Analysis of RGS2 expression and prognostic significance in stage II and III colorectal cancer

The role of RGS2 (regulator of G-protein signalling 2) has been studied in several tumours. The purpose of the present study is to investigate the correlations between clinicopathological factors and patients' survival time and RGS2 expression in stage II and III CRC (colorectal cancer) patients. Real-time quantitative PCR was performed in 36 CRC tissues with recurrence and 28 without recurrence, and in three CRC-metastasis-derived cell lines (SW620, LoVo and Colo205) and 3 primary-CRC-derived ones (SW480, Caco-2 and HCT116) to examine RGS2 mRNA expression. In addition, to provide visualized evidence for RGS2 mRNA expression, random CRC samples were also performed with RT–PCR (reverse transcription–PCR). RGS2 protein was detected by immunostaining in 118 paraffin-embedded specimens, and the correlations between clinicopathological factors and survival time and RGS2 expression were analysed. We found that RGS2 mRNA was down-regulated both in CRC tissues with recurrence and metastasis-derived cell lines, and the expression level of RGS2 was unrelated to gender, age, tumour grade, or lymphovascular or perineural invasion. However, it was positively related to disease-free survival time (P<0.05). Furthermore, low RGS2 expression indicated a poorer survival rate (P<0.05, log-rank test). Multivariate analysis also showed that weak RGS2 protein expression was an independent adverse prognosticator in CRC (P<0.05). Taken together, we suggested that down-regulation of RGS2 might play an important role in CRC metastasis and predict poor prognosis in stage II and III CRC patients.

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Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

BMC Cancer ◽

10.1186/s12885-021-08070-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sara Ribeirinho-Soares ◽

Diana Pádua ◽

Ana Luísa Amaral ◽

Elvia Valentini ◽

Daniela Azevedo ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Prognostic Significance ◽

Tumor Resection ◽

Disease Free Survival ◽

Predictive Biomarkers ◽

Stage Ii ◽

Health Concern ◽

Rank Test ◽

Low Expression

Abstract Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

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High Expression of LTBP2 Contributes to Poor Prognosis in Colorectal Cancer Patients and Correlates with the Mesenchymal Colorectal Cancer Subtype

Disease Markers ◽

10.1155/2019/5231269 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Ying Huang ◽

Guihua Wang ◽

Chunmei Zhao ◽

Rong Geng ◽

Shu Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Protein Expression ◽

Mrna Expression ◽

Cell Lines ◽

Critical Role ◽

Prognostic Significance ◽

Poor Overall Survival ◽

Expression Levels ◽

Mrna And Protein Expression

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.

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Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.681406 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qi Liu ◽

Yufei Yang ◽

Xinxiang Li ◽

Sheng Zhang

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Mean Corpuscular Volume ◽

Alcohol Intake ◽

Prognostic Significance ◽

Stage Ii ◽

Rank Test ◽

Corpuscular Volume ◽

Prognostic Role ◽

Increased Risk

ObjectiveTo elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).BackgroundMCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.MethodsEligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan–Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.ResultsA total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.ConclusionsIn CRC patients without habitual alcohol intake, low (<80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.

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High-expression of LncRNA MAFG-AS1 is associated with the prognostic of patients with colorectal cancer

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.66.11.1530 ◽

2020 ◽

Vol 66 (11) ◽

pp. 1530-1535

Author(s):

Weichun Cui ◽

Yong Wang ◽

Xiangji Shen ◽

Xudong Wu ◽

Hui Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Survival Time ◽

Cox Regression ◽

Disease Free Survival ◽

High Expression ◽

Rank Test ◽

Depth Of Invasion ◽

Chi Square ◽

Potential Biomarker ◽

Chi Square Test

SUMMARY OBJECTIVE: Long noncoding RNAs (lncRNAs) have been proven to exhibit distinct functions on the convoluted processes of tumor developments. Some studies on the biological functions of lncRNA MAFG-AS1 (MAFG-AS1) in cancers revealed that they may serve as an oncogene in some kinds of tumors, including colorectal cancer (CRC). However, little is known about the role of MAFG-AS1 in the prognostic of CRC. METHODS: A public dataset was mined for the screening of dysregulated lncRNAs in CRC. Quantitative real-time reverse transcription-polymerase chain reaction(qPCR) was used to compare the levels of MAFG-AS1 between paired MAFG-AS1 specimens and normal adjacent tissues. The correlations between MAFG-AS1 and clinic pathological features in CRC were analyzed using the chi-square test. The log-rank test and Kaplan-Meier test were carried out to compare the survival time of patients with high and low expressions of MAFG-AS1. Cox regression was applied for univariate and multivariate assays to validate whether MAFG-AS1 could be an independent factor in the prognosis of CRC. RESULTS: We found that the distinct upregulation of MAFG-AS1 in various tumors was a common event. MAFG-AS1 was distinctly up-regulated in CRC specimens compared to matched non-tumor specimens (p < 0.01). High MAFG-AS1 expressions were closely associated with depth of invasion (p = 0.011) and TNM stage (p = 0.022). Survival assays revealed that patients with high expression of MAFG-AS1 have a shorter overall survival (p = 0.0030) and disease-free survival (p = 0.0002). CONCLUSIONS: MAFG-AS1 can serve as a novel potential biomarker to predict CRC patients’ survival time.

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Prognostic significance of presence of any mucinous component in curatively resected stage II and III colorectal cancer patients who received adjuvant treatments: Data from a single tertiary center.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14660 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14660-e14660

Author(s):

Faysal Dane ◽

Mehmet Akif Ozturk ◽

Perran Fulden Yumuk ◽

Muharrem Kocar ◽

Mehmet Besiroglu ◽

...

Keyword(s):

Colorectal Cancer ◽

Survival Data ◽

Cox Regression ◽

Early Stage ◽

Prognostic Significance ◽

Disease Free Survival ◽

Rank Test ◽

Cancer Center ◽

Mucinous Component ◽

Tertiary Center

e14660 Background: Mucinous adenocarcinoma colorectal cancer (CRC) is defined as presence of more than 50% mucinous component and its prognostic significance is debatable. We analyzed the prognostic importance of positivity of any mucinous component in early stage adenocarcinoma patients who were operated and received adjuvant treatments in a single tertiary cancer center. Methods: Data from charts of early stage CRC patients curatively treated between January 1998-December 2009 in our clinic was retrospectively analyzed. Cases with any degree of mucine presence in final pathology reports were noted (including mucinous adenocarcinomas). Adjuvant treatments were either 5-FU or oxaliplatin based regimens. All rectal carcinoma patients received postoperative radiotherapy. Survival analyses were made by Kaplan-Meier estimator, and independent factors of survival were tested with Cox regression test. Survival data of subgroups were compared with log-rank test. Results: 532 patients (45% female) were analyzed. Median follow-up was 36 months. Median age at diagnosis was 62 years (24-84). Fifty-four percent of patients had rectal primary (n=292). Presence of any mucinous component was found in 94 patients (17.7%). There was a close relation between mucine presence and T stage (p=0.0001) or tumor grade (p=0.0001). There was no statistical relation between presence of mucine and lymphatic invasion, vascular invasion, or perineural invasion. Five-year disease-free survival for mucine (+) and mucine (-) tumors were, 45.7% and 61.4%, respectively (p=0.031). Five -year overall survival of mucine (+) tumors was worse than mucine (-) tumors (65% vs. 74%, p=0.004). Conclusions: Presence of any mucinous component in early stage CRC appears to be an important bad prognostic feature in our patient group, which was not previously reported in the literature to our knowledge. This “context specific prognostic property” of presence of any mucinous component might serve as a stratification factor for further adjuvant CRC studies.

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Prognostic role of microRNA-34a expression in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.472 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 472-472

Author(s):

Albert Y. Lin ◽

Natalia B. Kouzminova ◽

Jonathan Pollack ◽

Gerard Nuovo

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cell Fate ◽

Cox Regression ◽

Early Stage ◽

Prognostic Significance ◽

Rank Correlation ◽

Suppressor Gene ◽

Stage Ii ◽

Rank Test

472 Background: Colorectal Cancer (CRC) is one of the leading causes of death worldwide. MicroRNA-34a (miR-34a), a tumor suppressor gene, is known to be down-regulated in CRC cell lines and recently shown to be a cell-fate determinant in early-stage dividing colon cancer stem cells. However, its prognostic significance is unclear. Methods: MiR-34a detection was performed by in situ hybridization on a CRC tissue microarray (n=127; stage I, 21 patients; II: 42; III: 33; IV: 31). Its expression was graded as negative (no signal), low (expression in 1-19% of cancer cells), moderate (20-49% of cancer cells), and strong (50-100% of cancer cells). The correlations between miR-34a expression and EGFR, osteopontin (OPN), p53, Ki67, LEF1, VEGF, COX2, MMR, stage and grade were evaluated by chi-squared test and Spearman's rank correlation coefficient. Kaplan-Meier survival analysis, log-rank test and Cox regression model were used to assess the association of miR-34a expression with recurrence-free survival (RFS) and disease specific survival (DSS). Results: MiR-34a expression had moderate positive correlation with genes associated with tissue proliferation and invasion, including Ki67 (Spearman's r=0.28, p=0.002), and weak correlation with EGFR (r=0.2, p=0.02) and LEF1 (r=0.18, p=0.039). In the subgroup of patients (n=75; stage II/III) with negative OPN expression (n=25), weak or negative miR-34a expression was associated with worse RFS (HR=4.1; 95%CI=1.1-15.9; p=0.036) and DSS (HR=10.5; 95%CI=1.2-94.5; p=0.036). Conclusions: Our results suggest that down-regulated or absent expression of miR-34a correlates with worse RFS and DSS in stage II - III CRC patients with negative OPN expression. Further investigation of miR34a in prospective randomized studies is warranted to establish its role as a prognostic factor for CRC outcome.

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Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes

Gut ◽

10.1136/gutjnl-2017-315664 ◽

2018 ◽

Vol 68 (3) ◽

pp. 465-474 ◽

Cited By ~ 18

Author(s):

David S Williams ◽

Dmitri Mouradov ◽

Robert N Jorissen ◽

Marsali R Newman ◽

Elham Amini ◽

...

Keyword(s):

Colorectal Cancer ◽

Mismatch Repair ◽

Dna Mismatch Repair ◽

Molecular Subtype ◽

Survival Rates ◽

Prognostic Significance ◽

Disease Free Survival ◽

Stage Ii ◽

Dna Mismatch ◽

Independent Cohort

ObjectiveTumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these are independent predictors of outcome. However, the prognostic significance of combined TIL/MMR classification and how this compares to the major genomic and transcriptomic subtypes remain unclear.DesignA prospective cohort of 1265 patients with stage II/III cancer was examined for TIL/MMR status and BRAF/KRAS mutations. Consensus molecular subtype (CMS) status was determined for 142 cases. Associations with 5-year disease-free survival (DFS) were evaluated and validated in an independent cohort of 602 patients.ResultsTumours were categorised into four subtypes based on TIL and MMR status: TIL-low/proficient-MMR (pMMR) (61.3% of cases), TIL-high/pMMR (14.8%), TIL-low/dMMR (8.6%) and TIL-high/dMMR (15.2%). Compared with TIL-high/dMMR tumours with the most favourable prognosis, both TIL-low/dMMR (HR=3.53; 95% CI=1.88 to 6.64; Pmultivariate<0.001) and TIL-low/pMMR tumours (HR=2.67; 95% CI=1.47 to 4.84; Pmultivariate=0.001) showed poor DFS. Outcomes of patients with TIL-low/dMMR and TIL-low/pMMR tumours were similar. TIL-high/pMMR tumours showed intermediate survival rates. These findings were validated in an independent cohort. TIL/MMR status was a more significant predictor of prognosis than National Comprehensive Cancer Network high-risk features and was a superior predictor of prognosis compared with genomic (dMMR, pMMR/BRAFwt/KRASwt, pMMR/BRAFmut/KRASwt, pMMR/BRAFwt/KRASmut) and transcriptomic (CMS 1-4) subtypes.ConclusionTIL/MMR classification identified subtypes of stage II/III colorectal cancer associated with different outcomes. Although dMMR status is generally considered a marker of good prognosis, we found this to be dependent on the presence of TILs. Prognostication based on TIL/MMR subtypes was superior compared with histopathological, genomic and transcriptomic subtypes.

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High expression of ABCG2 is associated with doxorubicin resistance of osteosarcoma

10.21203/rs.3.rs-52326/v1 ◽

2020 ◽

Author(s):

Hao Shu ◽

Bin Yuan ◽

Yao Huang ◽

Lei Wang ◽

Bing He ◽

...

Keyword(s):

Survival Time ◽

Cell Lines ◽

Chemotherapy Resistance ◽

Disease Free Survival ◽

High Expression ◽

Expression Level ◽

Rank Test ◽

Continuous Exposure ◽

Tumor Tissues ◽

U2os Cells

Abstract Objectives Previous studies showed overexpression of ABCG2 in a variety of tumor tissues, which could potentially indicate the probability of chemotherapy resistance. This study aimed to reveal the role of ABCG2 in the development of doxorubicin (DOX) resistance and the prognosis of OS. Methods 68 OS patients were included in this study. Tumor tissues were collected for each patient during surgery. DOX-resistant OS cell lines were induced by consecutive exposure of gradually increasing concentration of DOX to the parental cell lines. Lentivirus was used for the knockdown of ABCG2 in OS cells. Cells were treated with the gradient concentration of DOX and the viability was assessed by CCK8 assay. Total RNA was isolated from the tumor tissues or tumor cells, and the expression of ABCG2 was analyzed by qPCR. The relationship between ABCG2 expression and clinicopathological characteristics of the patients was analyzed using the Student’s t-test or the Chi-square test. Cumulative survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. P < 0.05 was considered statistically significant. Results DOX-resistant OS cells were successfully established through continuous exposure to DOX. 48 h after DOX exposure, the IC 50 value of DOX-resistant HOS cells and DOX-resistant U2OS were 3.5 µM and 3.25 µM, respectively. By contrast, those of the untreated HOS and U2OS cells were 1.15 µM and 0.93 µM, respectively (p < 0.01). The mRNA expression level of ABCG2 was significantly increased in DOX-resistant cell lines. The CCK-8 assay showed that the DOX-resistant HOS cells and DOX-resistant U2OS cells transfected with ShABCG2 were more sensitive to the DOX treatment than those transfected with ShCtrl. Analysis of gene expression in OS tissues showed remarkably higher expression of ABCG2 as compared with adjacent normal tissues (p < 0.01). The disease-free survival time of patients with high expression level of ABCG2 had obviously decreased survival time than the patients with low expression (p < 0.01). Conclusions ABCG2 expression level was significantly associated with the resistance to DOX and the overall survival of OS patients. ABCG2 may become a promising therapeutic target for OS patients.

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Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

Gastroenterology Research and Practice ◽

10.1155/2016/9701574 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Kazuyoshi Shiga ◽

Masayasu Hara ◽

Takaya Nagasaki ◽

Takafumi Sato ◽

Hiroki Takahashi ◽

...

Keyword(s):

Colorectal Cancer ◽

Interleukin 6 ◽

Prognostic Significance ◽

Significant Risk ◽

Disease Free Survival ◽

Stage Ii ◽

Disease Stage ◽

Healthy Controls ◽

Preoperative Serum ◽

The Mean

Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC).Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage.Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients.Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

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Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

Biomarkers in Medicine ◽

10.2217/bmm-2020-0141 ◽

2020 ◽

Vol 14 (12) ◽

pp. 1127-1137

Author(s):

Tong-Tong Zhang ◽

Yi-Qing Zhu ◽

Hong-Qing Cai ◽

Jun-Wen Zheng ◽

Jia-Jie Hao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Stage Ii ◽

Poor Prognostic Factor ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Potential Biomarker ◽

Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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