title: Increased MACC1 levels in tissues and blood identify colon adenoma patients at high risk.
abstract: Colorectal cancer is a preventable disease if caught at early stages. This disease is highly aggressive and has a higher incidence in African Americans. Several biomarkers and mutations of aggressive tumor behavior have been defined such as metastasis-associated in colon cancer 1 (MACC1) that was associated with metastasis in colorectal cancer patients. Here, we aim to assess colon tissue MACC1 protein and circulating MACC1 transcripts in colon preneoplastic and neoplastic African American patients.
  
  
  
  Patients' tissue samples (n = 143) have been arranged on three tissue microarrays for normal (n = 26), adenoma (n = 68) and cancer (n = 49) samples. Immunohistochemistry was used to detect MACC1 expression. Blood samples (n = 93) from normal (n = 45), hyperplastic (n = 15) and tubular adenoma (n = 33) patients were used to assess MACC1 transcripts using qRT-PCR. Distribution of continuous variables was tested between different diagnoses with Kruskal-Wallis test. Categorical variables were tested by Chi square test. We assessed the prognostic ability of IHC staining by calculating area under receiver operating characteristics curve (ROC) for adenoma and cancer separately. Differences between groups in terms of MACC1 transcript levels in plasma were calculated by using non-parametric (exact) Wilcoxon-Mann-Whitney tests. We performed all calculations with SPSS, version 21.
  
  
  
  In patient tissues, there was a statistically significant difference in MACC1 expression in normal vs. adenoma samples (p = 0.004) and normal vs. cancer samples (p < 0.001). There was however no major difference in MACC1 expression between adenoma vs. cancer cases or tubular adenomas vs tubulovillous adenomas. The area under the curve for both normal vs. adenoma and normal vs. cancer cases were 70 and 67 %, respectively. MACC1 expression was not correlated to age, gender or anatomical sample location. In patient plasma, MACC1 transcripts in adenoma patients were significantly higher than in plasma from normal patients (p = 0.014). However, the difference between normal and hyperplastic plasma MACC1 transcripts was not statistically significant.
  
  
  
  Metastasis-associated in colon cancer 1 is expressed at early stages of colorectal oncogenesis within the affected colonic tissue in this patient cohort. The plasma transcripts can be used to stratify African American patients at risk for potential malignant colonic lesions.
authors.affiliation: Department of Medicine and Cancer Center, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA. hashktorab@howard.edu.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125, Berlin, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Hermann
authors.affiliation: Department of Medicine and Cancer Center, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.affiliation: Department of Pathology, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Shokrani
authors.affiliation: Department of Pathology, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Medicine and Cancer Center, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA.
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Haidary
authors.affiliation: Department of Pathology, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA. hbrim@howard.edu.
authors.forename: Hassan
authors.initials: H
authors.lastname: Brim
authors.affiliation: Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125, Berlin, Germany. ustein@mdc-berlin.de.|German Cancer Consortium, Im Neuenheimer Feld 280, 69121, Heidelberg, Germany. ustein@mdc-berlin.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Stein
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D003710:Demography; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D046888:Tissue Array Analysis; D015534:Trans-Activators; D014157:Transcription Factors / Q000097:blood* / Q000235:genetics
chemical_list: C544162:MACC1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors
keywords: Adenoma; Colorectal cancer; MACC1; Prognosis