Although disease stage is the most relevant factor influencing treatment choice in locally advanced radically resected colorectal cancer, it is not uncommon to observe disease relapse in patients with apparent low risk stage that are usually excluded from an adjuvant therapy. On the contrary we also know that some patients with high risk stage are not likely to relapse independently from medical treatment received. Preclinical data suggested that cancer stem cells may influence the biological behaviour of many solid tumours including colorectal cancer. We tested a panel of genetic markers of stemness in resected Dukes stage B and C colorectal cancer and their impact on prognosis. We performed k-means unsupervised clustering (K = 2) using the mRNA expression data of 66 genes. The algorithm divided the patients into two groups (A and B) and most of the patients clustered in a manner consistent with relapse free survival, defined as the time between primary surgery and first radiological sign of metastatic involvement or patients death, whichever came first. A total of 62 patients were analysed (46, 74% stage II and 16, 26% stage III), 36 (58%) patients relapsed during the follow-up period (range 1.63-86.5 months). Respectively 12 (19%) and 50 (81%) patients were allocated into group A and B. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p = 0.0296). Interestingly enough, even if group A had a worse outcome in terms of risk of relapse, an higher percentage of stage II patients could be found in this group (83%) when compared with the group B (52%). Among of all genes tested, those with the higher “weight” in determining allocation into one of the two groups were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis supports the idea that, other than (or maybe more than) stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients.
CANCER STEM CELL GENETIC PROFILE AS PREDICTOR OF RELAPSE IN RADICALLY RESECTED COLORECTAL CANCER / Giampieri, Riccardo; Scartozzi, Mario; Piva, Francesco; Loretelli, Cristian; Mandolesi, Alessandra; Faloppi, Luca; Bianconi, Maristella; Bittoni, Alessandro; Bearzi, Italo; Cascinu, Stefano. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 23:(2012), pp. ix86-ix87. (Intervento presentato al convegno 37th Congress of the European-Society-for-Medical-Oncology (ESMO) tenutosi a Vienna, AUSTRIA nel SEP 28 - OCT 02, 2012) [10.1093/annonc/mds391].
CANCER STEM CELL GENETIC PROFILE AS PREDICTOR OF RELAPSE IN RADICALLY RESECTED COLORECTAL CANCER
GIAMPIERI, RICCARDO;SCARTOZZI, MARIO;PIVA, Francesco;LORETELLI, CRISTIAN;MANDOLESI, Alessandra;FALOPPI, LUCA;BIANCONI, MARISTELLA;BITTONI, ALESSANDRO;BEARZI, ITALO;CASCINU, Stefano
2012-01-01
Abstract
Although disease stage is the most relevant factor influencing treatment choice in locally advanced radically resected colorectal cancer, it is not uncommon to observe disease relapse in patients with apparent low risk stage that are usually excluded from an adjuvant therapy. On the contrary we also know that some patients with high risk stage are not likely to relapse independently from medical treatment received. Preclinical data suggested that cancer stem cells may influence the biological behaviour of many solid tumours including colorectal cancer. We tested a panel of genetic markers of stemness in resected Dukes stage B and C colorectal cancer and their impact on prognosis. We performed k-means unsupervised clustering (K = 2) using the mRNA expression data of 66 genes. The algorithm divided the patients into two groups (A and B) and most of the patients clustered in a manner consistent with relapse free survival, defined as the time between primary surgery and first radiological sign of metastatic involvement or patients death, whichever came first. A total of 62 patients were analysed (46, 74% stage II and 16, 26% stage III), 36 (58%) patients relapsed during the follow-up period (range 1.63-86.5 months). Respectively 12 (19%) and 50 (81%) patients were allocated into group A and B. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p = 0.0296). Interestingly enough, even if group A had a worse outcome in terms of risk of relapse, an higher percentage of stage II patients could be found in this group (83%) when compared with the group B (52%). Among of all genes tested, those with the higher “weight” in determining allocation into one of the two groups were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis supports the idea that, other than (or maybe more than) stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
