qRT‐PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes—An improved method for assessment of tumor stage and prognosis

Abstract

One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT‐PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, −1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3‐year follow‐up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, −1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42‐12.69, P = .01], while pTN‐stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.

LGR6 is a prognostic biomarker for less differentiated tumors in lymph nodes of colon cancer patients

“…Another complicating factor for the microscopic methods is selection of LNs for examination of presence of stem cells and assessment of stem cell numbers. The LNs of a single patient can differ considerably regarding the number of tumor cells and the risk factors these cells express ( 6 ). The fact that current guidelines for determination of metastasis status (pN-stage) requires examination of a minimum of 12 LNs points out the fact that LNs of one patient vary considerably in tumor burden ( 42 , 43 ).…”

“…Biomarker mRNA analysis is a very promising alternative allowing analysis of the entire LN volume and analysis of a combination of biomarkers that characterize different properties of the tumors that can be combined in a kit. ColoNode, which combines analysis of mRNAs of CEA (CEACAM5), Kallikrein Related Peptidase 6 (KLK6), Solute Carrier Family 35 Member D3 (SLC35D3), Mucin 2 (MUC2) and Periostin (POSTN) of half the LN volume is a successful colon cancer (CC) prognostic test that surpasses histopathology in identifying patients that will relapse and in addition grades patients with different degrees of risk ( 6 ). The study identified two distinct group of patients, one which should be recommended postoperative adjuvant treatment and another which should be left untreated.…”

Extracellular vesicles isolated from curcumin-medium weakened RKO cell proliferation and migration

“…Colorectal cancer remains a non-negligible cause of cancer-related death ( 16 - 18 ). Surgical therapy is less effective in advanced colorectal cancer patients than those early patients ( 19 ). Additional therapy is required to delay the progression of colorectal cancer, including cell proliferation suppression, apoptosis facilitation, and cell migration inhibition.…”

Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2

“…POSTN is, however, not expressed in the tumor cells. Still, elevated POSTN mRNA levels in LNs from CC patients is an important contributor in ColoNode assay being one of five biomarkers in the two-triplex assay for prediction of tumor recurrence in CC ( 37 ).…”