色,1427枚HE常规染色阴性淋巴结中CK19阳性表达率为15.49%(221/1427);63例胃癌患者中CK19表达阳性率39.68%(25/63);术后随访时间5.6~68.5月(平均时间43.88月),淋巴结中CK19阴性表达、阳性表达患者的总5年生存率分别为52.63%、28.00%;两者无瘤生存率差异有统计学意义(x2=8.677,P=0.003)。淋巴结CK19阳性表达与胃癌患者的肿瘤直径(P0.05)、浸润胃壁深度(P0.05)有关。COX生存回归分析显示淋巴结微转移为独立预后因素。25例患者发现淋巴结微转移并推荐再分期,再分期率39.68%(25/63)。结论:p T1-4aN1-3M0期胃癌病人,CK-19免疫组化法染色能检出常规HE染色阴性淋巴结中的微转移,有助于细化分期、判断预后及指导治疗。