Abstract
The purpose of the current study is to investigate the prognostic significance of M2 isoform of pyruvate kinase (PKM2) mRNA expression loss in patients with operable colon cancer (CC). Two hundred sixty-two specimens from patients with stage-III or high-risk stage-II CC (group-A) treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy (FOLFOX), 118 specimens from metastatic CC patients (group-B) treated with FOLFOX, and 104 metastatic CC patients (group-C) treated with irinotecan-based chemotherapy were analyzed for PKM2, TS, ERCC1, MYC, and NEDD9 mRNA expression, as well as KRAS exon2 and BRAFV600E mutations. High PKM2 mRNA expression was correlated with left-sided located primaries (p = 0.001, group-A; p = 0.003, group-B; p = 0.001, group-C), high-grade tumors (p = 0.001, group-A; p = 0.017, group-B; p = 0.021, group-C), microsatellite-stable tumors (p < 0.001, group-A), pericolic lymph nodes involvement (p = 0.018, group-A), and cMYC mRNA expression (p = 0.002, group-A; p = 0.008, group-B; p = 0.006, group-C). High PKM2 mRNA expression was correlated with significantly lower disease free survival (DFS) (p = 0.002) and overall survival (OS) (p = 0.001) in the group-A. Similarly, PKM2 mRNA expression was associated with significantly decreased progression free survival (PFS) (p = 0.001) and OS (p = 0.001) in group-B. On the contrary, no significant association for the PKM2 mRNA expression has been observed with either PFS (p = 0.612) or OS (p = 0.517) in group-C. To conclude, the current study provides evidence for the prediction of PKM2 mRNA expression oxaliplatin-based treatment resistance.
Highlights
Colorectal cancer (CRC) represents 9% of all malignant tumors in adults [1]
Patients that received postoperative combination adjuvant chemotherapy (CAPOX or FOLFOX) were predominantly males (58%) with a median age of 67 years; 65% of the patients had a primary tumor located in the left colon and 60% were diagnosed with stage
In consideration of the principal role of PKM2 in CRC growth depending on evidence from previous studies [8,10,29], we investigated the interaction of PKM2 expression with known clinic-pathological features, microsatellite instability (MSI) status, and KRAS exon 2 and BRAFV600E mutations, as well as ERCC1, cMYC, NEDD9, and TS mRNA expression
Summary
Colorectal cancer (CRC) represents 9% of all malignant tumors in adults [1]. Even though curative surgical resection shows potential in 70–80% of colon cancer (CC) patients at diagnosis, nearly half of them will develop local or/and metastatic recurrence and will pass away from the Cancers 2020, 12, 2058; doi:10.3390/cancers12082058 www.mdpi.com/journal/cancersCancers 2020, 12, 2058 disease [2] (GLOBOCAN). Colorectal cancer (CRC) represents 9% of all malignant tumors in adults [1]. 50% of the patients with stage-III or high-risk stage-II disease could be treated with surgery alone and adjuvant chemotherapy may prevent relapse in another. Adjuvant chemotherapy with a combination of a fluoropyrimidine (FP) with oxaliplatin (LOHP) is recommended for stage-III or high risk of relapse stage-II colon patients [3]. CAPOX (capecitabine + oxaliplatin) or FOLFOX are among the standard treatment options for metastatic disease [3]. The genetic CRC underpinnings are extremely well studied [4] and a multistep process for the carcinogenesis in the colon epithelium, from normal mucosa to invasive cancer, has been suggested more than twenty years ago [5].
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