Research integrity investigators have identified a potential new red flag for fraudulent papers in cancer research: findings about human cell lines that apparently do not exist. A recent study examined eight cell lines that are consistently misspelled across 420 papers published from 2004 to 2023, including in highly ranked cancer research journals. While some misspellings might be inadvertent errors, a subset of 235 papers provided details about seven of the eight lines, suggesting that the reported experiments were not actually conducted.

"Unfortunately, this just looks like a massive invention of data and experiments that probably never happened," said study lead author Jennifer Byrne, a cancer researcher and data sleuth at the University of Sydney. Some of these nonexistent cell lines have already been cited in literature reviews, potentially misleading other scientists conducting similar studies. "It's a hell of a mess," she added.

Chao Shen, a cell biologist at Wuhan University and deputy director of the China Center for Type Culture Collection, a repository of human cell lines, emphasized the importance of these findings. "These revelations underline the urgent need for concerted efforts to address the challenges posed by [these] cell lines to research integrity and reproducibility," he said, advocating for standardized reporting of cell lines.

Issues with human cell lines have been a topic of concern in recent years, as many have been found contaminated by more robust lines, skewing results. However, this new study highlights a different issue: potential fabrication of cell lines.

Published last week in the International Journal of Cancer, the study began by investigating misspelled cell lines in cancer research papers to see if they were contaminated or misidentified. While some misspellings might have originated from inexperienced authors, Byrne and her team became suspicious of a subset of papers that repeatedly referred to the same seven cell lines as distinct from similarly spelled known lines. For instance, some papers reported different results from experiments using both the incorrectly and correctly spelled names of the same cell line.

These papers exhibited additional red flags: they lacked descriptions of how the suspicious cell lines were derived and did not provide the unique genetic fingerprints based on specific DNA sequences known as tandem repeats. Furthermore, several papers claimed that researchers could purchase these cell lines from three repositories, including the American Type Culture Collection, yet none of these lines were found in their directories.

The team ultimately identified 235 such papers in 150 journals, including high-impact publications like Cancer Letters and Oncogene. Most of the authors were affiliated with hospitals in China, a group previously identified as frequent clients of paper mills—businesses that sell authorship on often fraudulent or low-quality papers to those under pressure to publish for career advancement.

"It's difficult to prove unequivocally that something doesn’t exist," Byrne said, "but from our analyses, we’re pretty confident." She speculates that paper mill writers might have copied misspelled names from otherwise legitimate papers without knowing the correct spellings, rather than fabricating new names, which might have attracted more scrutiny. "The suspect characteristics are just really unlikely to be made by a genuine researcher," she noted. "I worked with cell lines 30 years ago, and I can still recite their names."

Byrne believes these papers might only be the tip of the iceberg. Since January 2023, over 50,000 scholarly articles about human cancer cell lines have been published. Her team identified a total of 23 misspelled lines but limited their analysis to eight mentioned in 420 papers to manage their workload. They plan further examinations and hope other researchers will join the effort. "We’re a small group, and going through these papers is very tedious," she concluded.

More: https://www.science.org/content/article/hundreds-cancer-papers-mention-cell-lines-don-t-seem-exist