Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.
OBJECTIVE
Recent evidence suggests that the human kallikrein 10 (KLK10) gene is differentially regulated in endocrine-related tumors and has potential as diagnostic and/or prognostic marker; however, KLK10 expression has never been investigated in gastrointestinal cancers. The aims of this study were to demonstrate expression and single nucleotide polymorphisms of KLK10 in colorectal cancer (CRC) and gastric cancer (GC), and to correlate the relative KLK10 expression level with clinicopathological factors of CRC and GC.


METHODS
Between March 2004 and January 2005, 63 patients with histologically confirmed CRC and 36 with GC were recruited into the study. Using quantitative real-time (qRT) RT-PCR and Western blot, KLK10 expression in tumor and non-tumor colorectal and gastric tissues was determined at the mRNA and protein levels. KLK10 protein was localized by immunohistochemistry. The KLK10 genomic DNA from 16 cases of paired normal/cancerous colorectal tissues was PCR-amplified and examined for single nucleotide polymorphisms by direct sequencing.


RESULTS
KLK10 mRNA expression was detected by qRT in 61 of 63 (96.8%) CRC specimens and in all GC specimens. KLK10 expression was much higher in tumor tissue than in the corresponding normal mucosal tissue at the mRNA and protein levels (P<0.01). The KLK10 mRNA expression level significantly correlated with lymphatic invasion (P=0.034) and clinical stage of CRC (P=0.025). The KLK10 mRNA expression level significantly correlated with the depth of GC invasion (P=0.018), clinical stage (P=0.045), patient sex (P=0.027) and Lauren type of gastric cancer (P=0.028). No mutations or polymorphisms were detected in exon 1, 2 and 5 of KLK10 gene in CRC. Single nucleotide polymorphisms were identified in codon 50 of exon 3, GCC (alanine) to TCC (serine). The genetic changes of exon 4 were located at codon 106 [GGC (glysine) to GGA (glysine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and codon 149 [CCG (proline) to CTG (leucine)]. All were identical in tumor and corresponding normal tissue DNA from the same individuals.


CONCLUSIONS
KLK10 expression is up-regulated in CRC and GC and higher expression of KLK10 closely correlates with advanced disease stage, which predicts a poorer prognosis; however, further follow-up study is needed.
Feng
Bo
B
Department of General Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai, China. fengbo2022@163.com
Xu
Wei-Bin
WB
Zheng
Min-Hua
MH
Ma
Jun-Jun
JJ
Cai
Qu
Q
Zhang
Yi
Y
Ji
Jun
J
Lu
Ai-Guo
AG
Qu
Ying
Y
Li
Jian-Wen
JW
Wang
Ming-Liang
ML
Hu
Wei-Guo
WG
Liu
Bing-Ya
BY
Zhu
Zheng-Gang
ZG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; C100936:KLK10 protein, human; D007610:Kallikreins