MPM grade may be used as a simple and convenient marker of sarcopenia and to identify patients at increased risk of complications after colorectal cancer surgery.
We identified a novel prognostic biomarker for the distant metastasis of colorectal cancer (CRC) using comprehensive combined copy number and gene expression analyses. Expression of mRNA in CRC tissue was profiled in 115 patients using an Affymetrix Gene Chip, and copy number profiles were generated for 122 patients using an Affymetrix 250K Sty array. Genes showing both upregulated expression and copy number gains in cases involving distant CRC metastasis were extracted as candidate biomarkers. Expression of the candidate gene mRNA was validated in 86 patients using quantitative reverse transcription polymerase chain reaction assays. Expression of the protein encoded by the candidate gene was assessed using immunohistochemical staining of tissue from 269 patients. The relationship between protein expression and clinicopathologic features was also examined. Following combined copy number and gene expression analyses, three genes linked to distant metastasis of CRC were extracted as candidate biomarkers. The expression of NUCKS1, reportedly overexpressed in several cancers other than CRC, was significantly higher in CRC tissue than in normal tissue. Overexpression of the NUCKS1 protein in CRC cells was found to be associated with significantly worse overall survival and relapse-free survival, indicating that NUCKS1 is an independent risk factor for CRC recurrence. The overexpression of NUCKS1 in cancer cells could be used as a CRC prognostic marker and might also be a target for treatment of this disease.Colorectal cancer (CRC) is now the third most prevalent cancer and the second leading cause of cancer-related mortality worldwide. 1 In Japan, the incidence of CRC has doubled over the past 20 years such that CRC is now the second most deadly neoplastic disease. 2,3 Surgery is still the most effective treatment for CRC. Among those patients that undergo curative surgery, some develop local recurrence or distant metastases that lead to shorter survival times. 4 Distant metastasis has a critical influence on the prognosis of CRC. Clinicopathologic indicators such as the tumor node metastasis (TNM) classification system of the International Union Against Cancer (UICC) remain the standard for prognosis and provide the basis for therapeutic decision making. However, clinicopathologic indicators alone do not enable clinicians to make precise prognoses for individual CRC patients. 5 In order to develop personalized therapy regimens, it is therefore critical that researchers identify novel genes involved in distant metastasis that can serve as predictive biomarkers. 6 A particularly powerful tool for identifying potential biomarker genes for use in cancer prognosis is the microarray. 7-9 It is now possible with microarray analysis to investigate several thousand cancer-related or cancer-specific genes at once.Chromosomal structural alterations play an important role in cancer development. In CRC, copy number aberrations (CNAs), including gains on chromosomes 7, 8, 13 and 20, and losses on chromosomes 1p, 8p, 17p and 18, a...
BackgroundDiagnosis of low-grade dysplasia (LGD) is important in the management of ulcerative colitis (UC), but it is often difficult to distinguish LGD from inflammatory regenerative epithelium. The unfolded protein response (UPR) is activated in inflammatory bowel disease and malignancies. We aimed to identify a UPR-related gene that is involved in the development of non-UC and UC-associated colorectal cancer (CRC), and to investigate whether the target gene is useful for the diagnosis of LGD.MethodsUsing our microarray gene expression database of 152 CRCs, we identified activating transcription factor 6 (ATF6) as a target gene. Immunohistochemistry (IHC) of ATF6 were analyzed in 137 surgically resected CRCs, 95 endoscopically resected adenomas and pTis cancers, and 136 samples from 51 UC patients (93 colitis without neoplasia, 31 dysplasia, and 12 UC-associated CRC). The diagnostic accuracy of ATF6 and p53 as markers of LGD was assessed.ResultsATF6 expression was detectable in all CRCs but not in normal colonic mucosa, was elevated with increase in cellular atypia (adenoma with moderate atypia < severe atypia < pTis CRC, p < 0.001), and higher in dysplasia and CRC than in non-neoplastic colitis (p < 0.001). Notably, the difference between colitis and LGD was significant. Compared to p53-IHC, ATF6-IHC had better diagnostic accuracy for distinguishing LGD from background inflammatory mucosa (sensitivity 70.8 vs. 16.7%, specificity 78.5 vs.71.0%, respectively).ConclusionsATF6 was expressed in lesions undergoing pre-cancerous atypical change in both non-UC and UC-associated CRC and may be used to distinguish LGD from inflammatory regenerative epithelium in UC patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-017-1387-1) contains supplementary material, which is available to authorized users.
Using MDCT, the optimal cutoff value of minor axis length for predicting mesorectal and lateral pelvic lymph node metastases in patients with distal rectal cancer was 6 mm. The accuracy of MDCT was satisfactory for predicting lateral pelvic lymph node metastasis.
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