Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

被引:7
作者
He, Dan-ni [1 ,2 ]
Wang, Na [1 ,2 ,3 ]
Wen, Xiao-Ling [1 ,3 ]
Li, Xu-Hua [1 ,3 ]
Guo, Yu [1 ,3 ]
Fu, Shu-heng [1 ,3 ]
Xiong, Fei-fan [1 ,3 ]
Wu, Zhe-yu [2 ]
Zhu, Xu [1 ,3 ]
Gao, Xiao-ling [4 ]
Wang, Zhen-zhen [1 ,2 ,3 ]
Wang, Hong-jiu [1 ,2 ,3 ]
机构
[1] Hainan Med Univ, Coll Biomed Informat & Engn, Key Lab Trop Translat Med, Minist Educ, Haikou, Peoples R China
[2] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Peoples R China
[3] Hainan Med Univ, Coll Biomed Informat & Engn, Haikou, Peoples R China
[4] Hainan Gen Hosp, Med Lab Ctr, Haikou, Peoples R China
基金
中国国家自然科学基金;
关键词
pan-cancer; multi-omics; early recurrence; early metastasis; potential biomarkers; DIAGNOSIS; BIOMARKER; THERAPY; CELLS;
D O I
10.3389/fgene.2023.1061364
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher's exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.
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页数:21
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共 54 条
[1]   Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].
Abbosh, Christopher ;
Birkbak, Nicolai J. ;
Wilson, Gareth A. ;
Jamal-Hanjani, Mariam ;
Constantin, Tudor ;
Salari, Raheleh ;
Le Quesne, John ;
Moore, David A. ;
Veeriah, Selvaraju ;
Rosenthal, Rachel ;
Marafioti, Teresa ;
Kirkizlar, Eser ;
Watkins, Thomas B. K. ;
McGranahan, Nicholas ;
Ward, Sophia ;
Martinson, Luke ;
Riley, Joan ;
Fraioli, Francesco ;
Al Bakir, Maise ;
Gronroos, Eva ;
Zambrana, Francisco ;
Endozo, Raymondo ;
Bi, Wenya Linda ;
Fennessy, Fiona M. ;
Sponer, Nicole ;
Johnson, Diana ;
Laycock, Joanne ;
Shafi, Seema ;
Czyzewska-Khan, Justyna ;
Rowan, Andrew ;
Chambers, Tim ;
Matthews, Nik ;
Turajlic, Samra ;
Hiley, Crispin ;
Lee, Siow Ming ;
Forster, Martin D. ;
Ahmad, Tanya ;
Falzon, Mary ;
Borg, Elaine ;
Lawrence, David ;
Hayward, Martin ;
Kolvekar, Shyam ;
Panagiotopoulos, Nikolaos ;
Janes, Sam M. ;
Thakrar, Ricky ;
Ahmed, Asia ;
Blackhall, Fiona ;
Summers, Yvonne ;
Hafez, Dina ;
Naik, Ashwini .
NATURE, 2017, 545 (7655) :446-+
[2]   Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative [J].
Aftimos, Philippe ;
Oliveira, Mafalda ;
Irrthum, Alexandre ;
Fumagalli, Debora ;
Sotiriou, Christos ;
Gal-Yam, Einav Nili ;
Robson, Mark E. ;
Ndozeng, Justin ;
Di Leo, Angelo ;
Ciruelos, Eva M. ;
de Azambuja, Evandro ;
Viale, Giuseppe ;
Scheepers, Elsemieke D. ;
Curigliano, Giuseppe ;
Bliss, Judith M. ;
Reis-Filho, Jorge S. ;
Colleoni, Marco ;
Balic, Marija ;
Cardoso, Fatima ;
Albanell, Joan ;
Duhem, Caroline ;
Marreaud, Sandrine ;
Romagnoli, Dario ;
Rojas, Beatriz ;
Gombos, Andrea ;
Wildiers, Hans ;
Guerrero-Zotano, Angel ;
Hall, Peter ;
Bonetti, Andrea ;
Larsson, Karolina Fs ;
Degiorgis, Martina ;
Khodaverdi, Silvia ;
Greil, Richard ;
Sverrisdottir, Asgerdur ;
Paoli, Marta ;
Seyll, Ethel ;
Loibl, Sibylle ;
Linderholm, Barbro ;
Zoppoli, Gabriele ;
Davidson, Nancy E. ;
Johannsson, Oskar Th ;
Bedard, Philippe L. ;
Loi, Sherene ;
Knox, Susan ;
Cameron, David A. ;
Harbeck, Nadia ;
Montoya, Maite Lasa ;
Brandao, Mariana ;
Vingiani, Andrea ;
Caballero, Carmela .
CANCER DISCOVERY, 2021, 11 (11) :2796-2811
[3]   Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1 in stem cell homing and myocardial repair: Potential impact of dipeptidyl peptidase-4 inhibitors [J].
Anderluh, Marko ;
Kocic, Gordana ;
Tomovic, Katarina ;
Kocic, Radivoj ;
Deljanin-Ilic, Marina ;
Smelcerovic, Andrija .
PHARMACOLOGY & THERAPEUTICS, 2016, 167 :100-107
[4]   Systematic pan-cancer analysis of tumour purity [J].
Aran, Dvir ;
Sirota, Marina ;
Butte, Atul J. .
NATURE COMMUNICATIONS, 2015, 6
[5]   Tumor Microenvironment [J].
Arneth, Borros .
MEDICINA-LITHUANIA, 2020, 56 (01)
[6]   Molecular correlates and therapeutic targets in T cell-inflamed versus non-T cell-inflamed tumors across cancer types [J].
Bao, Riyue ;
Stapor, Daniel ;
Luke, Jason J. .
GENOME MEDICINE, 2020, 12 (01)
[7]   Cancer-associated mucins: role in immune modulation and metastasis [J].
Bhatia, Rakesh ;
Gautam, Shailendra K. ;
Cannon, Andrew ;
Thompson, Christopher ;
Hall, Bradley R. ;
Aithal, Abhijit ;
Banerjee, Kasturi ;
Jain, Maneesh ;
Solheim, Joyce C. ;
Kumar, Sushil ;
Batra, Surinder K. .
CANCER AND METASTASIS REVIEWS, 2019, 38 (1-2) :223-236
[8]   PROGNOSTIC VALUE OF PATHOLOGICAL CHARACTERISTICS OF COLORECTAL-CANCER [J].
BOSMAN, FT .
EUROPEAN JOURNAL OF CANCER, 1995, 31A (7-8) :1216-1221
[9]   Early detection of cancer using circulating tumor DNA: biological, physiological and analytical considerations [J].
Bronkhorst, Abel Jacobus ;
Ungerer, Vida ;
Holdenrieder, Stefan .
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2020, 57 (04) :253-269
[10]   Prognostic and predictive factors in early-stage breast cancer [J].
Cianfrocca, M ;
Goldstein, LJ .
ONCOLOGIST, 2004, 9 (06) :606-616