A novel liquid biopsy method can detect kidney cancers with high accuracy, including small, localized tumors which are often curable but for which no early detection method exists, say scientists from Dana-Farber Cancer Institute.
The report in Nature Medicine suggests that if validated in larger trials and applied widely, the noninvasive test could find more early kidney cancers when they haven’t spread, thus reducing the mortality of the disease. “Hopefully we can scale this to a much larger level and detect cancer earlier so we can act earlier,” said Toni Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber and a co-senior author of the study.
It is estimated that 73,750 new kidney cancer cases will be diagnosed in 2020, and about 14,830 will die of the disease. About 35 percent of cancers are diagnosed only after they have spread beyond the kidney and are more difficult to treat. Small, early kidney tumors usually cause no symptoms, and increasingly are found incidentally in scans of the abdomen performed for another purpose. However, there is no imaging or other screening test recommended for the general population to look for early kidney cancers. Initially, a test based on the method described in the new report might be used to screen people with a family history of kidney cancer, or who had a previous kidney cancer, said Choueiri. “We need to be specific first, before making it totally mainstream,” he said.
Noninvasive liquid biopsies, which search for cancer-related DNA shed by tumors into blood or other body fluids, are moving rapidly toward clinical use as a means of early detection for some kinds of tumors. “Kidney cancer is one of the hardest tumors to detect, because it doesn’t shed as much DNA as other tumors,” said Matthew Freedman, a medical oncologist at Dana-Farber and co-senior author of the report.
The test performs well because it can identify abnormal patterns in small amounts of tumor-shed DNA, Freedman added. “It’s a proof of principle that early stage disease is detectable.”
The test was nearly 100 percent accurate when used with blood samples to distinguish patients with kidney cancer from those known to be free of kidney cancer. The method achieves less accuracy in testing urine samples, but the researchers believe that performance can be improved. If the test is validated in larger trials and becomes widely applicable clinically, a urine sample would be even less invasive than a blood draw.
The testing method is known as cell-free methylated DNA immunoprecipitation and high-throughput sequencing, or cfMeDIP-seq. Where other liquid biopsy methods search for mutations in tumor-shed DNA that reveal the type and location of cancer, cfMeDIP-seq detects abnormal methylation — the addition of chemical tags to DNA, which doesn’t alter their genetic code but can affect their function.
The method was tested on samples from 99 patients with early and advanced kidney cancer, 15 patients with stage IV urothelial bladder cancer, and 28 healthy, cancer-free control subjects. In analyzing blood serum with the test, the study reported “near-perfect” classification of patients across all stages of kidney cancer. While urine-based classification was not as accurate, the study authors claimed that “performance can be improved through technical and computational optimization.”
Co-first authors of the report are Pier Vitale Nuzzo, Jacob E. Berchuck, Keegan Korthauer, and Sandor Spisak.
This study was conducted with support from Rebecca and Nathan Milikowsky, the Claudia Adams Barr Program for Innovative Cancer Research, the H.L. Snyder Medical Research Foundation, the Dana-Farber/Harvard Cancer Center Kidney SPORE and Program, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute.
"Utaratibu mpya wa ""biopsy"" unaweza kugundua saratani ya figo kwa usahihi mkubwa, ikiwa ni pamoja na uvimbe mdogo, ambao mara nyingi unaweza kutibiwa lakini ambao hakuna njia ya kugundua mapema, wanasema wanasayansi kutoka Taasisi ya Saratani ya Dana-Farber." Ripoti hiyo ya Nature Medicine inaonyesha kwamba ikiwa itathibitishwa katika majaribio makubwa na kutumika kwa wingi, jaribio hilo lisilo la uvamizi linaweza kupata saratani za figo mapema zaidi wakati hazijaenea, na hivyo kupunguza vifo vya ugonjwa huo. "Tuna matumaini tunaweza kuongeza kiwango hiki na kugundua saratani mapema ili tuweze kutenda mapema, "alisema Toni Choueiri, mkurugenzi wa Kituo cha Lank cha Oncology ya Genitourinary huko Dana-Farber na mwandishi mwenza wa utafiti huo." Inakadiriwa kuwa watu 73,750 watagunduliwa na saratani ya figo mwaka huu na 14,830 watakufa kutokana na ugonjwa huo. Asilimia 35 ya saratani huchunguzwa baada ya kuenea zaidi ya figo na ni vigumu kutibu. Kwa kawaida, uvimbe mdogo wa figo wa mapema hauleti dalili zozote, na mara nyingi hupatikana kwa njia ya bahati mbaya katika uchunguzi wa tumbo unaofanywa kwa kusudi jingine. Hata hivyo, hakuna uchunguzi wa picha au uchunguzi mwingine unaopendekezwa kwa watu kwa ujumla ili kutafuta kansa za figo za mapema. "Mwanzoni, mtihani unaotegemea njia iliyoelezwa katika ripoti hiyo mpya unaweza kutumiwa kuwahesabu watu wenye historia ya familia ya kansa ya figo au ambao walikuwa na kansa ya figo hapo awali,"" alisema Choueyri." "Tunahitaji kuwa maalum kwanza, kabla ya kuifanya kuwa ya kawaida kabisa", alisema. Biopsia ya kioevu isiyo ya uvamizi, ambayo inatafuta DNA inayohusiana na kansa iliyopitishwa na uvimbe katika damu au maji mengine ya mwili, inaendelea haraka kuelekea matumizi ya kliniki kama njia ya kugundua mapema kwa aina fulani za uvimbe. "Kansa ya figo ni moja ya uvimbe mgumu zaidi kugundua, kwa sababu haitoi DNA nyingi kama uvimbe mwingine", alisema Matthew Freedman, mtaalamu wa uvimbe wa matibabu katika Dana-Farber na mwandishi mwenza wa ripoti hiyo. "Mtihani huo unafanya kazi vizuri kwa sababu unaweza kutambua mifumo isiyo ya kawaida katika kiasi kidogo cha DNA ya uvimbe, "" Freedman aliongeza." "Hii ni uthibitisho wa kanuni kwamba ugonjwa wa hatua ya mapema unaweza kugunduliwa, ""aliongeza, ""mtihani huo ulikuwa karibu na asilimia 100 sahihi wakati ulitumiwa na sampuli za damu kutofautisha wagonjwa wenye kansa ya figo na wale wanaojulikana kuwa hawana kansa ya figo." Njia hiyo haifanyi kazi kwa usahihi kama ule wa sampuli za mkojo, lakini watafiti wanaamini kwamba inaweza kufanya kazi vizuri zaidi. Kama mtihani ni kuthibitishwa katika majaribio makubwa na inakuwa sana kutumika kliniki, sampuli ya mkojo itakuwa hata chini ya uvamizi kuliko damu kuchukua. Utafiti huo unaitwa Cell-Free Methylated DNA Immunoprecipitation and High-Throughput Sequencing (CfMEDIP-SEQ). "Wakati mbinu nyingine za ""biopsy"" zinachunguza mabadiliko katika DNA ya uvimbe ambayo hufunua aina na eneo la kansa, cfMEDIP-seq hupata ""methylation isiyo ya kawaida"" - kuongeza alama za kemikali kwa DNA, ambayo haibadili nambari yao ya maumbile lakini inaweza kuathiri kazi yao." Utafiti huo ulifanywa kwa kutumia sampuli za wagonjwa 99 walio na saratani ya figo ya mapema na ya hali ya juu, wagonjwa 15 walio na saratani ya kibofu cha mkojo ya urethral ya hatua ya nne, na wagonjwa 28 wenye afya, wasio na saratani. Katika kuchambua seramu ya damu na mtihani, utafiti uliripoti uainishaji wa "karibu kamilifu" wa wagonjwa katika hatua zote za kansa ya figo. Wakati uainishaji wa mkojo haukuwa sahihi, waandishi wa utafiti walidai kwamba "utendaji unaweza kuboreshwa kupitia uboreshaji wa kiufundi na wa hesabu". Waandishi wa kwanza wa ripoti hiyo ni Pier Vitale Nuzzo, Jacob E. Berchuck, Keegan Korthauer, na Sandor Spisak. Utafiti huo ulifanywa na Rebecca na Nathan Milicowski, Mfumo wa Claudia Adams Barr wa Utafiti wa Uvumbuzi wa Saratani, na HL. Snyder Medical Research Foundation, Dana-Farber Cancer Center Kidney SPORE na Programu, Kohlberg Chair katika Chuo cha Tiba cha Harvard na Trust Family, Michael Brigham, na Loker Pinard Funds kwa Utafiti wa Saratani ya Figo katika Taasisi ya Saratani ya Dana-Farber.