Review Article

Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

Table 1

Studies showing DNA microarray gene expression profile predictive of response to CRT in LARC.

StudySpecimen patientsValidation groupRadiotherapy dose
Chemotherapy
Response assessmentIdentified genes: more relevant genesOutcome

Ghadimi et al. 2005 [9]Tumor tissue biopsy 30No50.4 Gy/28 fractions
5FU
Downsizing54 genes: SMC1, CLMN, CDC42BPA, and FLNBGroup prediction 83%

Watanabe et al. 2006 [10]Tumor tissue biopsy5217 50.4 Gy
Japanese Classification of Colorectal Carcinoma33 genes  
(i) Overexpressed: LUM, THBS2, and LGALS1  
(ii) Downregulated: CYP40 and GPX2
Class prediction 82.4%,  
sensitivity 50%,  
specificity 100%,  
PPV 100%,  
NPV 76.6%

Kim et al. 2007 [11]Tumor tissue biopsy311550.4 Gy/28 fractions
5FU + LV/capecitabine/
capecitabine + irinotecan
Dworak regression grade95 genes: TYMS and RAD23BPrecision 87%,  
sensitivity 100%,  
specificity 82%

Rimkus et al. 2008 [12]Tumor tissue biopsy43No45 Gy
5FU
Becker regression grade42 genes  
(i) Overexpressed: CASP1, SLC35E1, CCNK, STAT2, and ETS2  
(ii) Downregulated: TDE1, USP42, M-RIP, and FREM1
Accuracy 81%,  
sensitivity 71%,  
specificity 86%,  
PPV 71%,  
NPV 86%

Nishioka et al. 2011 [13]Tumor tissue biopsy17340 Gy/20 fractions
S1
Japanese Classification of Colorectal Carcinoma17 genes: MMP7, MMP14, MMP9, MMP1, MMP16, and RRM1

Casado et al. 2011 [14] Tumor tissue biopsy  
formalin-fixed paraffin-embedded biopsies
25  

94
50.4 Gy/28 fractions
25 oxaliplatin + raltitrexed  
94 different treatment
Dworak regression grade24 genes: genetic profile of 13:  
(i) 6 overexpressed: ALDH1A1, CDKN1 1, FOS, RELB, STAT3, and TFF3  
(ii) 7 downregulated: BAK, MLH1, TYMS, CKB, GPX2, HIG2, and PH-4
Nonresponders:  
accuracy 86%,  
sensitivity 87%,  
specificity 82%

Palma et al. 2013 [8]Blood sample27850.4 Gy/28 fractions
Capecitabine/capecitabine + oxaliplatin
Mandard regression grade8 genes: FALZ

Palma et al. 2014 [7]Tumor tissue biopsy26850.4 Gy/28 fractions
Capecitabine/capecitabine + oxaliplatin
Mandard regression grade257 genes: c-MYC, GNG4, POLA, and RRM1 Accuracy 85%,  
sensitivity 60%,  
specificity 100%,  
PPV 100%,  
NPV 80%

Gantt et al. 2014 [15]Tumor tissue biopsy361050.4 Gy/30 fractions
5FU
American Joint Committee on Cancer183 genes up- and downregulated: RAD50No response:  
sensitivity 33%,  
specificity 100%

Watanabe et al. 2014 [16]Tumor tissue biopsy461650.4 Gy/28 fractions
Tegafur-uracil + leucovorin
Japanese Classification of Colorectal Carcinoma22 probes (18 genes): signature LRRIQ3, FRMD3, SAMD5, and TMC7Accuracy 81.3%,  
sensitivity 100%, specificity 62.5%,  
PPV 72.7%,  
NPV 100%