Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Gastric Cancer | Research article

KK-LC-1 may be an effective prognostic biomarker for gastric cancer

Authors: Jun Ji, Jiahui Chen, Anqiang Wang, Wei Zhang, Hongge Ju, Yang Liu, Leping Li

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

Background

The objective of the study was to detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyse the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis.

Methods

All of the 94 patients in this study were GC patients who underwent surgical resection. KK-LC-1 protein expression in GC tissue was detected by immunohistochemistry. This report applies the histological score (H-score) to evaluate KK-LC-1 expression. To calculate this indicator, the number of positive cells in each section and their staining intensity were converted to corresponding values. The expression of KK-LC-1 in the cytoplasm of cancer and normal tissues was scored to obtain their respective H values. The chi-square test, Kaplan-Meier method and Cox regression were used to analyse the linear association between KK-LC-1 expression and clinicopathological data and prognosis.

Results

In the cytoplasm, KK-LC-1 expression in tumour tissues was significantly higher than that in normal tissues (P < 0.001). Using the median H-score as the cut-off value, we discovered that GC patients with high levels of KK-LC-1 expression in the cytoplasm had favourable overall survival (OS) (P = 0.016), and this result was statistically significant in the Cox regression analysis. Additionally, a negative correlation was found between KK-LC-1 protein expression and the pathological grade of the tumour (P = 0.036), with significantly more KK-LC-1 protein expression observed in the intestinal type of GC than in the diffuse type (P = 0.008).

Conclusions

Our research data showed that KK-LC-1 expression was greater in GC tissues than in normal tissues, and higher KK-LC-1 expression was associated with longer OS of GC patients. KK-LC-1 can be used as a biomarker for a good prognosis in GC patients.
Literature
1.
Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, Tsujitani S, Ono H, Tanabe S, Fukagawa T, Nunobe S, Kakeji Y, Nashimoto A. Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese gastric Cancer association (2001-2007). Gastric Cancer. 2018;21(1):144–54.CrossRef
2.
Shi C, Liu B, Yan J, Liu H, Pan Z, Yao W, Yan F, Zhang H. Gastric Cancer: preoperative TNM staging with individually adjusted computed tomography scanning phase. J Comput Assist Tomogr. 2016;40(1):160–6.CrossRef
3.
Aoyagi K, Kouhuji K, Kizaki J, Isobe T, Hashimoto K, Shirouzu K. Molecular targeting to treat gastric cancer. World J Gastroenterol. 2014;20(38):13741–55.CrossRef
4.
Pectasides D, Mylonakis A, Kostopoulou M, Papadopoulou M, Triantafillis D, Varthalitis J, Dimitriades M, Athanassiou A. CEA, CA 19-9, and CA-50 in monitoring gastric carcinoma. Am J Clin Oncol. 1997;20(4):348–53.CrossRef
5.
Aloe S, D'Alessandro R, Spila A, Ferroni P, Basili S, Palmirotta R, Carlini M, Graziano F, Mancini R, Mariotti S, Cosimelli M, Roselli M, Guadagni F. Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer. Int J Biol Markers. 2003;18(1):21–7.CrossRef
6.
Genc CG, Falconi M, Partelli S, Muffatti F, van Eeden S, Doglioni C, Klumpen HJ, van Eijck C, Nieveen VDE. Recurrence of pancreatic neuroendocrine tumors and survival predicted by Ki67. Ann Surg Oncol. 2018;25(8):2467–74.CrossRef
7.
Sohn BH, Hwang JE, Jang HJ, Lee HS, Oh SC, Shim JJ, Lee KW, Kim EH, Yim SY, Lee SH, Cheong JH, Jeong W, Cho JY, Kim J, Chae J, Lee J, Kang WK, Kim S, Noh SH, Ajani JA, Lee JS. Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project. Clin Cancer Res. 2017.
8.
Yang TS, Yang XH, Wang XD, Wang YL, Zhou B, Song ZS. MiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTEN. Cancer Cell Int. 2013;13(1):68.CrossRef
9.
Ha SY, Lee J, Kang SY, Do IG, Ahn S, Park JO, Kang WK, Choi MG, Sohn TS, Bae JM, Kim S, Kim M, Kim S, Park CK, Ignatius OS, Kim KM. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod Pathol. 2013;26(12):1632–41.CrossRef
10.
Lee SJ, Lee J, Park SH, Park JO, Lim HY, Kang WK, Park YS, Kim ST. C-MET overexpression in colorectal Cancer: a poor prognostic factor for survival. Clin Colorectal Cancer. 2018;17(3):165–9.CrossRef
11.
Pasquini G, Giaccone G. C-MET inhibitors for advanced non-small cell lung cancer. Expert Opin Investig Drugs. 2018;27(4):363–75.CrossRef
12.
Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22–32.CrossRef
13.
Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ. Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005;5(8):615–25.CrossRef
14.
Jager D, Jager E, Knuth A. Immune responses to tumour antigens: implications for antigen specific immunotherapy of cancer. J Clin Pathol. 2001;54(9):669–74.CrossRef
15.
Li G, Miles A, Line A, Rees RC. Identification of tumour antigens by serological analysis of cDNA expression cloning. Cancer Immunol Immunother. 2004;53(3):139–43.CrossRef
16.
Mischo A, Kubuschok B, Ertan K, Preuss KD, Romeike B, Regitz E, Schormann C, de Bruijn D, Wadle A, Neumann F, Schmidt W, Renner C, Pfreundschuh M. Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer. Int J Cancer. 2006;118(3):696–703.CrossRef
17.
Bricard G, Bouzourene H, Martinet O, Rimoldi D, Halkic N, Gillet M, Chaubert P, Macdonald HR, Romero P, Cerottini JC, Speiser DE. Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma. J Immunol. 2005;174(3):1709–16.CrossRef
18.
Groeper C, Gambazzi F, Zajac P, Bubendorf L, Adamina M, Rosenthal R, Zerkowski HR, Heberer M, Spagnoli GC. Cancer/testis antigen expression and specific cytotoxic T lymphocyte responses in non small cell lung cancer. Int J Cancer. 2007;120(2):337–43.CrossRef
19.
Ghafouri-Fard S, Modarressi MH. Cancer-testis antigens: potential targets for cancer immunotherapy. Arch Iran Med. 2009;12(4):395–404.PubMed
20.
Gjerstorff MF, Andersen MH, Ditzel HJ. Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget. 2015;6(18):15772–87.CrossRef
21.
Ogata K, Aihara R, Mochiki E, Ogawa A, Yanai M, Toyomasu Y, Ando H, Ohno T, Asao T, Kuwano H. Clinical significance of melanoma antigen-encoding gene-1 (MAGE-1) expression and its correlation with poor prognosis in differentiated advanced gastric cancer. Ann Surg Oncol. 2011;18(4):1195–203.CrossRef
22.
Honda T, Tamura G, Waki T, Kawata S, Terashima M, Nishizuka S, Motoyama T. Demethylation of MAGE promoters during gastric cancer progression. Br J Cancer. 2004;90(4):838–43.CrossRef
23.
Shida A, Futawatari N, Fukuyama T, Ichiki Y, Takahashi Y, Nishi Y, Kobayashi N, Yamazaki H, Watanabe M. Frequent high expression of Kita-Kyushu lung Cancer Antigen-1 (KK-LC-1) in gastric Cancer. Anticancer Res. 2015;35(6):3575–9.PubMed
24.
Futawatari N, Fukuyama T, Yamamura R, Shida A, Takahashi Y, Nishi Y, Ichiki Y, Kobayashi N, Yamazaki H, Watanabe M. Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen. World J Gastroenterol. 2017;23(46):8200–6.CrossRef
25.
Chen J, Wang A, Ji J, Zhou K, Bu Z, Lyu G, Ji J. An innovative prognostic model based on four genes in Asian patient with gastric Cancer. Cancer Res Treat. 2021;53(1):148–61.CrossRef
26.
Yeo W, Chan SL, Mo FK, Chu CM, Hui JW, Tong JH, Chan AW, Koh J, Hui EP, Loong H, Lee K, Li L, Ma B, To KF, Yu SC. Phase I/II study of temsirolimus for patients with unresectable hepatocellular carcinoma (HCC)- a correlative study to explore potential biomarkers for response. BMC Cancer. 2015;15:395.CrossRef
27.
Specht E, Kaemmerer D, Sanger J, Wirtz RM, Schulz S, Lupp A. Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms. Histopathology. 2015;67(3):368–77.CrossRef
28.
Liang PI, Li CF, Chen LT, Sun DP, Chen TJ, Hsing CH, Hsu HP, Lin CY. BCL6 overexpression is associated with decreased p19 ARF expression and confers an independent prognosticator in gallbladder carcinoma. Tumour Biol. 2014;35(2):1417–26.CrossRef
29.
Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, Flowers JL, McCarty KJ. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986;46(10):5419–25.PubMed
30.
Fukuyama T, Futawatari N, Yamamura R, Yamazaki T, Ichiki Y, Ema A, Ushiku H, Nishi Y, Takahashi Y, Otsuka T, Yamazaki H, Koizumi W, Yasumoto K, Kobayashi N. Expression of KK-LC-1, a cancer/testis antigen, at non-tumour sites of the stomach carrying a tumour. Sci Rep. 2018;8(1):6131.CrossRef
31.
Paret C, Simon P, Vormbrock K, Bender C, Kolsch A, Breitkreuz A, Yildiz O, Omokoko T, Hubich-Rau S, Hartmann C, Hacker S, Wagner M, Roldan DB, Selmi A, Tureci O, Sahin U. CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer. Oncotarget. 2015;6(28):25356–67.CrossRef
32.
Watanabe M, Kato J, Inoue I, Yoshimura N, Yoshida T, Mukoubayashi C, Deguchi H, Enomoto S, Ueda K, Maekita T, Iguchi M, Tamai H, Utsunomiya H, Yamamichi N, Fujishiro M, Iwane M, Tekeshita T, Mohara O, Ushijima T, Ichinose M. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer. 2012;131(11):2632–42.CrossRef
33.
Nardone G, Rocco A, Malfertheiner P. Helicobacter pylori and molecular events in precancerous gastric lesions. Aliment Pharm Ther. 2004;20(3):261–70.CrossRef
34.
Lee T, Tanaka H, Ohira M, Okita Y, Yoshii M, Sakurai K, Toyokawa T, Kubo N, Muguruma K, Tanaka S, Ohsawa M, Hirakawa K. Clinical impact of the extent of lymph node micrometastasis in undifferentiated-type early gastric Cancer. Oncology. 2014;86(4):244–52.CrossRef
35.
Zhang W, Barger CJ, Link PA, Mhawech-Fauceglia P, Miller A, Akers SN, Odunsi K, Karpf AR. DNA hypomethylation-mediated activation of Cancer/testis antigen 45 (CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer. Epigenetics-US. 2015;10(8):736–48.CrossRef
36.
Xie K, Zhang K, Kong J, Wang C, Gu Y, Liang C, Jiang T, Qin N, Liu J, Guo X, Huo R, Liu M, Ma H, Dai J, Hu Z. Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma. Cancer Med. 2018;7(1):157–66.CrossRef
Metadata
Title
KK-LC-1 may be an effective prognostic biomarker for gastric cancer
Authors
Jun Ji
Jiahui Chen
Anqiang Wang
Wei Zhang
Hongge Ju
Yang Liu
Leping Li
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07974-7

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue

Study protocol

A randomized phase II study of S-1 monotherapy versus cisplatin with vinorelbine for completely resected stage II/IIIA non-small cell lung cancer: rationale and study protocol design for the LOGIK1702 study

Study protocol

Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS)

Research

Real-world study of the impact of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) on quality of life and productivity in Europe

Research

Changes in vitamin D and calcium metabolism markers in patients undergoing adjuvant chemotherapy for breast cancer

Research

Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

Research article

CircCDC45 promotes the malignant progression of glioblastoma by modulating the miR-485-5p/CSF-1 axis

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits