scholarly journals Association and diagnostic value of serum SPINK4 in colorectal cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6679 ◽  
Author(s):  
Mingzhi Xie ◽  
Kezhi Li ◽  
Jilin Li ◽  
Dongcheng Lu ◽  
Bangli Hu

The role of serum serine peptidase inhibitor, Kazal type 4 (SPINK4), in colorectal cancer (CRC) is largely unknown. This study aimed to explore the association and diagnostic value of serum SPINK4 in CRC. A total of 70 preoperative CRC patients, 30 postoperative CRC patients, 30 gastric cancer patients, and 30 healthy controls were enrolled. Using enzyme-linked immunosorbent assays, we found that the serum SPINK4 level was significantly increased in preoperative CRC compared with postoperative CRC patients, gastric cancer patients, and healthy controls (p < 0.05). The serum SPINK4 level was remarkably elevated in colon cancer compared with rectal cancer and was enhanced in the M1 stage compared with the M0 stage (p < 0.05). The area under the receiver operating characteristic curve of serum SPINK4 level in the diagnosis of CRC was 0.9186, with a sensitivity and specificity of 0.886 and 0.900, respectively, and a cut-off value of 2.065. There was no significant difference between high and low expression of serum SPINK4 regarding the overall survival time and disease-free survival (p > 0.05). This study demonstrated that the serum SPINK4 level increased in CRC and was associated with the location and distant metastasis of CRC. It had a high diagnostic value in CRC but was not associated with the survival of CRC patients.

Author(s):  
Yiqiu Hu ◽  
Zhihao Fang ◽  
Jiayi Mu ◽  
Yanqin Huang ◽  
Shu Zheng ◽  
...  

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.


2020 ◽  
Author(s):  
Jia-Bin Wang ◽  
You-Xin Gao ◽  
Ning-Zi Lian ◽  
Yu-Bin Ma ◽  
Ping Li ◽  
...  

Abstract Background: We previously demonstrated that CDK5RAP3 acts as a tumour suppressor in gastric cancer through negative regulation of the Wnt/β-catenin signalling pathway, but its function in chemotherapeutic responsiveness of gastric cancer has not been investigated. In this study, we aimed to examine the clinical significance of CDK5RAP3 to predict chemotherapeutic responsiveness in gastric cancer.Methods: A collection of 188 pairs of tumour tissue microarray specimens from Fujian Medical University were employed for the discovery set, and 310 tumour tissue samples of gastric cancer patients were employed for the internal validation set. Eight-five tumour tissue samples from Qinghai University Hospital were used as the external validation set 1. Transcriptomic and clinical data of 299 gastric cancer patients from TCGA were used as the external validation set 2. CDK5RAP3 expression, microsatellite instability (MSI) status, and tumour-infiltrating lymphocytes (TIL) were examined with immunohistochemistry. Clinical outcomes of patients were compared with Kaplan-Meier curves and the Cox model.Results: In a multi-centre evaluation, increased CDK5RAP3 indication of better prognosis depends mainly on MSI-L/MSS status or TILhigh. High CDK5RAP3 expression predicts sensitive therapeutic responsiveness to postoperative adjuvant chemotherapy in gastric cancer. In a stratification analysis based on CDK5RAP3 combined with TIL or MSI status, patients with CKD5RAP3low TILlow showed no significant difference in prognosis after receiving chemotherapy, whereas patients with CKD5RAP3low TILhigh, CKD5RAP3high TILlow, and CKD5RAP3high TILhigh had better responsiveness to chemotherapy. In addition, patients with CKD5RAP3high MSI-L/MSS status benefitted the most from adjuvant chemotherapy among all patients evaluated. Conclusions: CKD5RAP3 can be used as an effective marker to evaluate individualized chemotherapy regimens in gastric cancer patients dependent on their TIL and MSI status.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 181-181
Author(s):  
Chun-Xia Du ◽  
Xiao-Yan Liu ◽  
Hong-Gang Zhang ◽  
Ai-Ping Zhou

181 Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15560-e15560
Author(s):  
Ryoichi Miyamoto ◽  
Satoshi Inagawa ◽  
Naoki Sano ◽  
Sosuke Tadano ◽  
Masayoshi Yamamoto

e15560 Background: Preoperative NLR was well known as highly repeatable, cost-effective and widely available long-term postoperative prognostic marker of gastric cancer patients. However, the utility of preoperative NLR to predict short-term outcomes in gastric cancer patients remains unclear. In this study, we addressed whether the preoperative NLR is a predictive value of short-term outcome in gastric cancer patients. Methods: We retrospectively evaluated 154 consecutive gastric cancer patients. Mean NLR was calculated, and 3.5 was set as cut-off value. The patient characteristics and perioperative outcomes were respectively compared. In addition, median survival times (MSTs) were also compared. In terms of stage II/III (UICC 7th) gastric cancer patients, median disease-free survival times (MDFSTs) were compared between the two groups. Results: The patients were then divided into two groups: low-NLR group (n = 110) and high-NLR group (n = 44). Among low-NLR group and high-NLR group, significant differences were respectively observed in preoperative symptoms [56 (51%) vs. 31 (70%); p = 0.027] and perioperative outcomes including postoperative complications [3 (2.7%) vs. 5 (11.3%); p = 0.015], intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusion [0 vs. 3 (6.8%); p = 0.042]. MSTs and MDFSTs were significantly differed (812 vs. 594 days; p = 0.04, 848 vs. 475 days; p = 0.03, respectively). Conclusions: The present study indicated that preoperative NLR influenced not only long-term outcomes but also perioperative outcomes in gastric cancer patients. Preoperative NLR is also a useful predictive value of short-term outcomes in gastric cancer patients.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Taweesak Tongtawee ◽  
Wareeporn Wattanawongdon ◽  
Theeraya Simawaranon ◽  
Soraya Kaewpitoon ◽  
Sivamate Kaengpenkae ◽  
...  

Here we investigated CD44 protein expression and its polymorphisms in patients with chronic gastritis, precancerous gastric lesions, and gastric cancer; and we evaluated our result with the risk of CD44 protein expression and clinicopathological characteristics. Our results obtained by analyzing 162 gastric cancer patients, 125 chronic gastritis, and 165 precancerous gastric lesions from three study centers in Thailand showed that CD44 expression was significantly higher in patients with precancerous gastric lesions and gastric cancer while patients with chronic gastritis were negative for CD44 staining (p=0.036). We further observed the significant association of variant genotype; gastric cancer patients carrying AG or GG of CD44 rs187116 had more increased risk of CD44 expression than wild-type (WT) carriers (AG: odds ratio (OR) = 5.67; 95% CI = 1.57–7.23; p=0.024 and GG: OR = 8.32; 95% CI = 2.94–11.42; p=0.016), but no significant difference in the risk of CD44 expression due to polymorphism in patients with precancerous gastric lesions. Our results suggested that CD44 expression could be used as a marker for the prediction of gastric cancer development, particularly in patients with precancerous gastric lesions carrying AG or GG, who were selected to surveillance follow-up for gastric cancer prevention.


2015 ◽  
pp. 22-31
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Viet Nho Le ◽  
Cong Thuan Dang ◽  
Trung Nghia Van ◽  
...  

Background: HER2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to: (1) assess the amplification and the overexpression of HER2/neu using fluorescence in situ hybridization (FISH) and immunohistochemistry in gastric cancer; (2) survey the association between HER2/neu and clinicopathologic characteristics of gastric cancer. Patients and methods: one hundred and sixty gastric cancer patients were assessed HER2/neu overexpression by IHC using Ventana anti-HER-2/neu (4B5) kit and were assessed HER2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit with biopsy specimens. Results: HER2/neu protein expression rates of IHC 0, 1+, 2+ and 3+ were 70%, 10.6%, 10.6% and 8.8%, respectively. HER2/neu gene amplification was identified in gastric cancer from 21 out of 160 (13.1%) patients. The concordance between IHC and FISH was 90.0%. The HER2/neu-positive rate assessed by both techniques was 13.1%. There was a significant difference in HER2/neu-positivity between cardia gastric cancer and non-cardia gastric cancer (36.4% vs 11.4%, p = 0.040); between intestinal type and diffuse type (20.7% vs 5.9%, p = 0.010); between well, moderately differentiated and poorly differentiated gastric cancer (18.6% and 23.8% vs 5.8%, p = 0.047). Conclusion: We applied successfully FISH and IHC technique with biopsy samples in gastric cancer detecting HER2/neu positivity in order to select patients that benefit from trastuzumab in combination with chemotherapy. HER2/neu status associated with tumor location, Lauren classification and differentiated grading. Keywords: gastric cancer, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), HER-2/neu


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4142-TPS4142
Author(s):  
Minkyu Jung ◽  
Seok Yun Kang ◽  
Bong-Seog Kim ◽  
Ki Hyang Kim ◽  
Kyung Hee Lee ◽  
...  

TPS4142 Background: Complete surgical resections remains the only chance for cure in patients with gastric cancer, but approximately from 40% to 80% of patients still have recurrences and most patients ultimately die from their disease. The recent adjuvant trials in gastric cancer showed significantly improved survival in patients with adjuvant chemotherapy than those with surgery alone. However, further studies need for the effect of adjuvant chemotherapy following D2 dissected gastric cancer patients, especially in advanced gastric cancer. S-1 is an oral anticancer drug, a prodrug of fluorouracil, very effective in gastric cancer. Docetaxel is the first drug that showed survival benefits when added to the two drugs in advanced gastric cancer patients. And docetaxel is also synergistic anti-cancer effect with S-1 in advanced gastric cancer. Base on this background, the aim of this study is to detect a significant increase in 3 –year disease free survival (DFS) of adjuvant chemotherapy with docetaxel and S-1(DS) relative to those with S-1 and cisplatin (SP) in patients with stage III gastric cancer Methods: This study is an open-label, phase 3, randomized controlled trial, multicenter in South Korea. Patients with stage III (AJCC 7th edition) gastric cancer who had had curative D2 gastrectomy is randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of intravenous docetaxel (35 mg/m2 on day 1 and 8 of each cycle) plus oral S-1 (35 mg/m2 twice daily on days 1 to 14 of each cycle) for 6 months (DS) or chemotherapy of eight 3-week cycles of oral S1 plus intravenous cisplatin (60 mg/m2). After satisfying the screening criteria, patients have been randomized to the SD or SP arm in a 1:1 ratio. The randomization is stratified by institution and stage of disease (IIIA vs. IIIB vs. IIIC). The each stratum has been randomized by using the method of randomly permuted block. The primary endpoint is 3 year DFS, will analyze by intention to treat. A total of 290 patients will be enrolled, 67 patients have been treated to day, with continuing accrual. The trial is registered at ClinicalTrials.gov (NCT01283217).


2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 264-264
Author(s):  
Nana Nakamoto ◽  
Fumiaki Nakamura ◽  
Takahiro Higashi ◽  
Momoko Iwamoto ◽  
Asuka Amano ◽  
...  

264 Background: Health insurance claims data have been used extensively as a less labor-intensive method of collecting data than medical record reviews, which are the preferred source of data collection in most medical studies. Although recent reports have raised questions about its validity of use in measuring care quality, validity of using claims data may differ by health systems and should therefore be assessed by country. We aimed to test the validity of using claims data in Japan by comparing quality performance scores obtained from claims data to those derived from medical record reviews. Methods: We reviewed medical records from Apr 2013 to Apr 2014 of gastric and colorectal cancer patients who were diagnosed in 2011 from 4 cancer care hospitals in Okinawa. We calculated the proportion of patients who received adjuvant chemotherapy for gastric and colorectal cancer using claims data, and compared the results with those obtained from medical record reviews. Chart reviews were performed by certified tumor registrars. We used kappa coefficients to measure the level of agreement between claims data and medical record reviews. Results: Analysis using claims data resulted in 14 Stage II and III gastric cancer patients who had undergone surgery, with 50% receiving adjuvant chemotherapy; whereas medical record reviews resulted in 19 patients, 94.7% of whom either received or had a clinically valid rationale for not undergoing adjuvant therapy. For colorectal patients, claims data resulted in 48.5% of 68 surgical stage III colorectal patients receiving adjuvant therapy, compared to 74.4% of 78 patients using medical record reviews who either received adjuvant therapy or had a valid reason for not undergoing therapy. Agreement between claims data and chart reviews was low (kappa=0.14) for gastric cancer, but fair (kappa =0.37) for colorectal cancer. Conclusions: Our analysis showed that use of claims data may greatly underestimate quality performance measures if they are not compensated by medical record reviews. Claims data alone cannot capture a large proportion of patients who either choose not to, or has a clinically valid reason for not undergoing standard care.


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