TY - JOUR
T1 - Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma
T2 - A pilot study
AU - Kalman, Richard
AU - Stawarz, Andrew
AU - Nunes, David
AU - Zhang, Di
AU - Dela Cruz, Mart A.
AU - Mohanty, Arpan
AU - Subramanian, Hariharan
AU - Backman, Vadim
AU - Roy, Hemant K.
N1 - Publisher Copyright:
© 2018 Kalman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/5
Y1 - 2018/5
N2 - Purpose Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. Experimental design A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaf-finized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. Results PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen’s d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. Conclusions High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC.
AB - Purpose Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. Experimental design A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaf-finized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. Results PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen’s d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. Conclusions High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC.
UR - http://www.scopus.com/inward/record.url?scp=85047351050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047351050&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0197427
DO - 10.1371/journal.pone.0197427
M3 - Article
C2 - 29771950
AN - SCOPUS:85047351050
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 5
M1 - e0197427
ER -
