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In American journal of physiology. Cell physiology

Some patients treated for ductal carcinoma in situ (DCIS) of the breast will experience cancer recurrences, whereas other patients will not. Unfortunately, current techniques cannot identify which pre-invasive lesions will lead to recurrent cancer. Because the mechanism of cancer recurrence is unknown, it is difficult to design a test that detects its activity. We propose that certain pentose phosphate pathway enzymes, glutathione synthesis enzymes, and RhoA cluster at the epithelial cell periphery during cancer recurrences. Enzyme clustering enhances metabolic flux. Using fluorescence microscopy we show that phosphophorylated glucose transporter type-1, transketolase-like protein-1, glutathione synthetase, GTP-loaded RhoA, and RhoA accumulate at the epithelial cell periphery in biopsies of women who will suffer recurrences, but not in samples from women who will not experience recurrences as judged using 2x2 contingency tables. A machine study of individual cribriform, papillary, micropapillary, and comedo forms of DCIS demonstrated 97% precision and 95% recall in the detection of samples from women will not experience a recurrence and a 90% precision and 95% recall in the detection of lesions that become recurrent. A holdout study of these patients showed 73% true negatives, 18% true positives, 4% false positives, and 4% false negatives at a 50% threshold. This work suggests mechanistic features of recurrences that may contribute to a new clinical test distinguishing high from low recurrence risk DCIS patients.

Kraft Alexandra M, Petty Howard R

2020-Sep-09

Fluorescence microscopy, Glucose transporter, Intracellular location/trafficking, RhoA, machine learning