TKTL1 as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma and Its Correlation with FDG-PET-CT

Abstract

<b><i>Introduction:</i></b> Glucose metabolism in cancer cells differs from noncancerous cells. The expression of transketolase-like protein 1 (TKTL1), a key enzyme in the glucose metabolism of cancer cells, predicts poor prognosis in several cancer types. We studied TKTL1 as a prognostic tool and whether TKTL1 expression correlates with 18F-FDG-PET-CT among patients with pancreatic ductal adenocarcinoma (PDAC). <b><i>Methods:</i></b> This retrospective study examined two PDAC patient cohorts: 168 patients operated on at Helsinki University Hospital between 2001 and 2011, and 20 patients with FDG-PET-CT results available from the Auria Biobank. We used immunohistochemistry for TKTL1 expression, combining results with clinicopathological data. <b><i>Results:</i></b> Five-year disease-specific survival (DSS) was slightly but not significantly better in patients with a high versus low TKTL1 expression, with DSS of 28.0 versus 17.3%, respectively (<i>p</i> = 0.123). TKTL1 served as a marker of a better prognosis in patients over 65 years old (<i>p</i> = 0.012) and among those with TNM class M1 (<i>p</i> = 0.018), stage IV disease (<i>p</i> = 0.027), or perivascular invasion (<i>p</i> = 0.008). <b><i>Conclusions:</i></b> Our study shows that TKTL1 cannot be used as a prognostic factor in PDAC with the exception of elderly patients and those with advanced disease. The correlation of TKTL1 with 18F-FDG-PET-CT requires further study in a larger patient cohort.

Transketolase Serves as a Biomarker for Poor Prognosis in Human Lung Adenocarcinoma

“…This is probably due to the insufficient sample size of stage IV. But a similar pattern was also found in colorectal cancer and pancreatic ductal adenocarcinoma 15 , 20 . The PPP and glycolysis are interlinked, which are mechanistically relevant for the dynamic regulation of migration versus proliferation 41 .…”

“…However, a recent study of a large cohort of colorectal cancer patients with liver metastases found that TKTL1 may serve as a reverse prognostic significance 20 . In addition, TKTL1 served as a marker of a better prognosis in patients over 65 years old and among those with TNM class M1, stage IV disease, or perivascular invasion had already been described in pancreatic ductal adenocarcinoma 15 . In lung adenocarcinoma disease, it remains unclear if a high expression alone indicates a better prognosis or if it reflects other invasiveness-reducing characteristics that we have yet to identify.…”

“…Transketolase (TKT) is the main enzyme involved in non-oxidative PPP, which involves three human genes: transketolase (TKT) and two TKT-like genes (TKTL1 and TKTL2) 14 . Several studies had been performed to determine the associations between the TKT genes family and cancer carcinogenesis 15 - 18 . The expression of TKT in breast cancer was elevated, companied with the poor prognosis 19 .…”

TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression

“…The TKTL1 isoenzyme is missing 38 amino acids in the active site [ 3 ] and increased expression of TKT and its isoform TKTL1 has been reported in different types of cancers [ 4 , 5 , 6 , 7 ], and is related to malignant transformation [ 8 ] and poor prognosis [ 9 , 10 , 11 , 12 ]. Evidence across several cancer tissues up until now have highlighted that TKTL1 is tightly linked to adaptation to hypoxia and its overexpression has been correlated with resistance to ionizing radiation and chemotherapy [ 13 ] as well as to the “Warburg effect” [ 14 ].…”