scholarly journals KRT17 as a prognostic biomarker for stage II colorectal cancer

2019 ◽  
Vol 41 (5) ◽  
pp. 591-599 ◽  
Author(s):  
Daisuke Ujiie ◽  
Hirokazu Okayama ◽  
Katsuharu Saito ◽  
Mai Ashizawa ◽  
Aung Kyi Thar Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Biomarker ◽  
Clinicopathological Features ◽  
Stage Ii ◽  
Positive Staining ◽  
Prognostic Impact ◽  
Rna Seq ◽  
Total N ◽  
Stage Ii Colorectal Cancer

Abstract Adjuvant chemotherapy is considered for patients with stage II colorectal cancer (CRC) characterized by poor prognostic clinicopathological features; however, current stratification algorithms remain inadequate for identifying high-risk patients. To develop prognostic assays, we conducted a step-wise screening and validation strategy using nine cohorts of stage II patients based on multiple platforms, including microarray, RNA-sequencing (RNA-seq) and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tissues. Four microarray datasets (total n = 458) were used as the discovery set to screen for single genes associated with postoperative recurrence. Prognostic values of candidate genes were evaluated in three independent microarray/RNA-seq validation cohorts (n = 89, n = 93 and n = 183, respectively), and then IHC for KRT17 was conducted in two independent FFPE series (n = 110 and n = 44, respectively). We found that high levels of KRT17 transcript expression were significantly associated with poor relapse-free survival (RFS) not only in the discovery set, but also in three validation cohorts, and its prognostic impact was independent of conventional factors by multivariate analyses. Positive staining of KRT17 protein was significantly associated with poor RFS in two independent FFPE cohorts. KRT17 protein expression had independent prognostic impact on RFS in a multivariate model adjusted for conventional variables, including high-risk clinicopathological features. In conclusion, using nine independent cohorts consisting of 997 stage II patients, we identified and validated the expression of KRT17 transcript and KRT17 protein as a robust prognostic biomarker that can discriminate postoperative stage II patients who are at high probability of disease recurrence, providing additional prognostic stratification beyond the currently available high-risk factors.

Mucinous Adenocarcinoma as a High-risk Factor in Stage II Colorectal Cancer: A Propensity Score-matched Study from Japan

2020 ◽  
Vol 40 (3) ◽  
pp. 1651-1659 ◽  
Author(s):  
LIMING WANG ◽  
YASUMITSU HIRANO ◽  
GREGORY HENG ◽  
TOSHIMASA ISHII ◽  
HIROKA KONDO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
High Risk ◽  
Propensity Score ◽  
Mucinous Adenocarcinoma ◽  
Stage Ii ◽  
High Risk Factor ◽  
Stage Ii Colorectal Cancer ◽  
Matched Study

scholarly journals Prognostic Impact of the Number of Examined Lymph Nodes in Stage II Colorectal Adenocarcinoma: A Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Purun Lei ◽  
Ying Ruan ◽  
Jianpei Liu ◽  
Qixian Zhang ◽  
Xiao Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stage Ii ◽  
Lymph Node Status ◽  
Stage Migration ◽  
Prognostic Impact ◽  
Disease Specific Survival ◽  
Stage Ii Colorectal Cancer ◽  
Disease Specific

Background. Evaluation of lymph node status is critical in colorectal carcinoma (CRC) treatment. However, as patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The aims of this study were to assess the impact of the ELN on the survival of patients with stage II colorectal cancer and to determine the optimal number. Methods. Data from the US Surveillance, Epidemiology, and End Results (SEER) database on stage II resected CRC (1988-2013) were extracted for mathematical modeling as ELN was available since 1988. Relationship between ELN count and stage migration and disease-specific survival was analyzed by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS (Locally Weighted Scatterplot Smoothing) smoother, and the structural break points were determined by the Chow test. An independent cohort of cases from 2014 was retrieved for validation in 5-year disease-specific survival (DSS). Results. An increased ELN count was associated with a higher possibility of metastasis LN detection (OR 1.010, CI 1.009-1.011, p<0.001) and better DSS in LN negative patients (OR 0.976, CI 0.975-0.977, p<0.001). The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p<0.001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p<0.001). The cut-off value of the ELN count in site-specific surgeries was analyzed as 20 nodes in the right hemicolectomy (HR 0.674, CI 0.638-0.713, p<0.001), 19 nodes in left hemicolectomy (HR 0.691, CI 0.639-0.749, p<0.001), and 20 nodes in rectal resection patients (HR 0.671, CI 0.604-0.746, p<0.001), respectively. Conclusions. A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least 21 lymph nodes be examined for accurate diagnosis of stage II colorectal cancer.

Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 499-499
Author(s):  
Junjie Peng ◽  
Yaqi Li ◽  
Yang Feng
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Risk Groups ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer

499 Background: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer. The objective of this study was to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II colorectal cancer. Methods: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II colorectal cancer. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low and high-risk groups and compare the benefit from adjuvant chemotherapy. Results: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs, whereas PD-L1 expression wasn't associated with RFS or OS. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p < 0.001 and p = 0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p = 0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% v 34.3%, p = 0.006). Conclusions: These results may help improve the prognostication of stage II colorectal cancer and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.

JCOG1805 (PanDRa-BD study): A randomized controlled study of adjuvant chemotherapy for stage II colorectal cancer patients at high-risk of developing recurrence according to T-stage and three selected pathological factors (Pn, DR, and BD).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3621-TPS3621
Author(s):  
Megumi Ishiguro ◽  
Hideki Ueno ◽  
Atsuo Takashima ◽  
Junki Mizusawa ◽  
Keita Sasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Multicenter Study ◽  
Prognostic Value ◽  
Stage Ii ◽  
Randomized Controlled ◽  
T Stage ◽  
Stage Ii Colorectal Cancer

TPS3621 Background: Adjuvant chemotherapy for stage II colorectal cancer (CRC) still remains controversial. Although the NCCN and ESMO guidelines recommend adjuvant chemotherapy for patients with “high-risk features,” the survival benefit has not been confirmed. We reviewed the evidence levels for prognostic values of risk factors, because lack of their robustness is a major source of uncertainty regarding the optimal indication of adjuvant chemotherapy. Consequently, on top of the T-stage, three pathological factors—perineural invasion (Pn), tumor budding (BD), and desmoplastic reaction (DR)—were selected as robust risk factors of recurrence. Among the conventional factors, the prognostic value of Pn had been well validated in a multicenter study conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR; Am J Surg Path 2013), but others were deemed suboptimal in terms of the prognostic value. BD and DR are novel tumor- and stroma-factors, respectively, associated with cancer microenvironment at the tumor front. According to the JSCCR and ITBCC 2016 criteria, tumors are graded as BD1, BD2, or BD3. The DR heterogeneity is categorized into Mature, Intermediate, and Immature patterns based on site-specific products of cancer-associated fibroblasts—keloid-like collagen and myxoid stroma. According to a recent prospective multicenter study, BD and DR characterization represent a higher level of prognostic value than other conventional factors (SACURA trial; J Clin Oncol 2019, Br J Cancer 2021). Based on the four selected risk factors, we can exclude the patient group with favorable prognosis (i.e., > 90% of 5-year RFS), which accounts for approximately 40% of the total population, resulting in enabling us to identify the concentrated population of high risk of developing recurrence. Methods: The Japan Clinical Oncology Group (JCOG) launched a randomized controlled phase III trial to evaluate the superiority of adjuvant chemotherapy in terms of relapse-free survival (RFS) over observation only in stage II CRC patients aged 20–80 years having one or more of the following risk factors: pathological T4, Pn, BD3, and non-Mature DR. Patients are randomised, in a 1:1:1 ratio, to [A] observation, [B] capecitabine monotherapy for 6 months, or [C] capecitabine and oxaliplatin (CAPOX) for 3 months. A total of 1680 patients will be accrued from 54 Japanese institutions assuming 3-year RFS with [A] to be 82% and expected 5% increase in 3-year RFS for [B] and [C] with one-sided alpha of 2.5% and power of 80% for each pair comparison. Patient enrollment was started in January 2020 and 170 patients have been enrolled until January 2021. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031190186. Clinical trial information: jRCTs031190186.

Sign in / Sign up

Export Citation Format

Share Document