PMID- 29552193 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-1074 (Print) IS - 1792-1082 (Electronic) IS - 1792-1074 (Linking) VI - 15 IP - 4 DP - 2018 Apr TI - Effect of HK2, PKM2 and LDHA on Cetuximab efficacy in metastatic colorectal cancer. PG - 5553-5560 LID - 10.3892/ol.2018.8005 [doi] AB - Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis. A total of 68 patients were included; 33 received cetuximab plus chemotherapy as first-line therapy, and the rest, as second- or later-line therapy. HK2 expression levels were increased in cancer compared with normal tissue (75.4% vs. 40%; P<0.001), however PKM2 (P=0.243) and LDHA (P=0.067) expression levels were not. For progression-free survival (PFS) with first-line cetuximab plus chemotherapy, patients with high HK2 expression exhibited longer PFS compared with those with low HK2 expression (23.9 months vs. 6.9 months; P=0.021). However, this positive association was absent in 35 cases administered first-line chemotherapy alone (13.4 months vs. 13.5 months; P=0.539). LDHA expression was associated with the PFS of patients receiving first-line chemotherapy (18.3 and 10.1 months for high and low expression, respectively; P=0.005), whereas this association was absent in cetuximab plus chemotherapy cases (19.9 months vs. 12 months; P=0.522). Furthermore, high LDHA expression correlated with high overall response rate (ORR) (72.2% vs. 15.4%, P=0.006) for chemotherapy, however not disease control rate (DCR) (P=0.074). Neither DCR nor ORR were associated with HK2 expression. PKM2 expression did not affect PFS, DCR or ORR. LDHA expression (P=0.005), pathological differentiation (P=0.019) and synchronous/metachronous metastasis (P=0.014) were independent predictive factors of PFS for all first-line patients, and tumor differentiation (P=0.002) was associated with overall survival (OS) in multivariate analysis. HK2, PKM2 and LDHA did not impact OS. It was concluded that HK2 expression was increased in colorectal cancer tissue and may predict cetuximab efficacy and LDHA for chemotherapy treatment of mCRC. FAU - Wang, Haohua AU - Wang H AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Peng, Roujun AU - Peng R AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Chen, Xiuxing AU - Chen X AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Jia, Rui AU - Jia R AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Radiation Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Huang, Chunyue AU - Huang C AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Radiation Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Huang, Yuanyuan AU - Huang Y AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Xia, Liangping AU - Xia L AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. FAU - Guo, Guifang AU - Guo G AD - VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. AD - Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China. LA - eng PT - Journal Article DEP - 20180208 PL - Greece TA - Oncol Lett JT - Oncology letters JID - 101531236 PMC - PMC5840691 OTO - NOTNLM OT - HK-II OT - LDHA OT - PKM2 OT - cetuximab OT - mCRC EDAT- 2018/03/20 06:00 MHDA- 2018/03/20 06:01 PMCR- 2018/02/08 CRDT- 2018/03/20 06:00 PHST- 2017/08/12 00:00 [received] PHST- 2018/01/11 00:00 [accepted] PHST- 2018/03/20 06:00 [entrez] PHST- 2018/03/20 06:00 [pubmed] PHST- 2018/03/20 06:01 [medline] PHST- 2018/02/08 00:00 [pmc-release] AID - OL-0-0-8005 [pii] AID - 10.3892/ol.2018.8005 [doi] PST - ppublish SO - Oncol Lett. 2018 Apr;15(4):5553-5560. doi: 10.3892/ol.2018.8005. Epub 2018 Feb 8.