Prognostic Factor In Colorectal Cancer Research Articles

PROGNOSTIC MARKERS IN IMMUNOHISTOCHEMICAL DIAGNOSIS OF METASTASES OF COLORECTAL PHENOTYPE CARCINOMA OF UNKNOWN PRIMARY

Most metastases of cancers of unknown primary (80% -85%) are known as having unfavourable prognostic variants due to their large extant and low susceptibility to the therapy. Studies of prognostic immunohistochemical markers will provide an opportunity to understand the biological features of the rapid dissemination of individual colorectal phenotypes. In recent decades, p53 and Ki-67, the most popular antibodies have been investigated as prognostic factors for colorectal cancer. The p53 protein is a regulatory protein that is at the crossroads of cell division and cell death. The goal of this study is to explore the expression features of prognostic immunohistochemical markers Ki-67, p53, β-catenin, AMACR (p503s), HER2-new in carcinomas of unknown primary of the colorectal phenotype compared with primary tumours of the colon, to improve diagnostic algorithms. Materials and methods. A study of biopsy material taken from 37 patients aged 28 to 81 years (mean 58.46 ± 12.28; median 58), group 1, with metastases without primary localization was carried out; the immunohistochemical investigation revealed adenocarcinomas of the colorectal phenotype CK20 + / CDX2 + / CK7; the investigation of postoperative material in 41 patients aged 27 to 76 years (mean 60.56 ± 12.81; median 64), group 2, revealed primary colon tumour. Results. Positive focal expression of p53 was found in the colorectal cancers of the proximal sections (located to the right), it is they that more often have microsatellite instability, compared to distal carcinomas. Amplification of the Her-2-new gene (expression at the level of 2+ and 3+) was found in 35% (13 of 37) of metastasis of colorectal cancers, and in almost 15% (6 of 41) of primary colon adenocarcinomas that suggests the appropriateness in applying targeted therapy.Conclusions. Nuclear translocation of β-catenin, positive “focal” expression of p53 and amplification of the Her-2-new gene are statistically significantly more common in colorectal phenotype metastases compared with primary colon adenocarcinomas (all р> 0.05).

Dystrophin Promotes Colorectal Carcinoma Metastasis and Exosome Secretion via Protein‐Protein Interaction with Rab GTPase 3C

RAB GTPases is involved in membrane trafficking (vesicle formation) and cell motility. Recently, exocytotic RABs has been noted that the exocytosis by RABs is correlated with drug resistance and immune response in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in colorectal tumorigenicity remain unknown. RAB GTPase 3C (RAB3C) has been identified as the key component for exosome formation and exocytosis. In clinical colorectal carcinoma patient cohort, high RAB3C expression maintained its independent prognostic significance for both overall survival and disease‐free survival. We further established RAB3C‐based proteomics datasets and mass spectrometry analyses and found dystrophin (DMD) is upregulated in RAB3C ectopically overexpressed colon cancer cell lines. High DMD expression levels were found correlated with poor survival in colorectal cancer patient cohorts. Moreover, Dystrophin‐complex components including dystrobrevin (DTNA) and syntrophin (SNTA1/SNTB1) also showed the same prognosis trends in colorectal cancer patients. We further found that DMD is a rare mutant event in colorectal clinical cohort by next generation sequencing analysis. Our results showed that DMD could be stabilized by RAB3C through protein‐protein interaction. Besides, our results revealed RAB3C co‐localized with dystrophin complex by immunohistochemistry staining analysis. Merged DMD with RAB3C serves as a significant independent prognostic factor in colorectal cancer and is associated with several clinical parameters. In addition, dystrophin complex decreased cell membrane integrity and altered calcium channel activity for exocytosis. In summary, our results identified DMD is a new functional binding protein for RAB3C that affected colorectal carcinogenesis. These findings suggest a new therapeutic strategy for targeting cancer‐specific protein‐protein interactions in the treatment patients with colorectal cancer.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Erratum: Molecular profiling of colorectal tumors stratified by the histological tumor-stroma ratio - Increased expression of galectin-1 in tumors with high stromal content.

[This corrects the article DOI: 10.18632/oncotarget.25845.].

Histopathological and Immunohistochemical Study of the Prognostic Significance of Cox2 and CDX2 Expression in the Available Cases of Colorectal Carcinoma

AbstractBackground: Colorectal cancer is the third most common cancer worldwide. In Egypt, the relative frequency of colorectal cancer is about 9-12% with high male predominance 3:1. Several proteins are associated with the development and progression of colorectal cancer including Cox2 and CDX2 proteins. However, it is still controversial whether Cox2 and CDX2 expression can be regarded as prognostic factors for colorectal cancer patients.Aim of Study: The purpose of this study is to detect the immunohistochemical expression of Cox2 and CDX2 in colorectal carcinoma and correlate their expression with the available clinicopathological parameters to illustrate their prognostic role.Material and Methods: Fifty cases of colorectal carcinoma in colectomy specimens were collected retrospectively. They were stained by H & E, Cox2 and CDX2 for immunohisto-chemical study. The relations between their expression and the available clinicopathological parameters were evaluated.Results: Cox2 expression in colorectal carcinoma showed statistically significant relation with depth of tumor invasion, lymph node status, distant metastasis and tumor stage. CDX2 expression showed statistically significant inverse relation with histopathological grade, depth of tumor invasion, lymph node status, distant metastasis, tumor stage and vascular invasion. There was statistically significant relation between the immunohistochemical expression of Cox2 and CDX2 in colorectal carcinoma.Conclusions: Expression of Cox2 and loss of CDX2 are usually related to poor outcome and metastasis in colorectal cancer.

Computer aided quantification of intratumoral stroma yields an independent prognosticator in rectal cancer

PurposeTumor-stroma ratio (TSR) serves as an independent prognostic factor in colorectal cancer and other solid malignancies. The recent introduction of digital pathology in routine tissue diagnostics holds opportunities for automated TSR analysis. We investigated the potential of computer-aided quantification of intratumoral stroma in rectal cancer whole-slide images.MethodsHistological slides from 129 rectal adenocarcinoma patients were analyzed by two experts who selected a suitable stroma hot-spot and visually assessed TSR. A semi-automatic method based on deep learning was trained to segment all relevant tissue types in rectal cancer histology and subsequently applied to the hot-spots provided by the experts. Patients were assigned to a ‘stroma-high’ or ‘stroma-low’ group by both TSR methods (visual and automated). This allowed for prognostic comparison between the two methods in terms of disease-specific and disease-free survival times.ResultsWith stroma-low as baseline, automated TSR was found to be prognostic independent of age, gender, pT-stage, lymph node status, tumor grade, and whether adjuvant therapy was given, both for disease-specific survival (hazard ratio = 2.48 (95% confidence interval 1.29–4.78)) and for disease-free survival (hazard ratio = 2.05 (95% confidence interval 1.11–3.78)). Visually assessed TSR did not serve as an independent prognostic factor in multivariate analysis.ConclusionsThis work shows that TSR is an independent prognosticator in rectal cancer when assessed automatically in user-provided stroma hot-spots. The deep learning-based technology presented here may be a significant aid to pathologists in routine diagnostics.

Cancer-induced spiculation on computed tomography: a significant preoperative prognostic factor for colorectal cancer.

Cancer-induced spiculation (CIS) on computed tomography, which is reticular or linear opacification of the pericolorectal fat tissues around the cancer site, is generally regarded as cancer infiltration into T3 or T4, but its clinicopathological significance is unknown. This study examines the correlation between CIS and clinicopathological findings to establish its prognostic value. The subjects of this retrospective study were 335 patients with colorectal cancer (CRC), who underwent curative surgery between January, 2010 and December, 2011, at the National Defense Medical College Hospital in Saitama Prefecture, Japan. The level of interobserver agreement in the evaluation of CIS was substantial (83%; kappa value, 0.65). The presence of CIS was specific for T3/T4 disease (positive predictive value, 88.3%), and was significantly associated with tumor size and venous invasion. The 5-year relapse-free survival rate was significantly lower in patients with CIS than in those without CIS (68.6% and 84.0%, respectively, p = 0.001). Subgroup analysis revealed remarkable prognostic differences in patients with stage III and T3 disease. Multivariate analysis revealed that CIS was a significant independent prognostic factor. CIS was a significant preoperative prognostic factor and could be useful in the selection of preoperative therapy for patients with CRC.

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?

603 Background: Lymphotoxin alpha (LTa) is a proinflammatory cytokine expressed by inflammatory cells with a role in the regulation of tumor microenvironment (TM). A putatively functional genetic polymorphism in LTA, at locus +80 (Thr26Asn, rs1041981), has been associated with altered expression of LTa. Here, we sought to evaluate whether this polymorphism associates with two main endpoints (progression-free survival (PFS) and overall survival(OS)) in colorectal cancer (CRC). Methods: This retrospective cohort study was conducted in 166 CRC patients from a single tertiary hospital. Whole blood was used to isolate genomic DNA. Genotyping of LTA + 80 C > A was performed through real time-PCR allelic discrimination using specific Taqman probes, and confirmed by sequencing. Retrospective data and long-term outcomes were reviewed. Age and gender-adjusted logistic regression analyses were undertaken. Analyses were conducted after stratification by baseline lymphocyte count (LC) (LC < 1x103/µL vs. > 1x103/µL). Kaplan-Meier curves with Log-Rank test were used. Subsequent multivariate Cox regression proportional hazards models were calculated (P for retention > 0.1). Results: Participants’ median age was 65.9 (IR, 57.5-74.3) years, the majority were males (63%), and 58% with colon cancer. At diagnosis, 45,2% were stage III and 18,1% stage IV. The median follow up time was approximately four years (IQR, 25.5-67.0 months). We found a significant association in carriers of the A-allele to have lower LC on linear trend analysis (P for trend = 0.013). Multivariate comparisons between LTA genotypes of additive model showed an independent protective effect for heterozygous compared with C-homozygous in the association with disease progression (HR = 0.5, 95 CI = 0.3-0.97, P = 0.041), only in subjects with baseline LC >1x103/µL. In this group, a significant independent protective effect for all-cause mortality was observed in A-carriers (HR = 0.4, 95 CI = 0.1-0.97, P = 0.042). Conclusions: This LTA genetic variant in subjects with baseline LC > 1x103/µL is associated with PFS and OS in CRC. The understanding of the impact of this polymorphisms on the evolution of the disease can bring us new information on TM regulation.

The relationship between tumor budding, tumor microenvironment, and survival in patients with primary operable colorectal cancer.

581 Background: Tumour budding is an independent prognostic factor in colorectal cancer and has recently been defined by the International Consensus Conference on Tumour Budding. The aim was to use the ITBCC budding evaluation method to examine relationships between tumour budding, tumour factors, tumour microenvironment, gene expression profiles and survival in patients with primary operable CRC. Methods: Hematoxylin and Eosin (H&E) stained slides of 953 CRC patients, diagnosed between 1997 and 2007 were evaluated for tumour budding according to the ITBCC-criteria. The tumour microenvironment was evaluated using tumour stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumour inflammatory cell infiltrate. Differential gene expression was assessed using TempO-Seq gene expression profiling (BioSpyder Technologies Inc., CA, USA) using the Surrogate+Tox targeted panel (2,733 genes selected for biological diversity, maximal information content, and widespread pathway coverage). Results: High budding (n = 269/ 28%) was significantly associated with TNM stage (P < 0.001), venous invasion (P < 0.001), weak KM grade (P < 0.001), high TSP (P < 0.001) and reduced cancer specific survival (CSS) (HR = 5.04; 95% confidence interval [CI], 3.50-9.51; P < 0.001) and was independent of venous invasion, KM grade, and Ki67 proliferation index. RNA expression analysis was employed using TempO-Seq to determine differential gene expression between tumours with (n = 8) and without budding (n = 18). Three genes were identified as significantly differentially expressed: S100A2 (S100 calcium binding protein A2) was upregulated by 2.9 fold (padj < 0.00001); REG1A (regenerating family member 1 alpha) was downregulated by 4.7 fold (padj < 0.01) and LCN2 (lipocalin 2) was downregulated by 2.2 fold (padj < 0.01). Conclusions: Tumour budding stratifies patients’ survival in primary operable colorectal cancer and associates with differing gene expression profiles and factors of the tumour. Therefore, the ITBCC budding evaluation method should be used to assess tumour budding as supplement the TNM staging system and can help to further subdivide colorectal cancer into new prognostic groups.

PIK3CD induces cell growth and invasion by activating AKT/GSK-3β/β-catenin signaling in colorectal cancer.

The catalytic subunit p110δ of phosphoinositide 3‐kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small‐interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of β‐catenin and T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK‐3β) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD‐mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β‐catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β‐catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK‐3β/β‐catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.

The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer.

Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage I-III CRC were utilised to assess tumour cell expression of MCT-1, MCT-2, LDH-1 and LDH-5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDH-5 associates with poor prognosis (HR 1.68 95% CI 0.99-2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCT-2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDH-5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27-5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal T-lymphocytes (p = 0.014). Similarly, cytoplasmic MCT-2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31-4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDH-5 was significantly associated with survival, increased tumour budding, and decreased stromal T-lymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCT-2 and LDH-5 may provide promising therapeutic targets for patients with stromal-rich CRC.

The usefulness of the status of extranodal tumor extension as a factor that can predict the recurrence of stage III colorectal cancer

Background: Extranodal tumor extension (ENTE) is considered a poor prognostic factor in colorectal cancer (CRC). This study aimed to investigate the risk factors for recurrence according to ENTE status in stage III CRC.Methods: We retrospectively evaluated 169 consecutive stage III CRC patients. All patients underwent a curative resection between 2005 and 2010. The presence or absence of ENTE was assessed in the resected lymph nodes.Results: ENTE was observed in 65 (38.5%). Recurrence occurred in 38 patients (22.5%) and was more frequent (p = .041) in the ENTE (+) group. Disease-free survival (p = .016) was significantly shorter in the ENTE (+) group than in the ENTE (−) group. In a univariable analysis, recurrence was associated with vascular invasion (p = .006), perforation (p = .024) in the ENTE (−) group and perforation (p = .048) in the ENTE (+) group. In a Cox’s regression test, vascular invasion (p = .014) and the higher ratio of metastatic lymph nodes/total removed lymph nodes (MLN/TLN) (0.009) in the ENTE (−) group and perforation (p = .025) in the ENTE (+) group were independent risk factors of recurrence.Conclusions: Vascular invasion and the higher ratio of MLN/TLN in ENTE (−) patients and perforation in ENTE (+) patients were independent risk factors of recurrence.

HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation

BackgroundPrevious studies have demonstrated that the expression of homeobox8 (HOXB8) is higher in colorectal cancer (CRC) tissues than in normal tissues; however, the precise role of HOXB8 in human CRC cells remains to be elucidated.MethodsWe generated lentiviral constructs to overexpress and silence HOXB8 in CRC cell lines, and examined their biological functions through MTT, wound healing, colony and transwell, expression of signal transducer and activator of transcription 3 (STAT3) and epithelial–mesenchymal transition (EMT) related factors through western-blot.ResultsHOXB8 knockdown inhibited cellular proliferation and invasion in vitro as well as carcinogenesis and metastasis in vivo. HOXB8 also induced EMT, which is characterized by the down-regulation of E-cadherin and the up-regulation of Vimentin, N-cadherin, Twist, Zeb1 and Zeb2. Moreover, HOXB8 activated STAT3, which is known to play an oncogenic role in diverse human malignancies.ConclusionsOur results indicate that HOXB8 may be an independent prognostic factor in CRC. Therefore, deserved a deeper research.

A study of morphological prognostic factors in colorectal cancer and survival analysis.

Globally, colorectal cancer (CRC) is one of the leading causes of cancer death. Many Asian countries experience an increasing incidence of CRC due to changes in diet and lifestyle. Many pathological prognostic factors other than the tumor-node-metastasis (TNM) staging reflect the biological behavior of tumor tissue and influence the treatment and survival. The aim is to evaluate: (1) Various morphological prognostic factors of colorectal cancer, (2) the correlation of the prognostic factors with survival, and (3) the prognostic factors with independent prognostic significance. Descriptive study conducted in a tertiary care center in Kerala. Five hundred and eighty-seven resected specimens of CRC received from January 1, 2007 to October 31, 2012 were studied for various morphological prognostic factors. Overall survival and disease-free survival were obtained by Kaplan Meier survival analysis. Cox regression analysis was performed to identify the predictors of survival. CRC incidence was higher in the age group 40-60 years and males were dominant. Rectum was the common site with bleeding per rectum as a common symptom. Predominant tumors had ulcerative gross configuration, size ≤5 cm and were free of transverse, radial margin involvement. Majority of tumors were well-differentiated adenocarcinoma with invasion beyond muscularis propria, without vascular, perineural invasion, and lymph node involvement and were in Stage II. The overall and disease-free 3-year survival rates were 89.1% and 88%, respectively. Among the eight significant factors in univariate analysis, tumor histology, depth of invasion, and perineural invasion were found to have independent prognostic significance in multivariate analysis. In addition to the TNM staging, other morphological prognostic factors should be given importance, while considering the patients for adjuvant therapy to improve the survival rates in CRC.

26P - Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?

26P - Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?

Tumour budding is associated with the mesenchymal colon cancer subtype and RAS/RAF mutations: a study of 1320 colorectal cancers with Consensus Molecular Subgroup (CMS) data

BackgroundTumour budding is an important prognostic factor in colorectal cancer (CRC). Molecular profiling of tumour buds suggests (partial) epithelial–mesenchymal transition and cancer stem-cell phenotype, similarly described in the “mesenchymal” Consensus Molecular Subtype 4 (CMS4), which identifies a particularly poor prognostic subgroup. Here, we determine the association of tumour budding with CMS classification, prognosis, and response to therapy.MethodsAMC-AJCCII-90 cohort (n = 76, stage II) was evaluated for peritumoural budding on H&E slides. LUMC (n = 270, stage I–IV), CAIRO (n = 504, metastatic CRC) and CAIRO2 (n = 472, metastatic CRC) cohorts were investigated for intratumoural budding using pan-cytokeratin-stained tissue microarrays. Budding was scored as count/area, then classified as <5 or ≥5 buds. For all cohorts, CMS classifications were available (gene-expression/immunohistochemistry-based classifiers).ResultsHigh (≥5) budding predicted a worse outcome in multivariate analysis in AMC-AJCCII-90 (p = 0.018), LUMC (p < 0.0001), and CAIRO (p = 0.03), and in CAIRO2 (continuous variable, p = 0.02). Tumour budding counts were higher in CMS4 compared to epithelial CMS2/3 cancers (p < 0.01, all), and associated with KRAS/BRAF mutations (p < 0.01, AMC-AJCCII-90, CAIRO, CAIRO2).ConclusionTumour budding is an adverse prognostic factor across all CRC stages and is associated with the mesenchymal CMS4 phenotype. KRAS/BRAF mutations are strongly correlated with tumour budding suggesting their involvement in the regulation of this process.

The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer-A retrospective cohort study.

PurposeTissue carcinoembryonic antigen (t‐CEA) and serum carcinoembryonic antigen (s‐CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s‐CEA and t‐CEA in CRC.MethodsA total of 517 patients from January 2006 to December 2010 with stages I‐III CRC were retrospectively examined, with 5‐year postoperative follow‐up and death as end‐points. T‐CEA expression, s‐CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan‐Meier method was used to analyze the 5‐year disease‐free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t‐CEA and s‐CEA expression.ResultsTumor differentiation and the number of positive lymph node harvests were significantly different among the t‐CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s‐CEA and t‐CEA expression had a significantly poorer prognosis than those with low s‐CEA (P = 0.021) and t‐CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t‐CEA was an independent prognostic factor in CRC (P < 0.001), but s‐CEA was not (P = 0.339). The 5‐year disease‐free survival rates among the t‐CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s‐CEA groups, this difference was observed only in stage III (P = 0.014).ConclusionThis study shows that postoperative t‐CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s‐CEA expression.

Correlation between K-ras gene mutation and clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites

Objective To analyze the correlation between K-ras gene mutation and clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites. Methods The clinical and pathological records of 69 patients who were pathologically confirmed as colorectal cancer and tested K-ras gene status at Wuxi People's Hospital Affiliated to Nanjing Medical University between May 2007 and August 2017 were adopted. The correlation between clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites and K-ras gene mutation status were retrospectively analyzed. And the patients were visited to adopt the prognosis data and perform the Kaplan-Meier survival analysis. Results The K-ras mutation rate was 50.7% (35/69), including 40.0% (12/30) in left-side colon cancer, 73.3% (11/15) in right-side colon cancer and 50.0% (12/24) in rectal cancer. The mutation rate of K-ras gene in patients ≥ 60 years old [61.5% (24/39) vs. 36.7% (11/30), χ2 = 4.197, P = 0.041] or serum CA19-9 raising up abnormally was conspicuously high [65.6% (19/29) vs. 37.5% (15/40), χ2 = 5.486, P = 0.019]. Other clinicopathological characteristics, such as gender, lesion location, histological classification, TNM stage, serum CEA expression, clinical features had no correlation with K-ras gene mutation status (all P > 0.05). And no relationship was found between prognosis and overall survival of colorectal cancer patients with different primary sites and K-ras gene mutation status (χ2 = 0.001, P = 0.997; χ2 = 0.583, P = 0.445). In general, the 5-year survival rate of left-side colon cancer patients was highest (76.9%), followed by rectal cancer (69.7%), and right-side colon cancer was lowest (31.3%). The primary site of colorectal cancer was related to the overall survival of patients (χ2 = 11.004, P = 0.004). Conclusions K-ras gene mutation in colorectal cancer is closely related to age and serum CA19-9 levels of the patients. The prognosis of left-side colon cancer is best, rectal cancer second, and right-side colon cancer poorest. Whether K-ras gene mutation is the prognostic factor of colorectal cancer is not clear. Testing the K-ras gene status and serum tumor index expression, distinguish the primary site and age group will provide the theory basis and promote the clinical targeted therapy and improve the survival of colorectal cancer patients. Key words: Intestinal neoplasms; Genes, ras; Pathology, clinical; Prognosis

Elevated urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and serum uric acid are associated with progression and are prognostic factors of colorectal cancer.

Background and purposeOxidative stress is closely related to the pathogenesis of colorectal cancer (CRC). 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is a typical bio-marker of oxidative stress. Serum uric acid (SUA) is one of the most abundant molecules with antioxidant properties in human blood. This study aimed to explore whether 8-oxodG and SUA could be prognostic factors of CRC.MethodsUrinary 8-oxodG level was analyzed using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). SUA concentration was measured using an automatic biochemistry analyzer. Seventy-three newly diagnosed Chinese CRC patients were included. According to the mean level of urinary 8-oxodG or SUA, patients were divided into high and low groups.ResultsThe level of 8-oxodG and SUA gradually elevated from stage I to stage IV in CRC patients. High 8-oxodG concentration and SUA levels were associated with worse overall survival (P=0.03). In the stage II and stage III CRC group, no statistically significant relationship was found between the urinary 8-oxodG level and overall survival or between the SUA level and overall survival. Nevertheless, when these two biomarkers were combined, there was a statistically significant association with overall survival (P=0.02).ConclusionElevated urinary 8-oxodG and SUA levels measured at the time of diagnosis were associated with the progression of CRC. Both urinary 8-oxodG and SUA might be valuable as CRC prognostic factors, and the combination of the two biomarkers might help to determine the prognoses of CRC, particularly in stage II and stage III CRC patients.

Relationships of kin17 protein expression with clinical features and prognosis of colorectal cancer

Background: To investigate the relationships of kin17 protein expression with the clinical features and prognosis of colorectal cancer (CRC). Methods: The clinicopathological data and paraffin specimens of 135 CRC patients in the First Affiliated Hospital of Nanchang University from November 2008 to November 2009 were collected. Immunohistochemistry was used to detect the kin17 protein expression in paraffin-embedded specimens, and the relationship between the kin17 protein expression and the clinicopathological features and prognosis of CRC were analyzed. Results: The kin17 protein expression was significantly higher in cancer tissue than in paracancerous tissue (49.6% vs . 14.8%, P vs . 60.6%, P vs . 100%, P vs . 52.9%, P Conclusions: The kin17 protein expression is remarkably up-regulated in CRC tissue, and its expression level is related to the depth of tumor invasion, lymph node metastasis/distant metastasis, clinical stage, histological grade, and vascular invasion. Also, kin17 protein is an independent prognostic factor for CRC.